WFSBP Abstract Book Final

The World Journal
of Biological Psychiatry
Volume 8
Supplement 1, 2007
Guest Editors
Frederick Goodwin, Jose Luis Ayuso-Gutierrez, Veronica Larach-Walters, Siegfried Kasper
2nd International Congress of Biological Psychiatry

April 17th - April 21st, 2007
Santiago, Chile
ABSTRACTS
The Official Journal of the World Federation

of Societies of Biological Psychiatry
The World Journal of Biological Psychiatry, Supplement 1, Vol 8, 2007
The World Journal of Biological Psychiatry

ISSN print edition 1562 - 2975
Founding Editors
Hans-Jrgen Mller (Germany)
Carlos Roberto Hojaij (Australia)
Joseph Zohar (Israel)
Chief Editor
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Department of Psychiatry
Ludwig-Maximilians-University
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Germany
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The Melbourne Institute of Biological
Psychiatry
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Chaim Sheba Medical Center
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Michael Bauer (Germany)
Robert H. Belmaker (Israel)
Graham Burrows (Australia)
Arvid Carlsson (Sweden)
Giovanni B Cassano (Italy)
Marcelo Cetkovich-Bakmas (Argentina)
Delcir da Costa (Brazil)
Frederick Goodwin (USA)
Jose Luis Ayuso Gutierrez (Spain)
Ralf P Hemmingsen (Denmark)
Eric Hollander (USA)
Florian Holsboer (Germany)
Lewis L Judd (USA)
Nobumasa Kato (Japan)
Martin B Keller (USA)
Yves Lecrubier (France)
Brian Leonard (Ireland)
Odd Lingjaerde (Norway)
Henri Loo (France)
Juan J Lopez-Ibor (Spain)
Mario Maj (Italy)
Herbert Y Meltzer (USA)
Julien Mendlewicz (Belgium)
Stuart Montgomery (UK)
David Nutt (UK)
Tatsuro Ohta (Japan)
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Hernan Silva-Ibarra (Chile)
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Costas Stefanis (Greece)
Dan J Stein (South Africa)
Saburo Takahashi (Japan)
Marcio Versiani (Brazil)
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Daniel Weinberger (USA)
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Table of Contents
FOREWORD ..................................................................4
OPENING LECTURE ......................................................5
PLENARY LECTURES ....................................................5
SYMPOSIA
Addictive Disorders ......................................................7
Affective Disorders (Bipolar)........................................10
Affective Disorders (Unipolar) ....................................11
Anxiety ......................................................................14
Childhood & Adolescent Disorders ............................17
Neurodegenerative Disorders......................................18
Psychotic Disorders ....................................................21
Brain Function ............................................................34
Genetics ....................................................................37
Neuroimaging ............................................................41
Psychopharmacology ..................................................45
Other ........................................................................52
FREE COMMUNICATIONS
Addictive Disorders ....................................................60
Affective Disorders (Bipolar)........................................62
Affective Disorders (Unipolar) ....................................64
Anxiety ......................................................................67
Childhood & Adolescent Disorders ............................69
Neurodegenerative Disorders......................................72
Psychotic Disorders ....................................................75
Brain Function ............................................................78
Genetics ....................................................................80
Neuroimaging ............................................................82
Psychopharmacology ..................................................84
Other ........................................................................86
POSTERS
Addictive Disorders ....................................................92
Affective Disorders (Bipolar)......................................100
Affective Disorders (Unipolar) ..................................104
Anxiety ....................................................................113
Childhood & Adolescent Disorders ..........................121
Neurodegenerative Disorders....................................126
Psychotic Disorders ..................................................135
Brain Function ..........................................................161
Genetics ..................................................................166
Neuroimaging ..........................................................171
Psychopharmacology ................................................181
Other ......................................................................205
SATELLITE SYMPOSIA ..............................................221

AUTHOR INDEX........................................................224
Foreword
Dear Colleagues,
The Scientific Program is considered the core of the 2nd International Congress of Biological Psychiatry. Thus the
International Scientific Program Committee is proud to have compiled a well balanced blend of Plenary Lectures,
Symposia, WFSBP Treatment Guidelines Workshops, Debates, Free Communications and Guided Poster Tours covering
all aspects of psychiatric disorders from basic to clinical reasearch including the newest concepts for improving the
patients lives.
As with all congresses of the World Federation of Societies of Biological Psychiatry (WFSBP), the Scientific Program greatly
depends on the submitted proposals and abstracts. In this sense we first would like to thank all Chairs, Co-Chairs and
Speakers who accepted with enthusiasm to participate and who will present high quality work. A WFSBP congress is not
possible without the continuing support from its National Societies of Biological Psychiatry. We cordially thank the WFSBP
National Societies for their engagement and for spreading the ideas that we are committed to.
In the last couple of years there has been radical progress in neuroscience that is changing our concepts and attitudes
on mental diseases. The advances in biology and molecular genetics, the availability of modern technologies such as
brain imaging, the development of a new generation of treatments based upon neuroplasticity concepts are opening
our field to new and exciting horizons. With this Scientific Program we will have the opportunity to discuss these themes as well as the integration between the rapid development of scientifc knowledge and its impact on diagnoses, treatment, and rehabilition of patients with mental disorders.
It is most special to us that the 2nd International Congress of Biological Psychiatry is held in Santiago de Chile. The
WFSBP has traditionally strong Latin American roots, especially through the first WFSBP President Edmund Fisher. Today,
exciting developments are taking place in Latin America, such as institutional reforms, increasing foreign direct investment and the recent surge in exports. In the field of psychiatry an increasing number of world renown Latin American
scientists are formative and influential. Therefore this congress is the ideal setting to share recent evolvements, exchange
thoughts with decision makers from all around the globe, and discuss the newest innovations in our field.
We believe that you will find interesting updates for new and better treamtent of your patients and fruitful thoughts for
your research work in this Scientific Program.
Yours sincerely
Dr. Frederick Goodwin

Co-Chair of the WFSBP International Scientific
Program Committee
Prof. Jose Luis Ayuso-Guitierrez

Co-Chair of the WFSBP International Scientific
Program Committee
Prof. Siegfried Kasper

Congress President
President World Federation of Societies
of Biological Psychiatry
Opening/Plenary Lectures
Opening Lectures
O-01
Opening Lecture: Lost and found in translational research: The challenge and promise
T12 Other
O-01-01
Lost and found in translational research: The challenge and
the promise
Raquel Gur
University of Pennsylvania, Psychiatry, Philadelphia, USA
There has been increased focus on developing paradigms that enhance
translational research. In complex disorders these efforts mandate interdisciplinary collaborations. Two links are essential for such a bridge, one
between basic and clinical neuroscience research and the other between
clinical research in an academic setting to clinical practice in the field.
Such translational paradigms will be exemplified with schizophrenia. The
challenge is to zoom in on a theme and develop a research plan that
can test complementary hypotheses in humans and animal models. What
can be lost in the first link is the limitation of comparing human behavior
to that modeled in basic studies. The pitfalls of linking academic research
to clinical settings are in loosing sight of the diversity of individuals affected and the complexity of their environment. These dangers are especially
noteworthy because the range of available tools and the required expertise lead to narrowing the scope of the research.
Plenary Lectures
PL-02
Ethics and neuropsychiatry
T12 Other
PL-02-01
Ethics and neuropsychiatry
Fernando Lolas Stepke
University of Chile, Pan American Health Org., Santiago, Chile
This lecture addresses current issues in neuropsychiatric research in the
context of Western ethical traditions, teleology and deontology. It is
argued that contemporary bioethical thinking, by creating the social institution of the committee, uses dialogue and deliberation for the formulation, justification, and resolution of dilemmas arising from scientific
progress and its applications to human affairs. Research is examined from
the standpoint of its technical or instrumental value, its scientific or theoretical importance, and its social or hermeneutic relevance. In each realm,
ethical considerations are essential to achieve integration between values
related to the search for truth, to the enhancement of knowledge and to
the improvement of the human condition. Several areas are identified: the
impact of neuroscientific information on conceptions about the human
brain and its performance, the biological foundations of moral/social
behaviour, the conceptual nervous systems underlying different philosophical theories about human life, among others. As the application of
neuroethics extends beyond laboratory and experiment, other aspects
acquire relevance, such as the ethics of mind-enhancing drugs or interventions, the links between psychological and biological methods on
behaviour and mentation, and the accessibility of knowledge to people in
different parts of the world or diverse social conditions. As a third area of
inquiry, the ethics of neuroscientific research is singled out in some of its
characteristic features and its importance in the training of researchers
and practitioners.
PL-01
Is cyclicity or polarity more fundamental to the
classification of mood disorders?
PL-03
Neurobiology and treatment of cannabis
dependence
T2 Affective Disorders (Bipolar)
T9 Genetics
PL-01-01
Is cyclicy or polarity more fundamental to the classification of major mood disorders?
PL-03-01
Neurobiology and treatment of cannabis dependence
Frederick Goodwin
George Washington Univ., Medical Center, Bethesda, MD, USA
Kraepelins description of manic-depressive illness encompassed all major
recurrent mood disorders. Subsequent investigators, principally Leonhard,
Perris, Angst and Winokur subdivided manic-depressive illness into unipolar and bipolar based on the presence or absence of a prior history of
mania. The NIMH group (Dunner, Gershon and Goodwin) subsequently
subdivided the bipolar group into BP I and BP II based, respectively, on a
history of mania vs hypomania only. Like Kraepelin, the original UP-BP
distinction was based on studies of patients with recurrent affective disorders. Notwithstanding this history, the architects of DSM III and IV separated out bipolar disorder from the top, explicitly making polarity the
primary basis for organizing the mood disorders. This presentation will
examine both the reasons for this fundamental shift in the evolution of
the DSM system and the evidence supporting Kraepelins original emphasis on the importance of recurrence across the affective spectrum.
David A. Gorelick
National Institute on Drug Abuse, Baltimore, USA
Introduction: Cannabis is the most widely used illegal drug in the world,
with an estimated 160 million current users. Community-based epidemiological studies suggest that about 10% of users develop dependence.
The psychoactive effects of cannabis are primarily due to activation of
cannabinoid CB1 receptors by THC. The endogenous ligands for this
receptor include fatty acid derivatives such as anandamide (arachidonylethanolamide) and 2-arachidonoylglycerol (2-AG), which appear to
function as retrograde modulators of synaptic neurotransmission.
Plenary Lectures
Method: There are no proven, broadly effective medications for the treatment of cannabis dependence, and no medication is approved by any
regulatory authority for this indication. Treatment generally involves psychosocial methods, such as cognitive behavioral therapy and motivational
enhancement. Many cannabis users are adolescents, in which case family
involvement in treatment is essential. Many cannabis users have psychiatric comorbidity, the treatment of which may also be helpful in reducing
cannabis use. Both self-report studies and human experimental studies
indicate that chronic cannabis use can result in physical dependence and
a withdrawal syndrome.
Results: A retrospective survey of 104 adult cannabis smokers found that
70% experienced at least 3 withdrawal symptoms during their quitting
attempt (Copersino et al., 2006). A majority (56%) reported taking action
to relieve withdrawal symptoms, including some who resumed cannabis
use, indicating that withdrawal can be a negative reinforcer for relapse.
One treatment approach under study is blockade of CB1 receptors by
rimonabant. This medication blocks the acute psychological and cardiovascular effects of a smoked cannabis cigarette, without altering THC
pharmacokinetics (Huestis et al., 2001). Other medications under study
include buspirone, baclofen, quetiapine, and substitution treatment with
oral THC.
Conclusion: Cannabis use produces physical dependence in humans;
treatment of withdrawal symptoms may reduce relapse. Several medications, including the CB1 antagonist rimonabant, are under study as possible treatments for cannabis dependence.
References: Copersino et al., Am J Addict 15:8-14, 2006. Huestis et al.,
Arch Gen Psychiat 58:322-328, 2001 Acknowledgment: Research supported by the Intramural Research Program, NIH, NIDA and Sanofi-Aventis
(studies with rimonabant).
PL-04
Biological psychiatry integrated in clinical
science
T12 Other
PL-04-01
Biological psychiatry integrated in clinical science
Siegfried Kasper
Medical University, General Psychiatry, Vienna, Austria
Based on the sound knowledge of clinical psychiatry neuroscientists
embark since over 20 years to discover the biological bases of mental disorders. Whereas the window to the brain was firstly dominated by neuroendocrine and biochemical models, we now have the possibility to use
sophisticated brain imaging techniques which span from electrophysiology
to techniques derived from nuclear medicine. Furthermore, the combination of brain imaging techniques with genetic variables promises to have
a close insight into brain-environment interactions. For treatment of psychiatric diseases, multidimensional criteria for selection of a psychotropic
medication is necessary to not only judge the clinical phenotype but also
the functional phenotype and finally the genotype. Whereas the clinical
phenotype is characterized by psychiatric syndromes including psychiatric
and somatic comorbidity, the functional phenotype can be uncovered
with neuroendocrine measurements, sleep physiology, imaging techniques as well as proteomics. Finally, the genotype can be characterized
by single nucleotid polymorphisms (SNP), coupling as well as the determination of candidate genes. Imaging genetics is a new way to achieve
insight in the genetic variables of changes on a cellular level which thereafter influence information processing and finally are represented in complex functional interaction of human behavior. Based on this knowledge
it is evident that psychiatrists not only should be determined to the clinical symptomatology of their patients but also on the underlying biological processes which can in turn be influenced to various degress with
pharmacological as well as non-pharmacological treatment modalities.
ADDICTIVE DISORDERS - Symposia
Symposia
S-04
Comorbidity between substance use and
mental health disorders
T1 Addictive Disorders
S-04-01
Genetics of comorbid substance use and psychiatric disorders
James L. Kennedy
University of Toronto, Ctr. Addiction & mental Health, Canada
Julien Renou, Bernard LeFoll
Introduction: Smoking behavior is inflenced by both genetic and environmental factors. Genetic and pharmacologic studies have suggested
the alpha-7 nicotinic receptor gene (Deluca et al, 2004) and the
Dopamine Receptor D3 (DRD3) involvement in smoking behavior, which
are expressed in brain structures (eg nucleus accumbens) implicated in
drug dependence.
Method: We investigated the association between 10 DRD3 polymorphisms and smoking behavior in a cohort of 236 Caucasian schizophrenic
patients (155 smokers and 81 non-smokers). Our sample included
172 males and 64 females. The comparisons of the frequencies of genotypes and alleles in smokers and non-smokers for each polymorphism
were performed with contingency tables. Homozygosity versus heterozygosity was also tested using chi-square. Bonferoni correction for multiple
testing was used when applicable.
Results: The distribution of genotypes were in accordance with Hardy
Weinberg equilibrium. We did not find significant differences between
schizophrenia smokers and non-smokers in allele or genotype frequencies
for each polymorphism (p > 0.05). Smoking frequencies for males (72%)
and females (50%) populations differed significantly (2=11.58,
p=0.0007). Consequently, we also analysed DRD3 polymorphisms stratifying by gender. For male and female populations, no statistical differences were found in the genotype distributions or allele frequencies
between smokers and non-smokers (p > 0.05).
Conclusion: We conclude from our studies thus far, that the DRD3 gene
is not associated with smoking in our population of schizophrenic
patients. We have not yet performed interaction studies between DRD3
and the alpha-7 nicotinic subunit gene or the brain-derived neurotrophic
factor (BDNF) gene, each of which has rationale for involvement in
comorbid smoking behavior.
S-04-02
Comorbidity between bipolar and alcohol use disorder:
Genetic and environmental factors
Usoa Busto
CAMH, Neuroscience, Toronto, Canada
Baseer Yasseen, James Kennedy, Laurie Zawertailo
Introduction: Bipolar Disorder (BP) has high rates of comorbidity with
substance use disorders. Frequency of alcohol use disorders has been
found to be 9 times more prevalent in BP than in the general population
(1).
Method: In a secondary analysis of data from the Toronto Bipolar
Disorders database (N=295) the demographic characteristics, environmental factors and the genetics of the comorbid disorder were determined.
We hypothesize that alleles for the candidate genes (5HT2A, 5HT1Db,
5HTT and DRD3) will be more prevalent in comorbid BP patients compared
to non-comorbid BP.
Results: Results show that patients had a mean age of 42.8 with a range
from 22 to 87 years, 63% females; and 80% high school graduates.
There were gender differences between males and females: females were
significantly more likely to be married (p< 0.008) and have family conflicts
than males (p< 0.006) but males had a higher frequency of alcohol use
disorders (36.3%) than females (19.1%; p< 0.001). Comparison between
comorbid and non-comorbid groups of allele frequencies of the 4 candidate genes showed that there was a significantly higher frequency
(p<0.04) of the C allele in 5HT2A in BP and alcohol use disorder
patients compared to non-comorbid patients. The allele containing 12
repeats in the VNTR region of the 5HTT was significantly more prevalent
in comorbid than non-comorbid patients (p<0.0007). There was no association between DRD3 alleles and comorbidity.
Conclusion: Patients with comorbid BP and alcohol use disorders may
share a genetic predisposition to develop these disorders possibly due to
alterations in the neurotransmitters and receptors associated with BP and
alcohol use disorders.
References: 1. Kessler R, McGonagle K, Zhao S et al: Lifetime and 12month prevalence of DSM-III-R psychiatric disorders in the United States:
Results from the National Comorbidity Survey. Archives of General
Psychiatry 1994;51:8-19
S-04-03
A dimensional view of monoamines and the regulation of
mood and motivational states: Implications for co-morbid
psychiatric disorders
Marco Leyton
McGill University, Psychiatry, Montreal, Canada
Introduction: Recent studies suggest that individual differences in serotonin and dopamine neurotransmission correspond to continuums of personality traits and vulnerability to pathological behaviors and psychiatric
disorders. High mesolimbic dopamine function might enhance tendencies
toward focused approach, novelty seeking, persistence, and optimistic
cognito-affective states. Low dopamine, in comparison, might disrupt the
ability to sustain focus, increase susceptibility to impulsivity and lack of
persistence, and affect susceptibility to pessimistic states. Low serotonin,
in turn, might increase susceptibility to impulsive-aggression, labile mood
regulation, and low social rank.
Method: To investigate these associations further, we have been using
functional neuroimaging and biogenic amine precursor depletion methods
in a range of populations.
Results: Preliminary studies suggest that subjects who are at risk for
impulsive, aggressive behaviors exhibit evidence of reduced serotonin synthesis (low alpha-[11C]methyl-tryptophan trapping) in the orbitofrontal
cortex. Individual differences in a[11C]MTrp trapping throughout limbic
cortico-striatal pathways correlate with impulsive responding on a Go/NoGo task. Experimentally reducing serotonin synthesis, using acute tryptophan depletion, increases impulsive responding and lowers mood, and
these effects are greater in vulnerable populations. Recent studies suggest
that dopamine may also contribute to some of these same behaviors.
Individual differences in the personality trait of novelty seeking predict differences in amphetamine-induced striatal dopamine release and susceptibility to drug-induced sensitization. In comparison, acute depletion of the
dopamine precursors, phenylalanine and tyrosine, increases impulsive
behavior, particularly in response to cues that predict reward, decreases
focused craving and the ability to sustain motivation during a progressive
ratio alcohol self-administration task, and aggravates the mood-lowering
response to a social stressor. Finally, a very recent study suggests that
acute tryptophan depletion increases the striatal dopamine response to
intra-nasal cocaine.
Conclusion: Together, these results raise the possibility that pre-existing
traits of low serotonin and dopamine tone are associated with impulsive,
aggressive, emotionally volatile behaviors as well as disinhibited dopamine
responses to psychostimulant drugs. Collectively, these features might
account, in part, for an overlapping vulnerability to a range of co-morbid
psychiatric disorders.
S-04-04
Comorbid major depression and tobacco dependence:
Neurobiology and behaviour in humans
years we have seen the development of dependence on coca leaf chewing that requires a deeper study to determine its health and political consequences.
Laurie Zawertailo
CAMH, Clinical Neuroscience, Toronto, Canada
Vlad Kushnir, Usoa Busto
S-14-02
Developing treatments for cannabis dependence
Introduction: Chronic use of tobacco may induce neuroadaptations.

Preclincal studies suggest that neuroadaptations induced by repeated
drug use involve altered neurotransmission and brain metabolism as well
as changes in behavioural and attentional processes triggered by specific
drug-related stimuli. It is not known whether these changes are different
in individuals with comorbid tobacco dependence and major depression.
We will present two recent neuroimaging studies that measured neural
changes in smokers compared to control subjects, with and without a
current diagnosis of major depressive disorder (MDD).
Method: In Study 1 we measured [11C]-raclopride (RAC) binding to
dopamine D2 receptors using PET, both prior to and 2-hours following
single-blind oral administration of 30mg d-amphetamine, in four different
subject groups: non-smokers (n=11); smokers (n=10); MDD non-smokers
(n=11) and MDD smokers (n=9). Subjective effects of amphetamine were
measured during the PET scan using visual analog scales (VAS). In Study 2,
we investigated the neural correlates of craving in never-smokers (i.e. less
than 100 cigarettes/lifetime) (N=4), current smokers in withdrawal (N=4)
and past smokers in early remission (i.e. <6 months remission) (N=4) using
auditory and visual cues during functional magnetic resonance imaging
(fMRI).
Results: In Study 1, there was a main effect of smoking on amphetamine-induced RAC displacement where smokers had significantly less displacement compared to non-smokers (p<0.002). Comorbod subjects had
signficantly less binding comared to control non-smokers (p<0.03) and
MDD non-smokers (p<0.01). Subjectively, smokers reported positive subjective effects similar to non-smokers but had significantly higher scores
on negative subjective effects (p<0.01). These results suggest that chronic
smokers have an altered dopaminergic system compared to non-smokers.
In Study 2, nicotine deprived current smokers and former smokers in early
remission exhibited similar neural responses to visual smoking cues in
well-defined regions (ventrolateral and dorsolateral prefrontal cortex,
amygdala) relative to never smokers. Subjective measures of craving,
however, showed that only current smokers deprived of nicotine reported
significant craving using the Questionnaire of Smoking Urges (QSU) than
both past smokers in early remission and never smokers.
Conclusion: These results suggest that neurochemical differences exist in
comorbid individuals compared to individuals with a single disorder. Also,
nicotine-induced neuroadaptations persist following cessation and neural
reactivity to smoking cues may occur without conscious awareness. These
preliminary findings may have implications for tobacco craving and
increased vulnerability to relapse in comorbid individuals.
S-14
Treatment options in drug and behavioral
addictive disorders
S-14-01
Treatments for different forms of cocaine dependence
Nils Noya-Tapia
Postgraduate School in Psychiatry, Santa Cruz, Bolivia
The consumption of cocaine in the world has increased in the last years.
The diverse routes of administration by which cocaine is consumed, like
the basic cocaine paste and crack cocaine, and their association with
other abused drugs or alcohol has also increased. There is also the possibility of incremental cerebral damage from cocaine use that might be irreversible. These facts gave a very poor prognosis for many patients. Until
now, there is not a pharmacological treatment that has been completely
successful. New medications under study include modafinil, anti-convulsants such as topiramate, and an anti-cocaine vaccine. During the last
David A. Gorelick
National Institute on Drug Abuse, Baltimore, USA
Cannabis is the most widely used illegal drug in the world, with an estimated 160 million current users. Treatment generally involves psychosocial methods, such as cognitive behavioral therapy and motivational
enhancement. Many cannabis users are adolescents, in which case family
involvement in treatment is essential. No medication is approved for treatment of cannabis addiction. Medications under study include rimonabant, a cannabinoid CB1 receptor antagonist, and substitution treatment
with oral THC, the primary psychoactive chemical in cannabis. Many
cannabis users have psychiatric comorbidity, the treatment of which may
also be helpful in reducing cannabis use.
S-14-03
How genetics can guide the development of treatments for
alcoholism
Peter Dodd
University of Queensland, Molecular Biosciences, Brisbane, Australia
There are substantial individual differences in alcohol craving, severity of
alcohol withdrawal, propensity for alcohol dependence and alcoholinduced brain damage. Some of this variability is due to genetics: most
current estimates of the heritability of dependence are in the range 5060%. Genetic control of neurotransmitter receptor subunit composition
in the brain, and of programmed cell death (apoptosis), may contribute
to an individuals liability to or protection from alcohol dependence and
its consequences. Identification of specific relevant alleles will help guide
development of new, more precisely targeted prevention and treatment
medications. We have investigated genotype-phenotype interactions by
studying GABA-A and glutamate-NMDA receptor subunit expression in
autopsy tissue extracts from well-characterized alcoholics with and without comorbid disease, and matched controls. Tissue samples were taken
from superior frontal cortex, which is highly vulnerable to neuronal cell
death in alcoholics, and primary motor cortex, which is relatively spared
in this regard. Subjects were genotyped on a range of markers that have
been associated with alcohol misuse and dependence in literature
reports. Expression was measured with a range of techniques: levels of
subunit mRNA transcripts were quantified by competitive reverse-transcription PCR or by Real Time reverse-transcription PCR; amounts of subunit proteins were assayed by immunoblotting; and receptor densities
were quantified by pharmacological binding assays. A limited number of
genotypes modulated receptor subunit expression and density. For example,
SLC1A2G603A, GABRB2C1412T, and 5HTTLPR genotypes mediated
glutamate-NMDA receptor expression, most notably in female alcoholics
with cirrhosis. In contrast, there were significant, regionally selective,
interactions of DRD2B1, SLC1A2G603A and APOE3 genotypes with
GABA-A receptor beta-subunit protein expression when alcoholics without comorbid disease were compared with controls. In each of the latter
instances, possession of the alcoholism-associated allele increased the
beta-2 to beta-3 ratio in the pathologically vulnerable region, a response
that would be likely to reduce inhibitory tone and hence promote local
excitotoxicity. Since subunit composition controls receptor pharmacology,
these and similar data will underpin the development of novel therapeutics that can be exquisitely targeted to the most vulnerable cells. As well,
the data will guide the counselling of individuals who may be at greater
risk of alcohol-induced brain damage as a consequence of their genetic
make-up. Supported by the National Institutes of Alcoholism and Alcohol
Abuse (USA) under grant NIH AA12404 and the National Health and
Medical Research Council (Australia) under grant #981723.
S-14-04
Genetics and treatment of pathological gambling: Who
will benefit from pharmacological treatment?
James L. Kennedy
University of Toronto, Ctr. Addiction & Mental Health, Canada
Daniela S.S. Lobo, Sahar Ethesdam, Nicole King, Joanne Brathwaite,
Nigel Turner
Pathological gambling (PG) is considered to be a behavioural addiction,
sharing clinical similarities with substance addiction. Addictive behaviours, including PG, are characterized by the engagement in a repetitive
behavioural pattern (repetitive drug-seeking/ drug taking, repetitive gambling) despite its evident negative consequences. The incentive-sensitization theory hypothesizes that the dysfunctional behavioural pattern in
addictions is the result of neuroadaptations that sensitize the brains
reward system to drugs and to drug-associated cues. There has been
mounting evidence that gambling can promote priming-like effects in
problem gamblers. For instance, it has been found that exposure to a
brief episode of gambling is associated with increased desire to gamble
and decreased control over gambling in problem gamblers compared to
control subjects. These studies provide experimental evidence that gambling can promote sensitization-like effects and that psychostimulant-like
neurochemical activation underlies these effects in problem gamblers.
According to the most recent findings on the neurobiology of psychostimulant action sites and decision-making processes, polymorphisms on the
COMT, BDNF and dopamine system genes have been found to have an
impact on frontal lobe executive function and amphetamine response,
presumably trough promoting a change on dopamine availability. Better
understanding of the processes underlying sensitization could have paramount implications on treatment and relapse prevention. Clinical trials
have found that PrG present some response to SSRIs, opioid antagonists
and mood stabilizers. However, findings regarding decision making and
amphetamine effects on PrG raise the possibility that PrG could respond
better to drugs that increase synaptic dopamine, such as dopamine transport inhibitors, as opposed to SSRIs. Our group has found an association
of PG with the blunted response variants (D4.2 and D4.7) of DRD4. The
dopamine D3 receptor gene is a promising drug target due to its expression in areas of the brain that are closely related to behavioural and substance addictions. We will present evidence of the association of PrG in
females with polymorphisms in this gene. Being able to predict drug
response through the genotypes of PrG could result in a better time and
cost-effective treatment.
AFFECTIVE DISORDERS (BIPOLAR) - Symposia
S-49
Advances in the management and treatment of
the bipolar disorder
S-49-01
General health status in bipolar disorder patients under
treatment
Julio Bobes
Oviedo, Spain
Introduction: Bipolar disorder is a highly prevalent and disabling condition
with greater medical comorbidity and mortality rates than in the general
population. This study evaluates the prevalence of metabolic syndrome
(MetS) and ten-year fatal cardiovascular (CVM) risk in a group of
142 Spanish patients with bipolar disorder.
Method: Bipolar patients (ICD-10 criteria) from 11 centres in Spain were
assessed cross-sectionally for MetS according to the NCEP ATP III criteria
and for ten-year CVM risk using the SCORE function.
Results: The mean age was 47.3 (SD 14.5); 51.1% were male. On average, patients were receiving 2.8 (SD 1.3) drugs for treatment of their
bipolar disorder. Ninety-one percent were receiving mood stabilizers,
63.4% antipsychotics, and 29.6 antidepressants. The overall prevalence
of MetS was 24.6% Fifty-seven percent of the sample met the criterion
for abdominal obesity, 37.4% for met the criterion for hypertriglyceridemia, 36.4% for low HDL-cholesterol, 25.2% for high blood pressure
and 12.5% for high fasting glucose. No statistically significant difference
was found between with and without MetS for gender, illness status
(acute versus in remission), CGI-S-BP scores and number of medications
used. Ten-year CVM risk was 1.62% (5.6) in women and 2.51% (4.3) in
men. This risk significantly increased with age in both sexes.
Conclusion: The prevalence of MetS in bipolar patients is high as well as
it is ten-year CVM risk. Clinicians should be aware of these issues and
monitor patients with bipolar disorder for these conditions as part of the
standard care for these patients.
S-49-02
Silvia Gaviria
Columbia
10
S-49-03
Valproic acid-induced hyperammonemia: Data, neurocognition and treatment
Eduardo Correa
Universidad de Chile, Clinica Psiquiatrica Univ., Oviedo, Chile
F. Herrera, A. Ortega, J.C. Martinez, F. Ivanovic-Zuvic, L. Risco
Hyperammonemia, one of the clinical expressions of hepatological disease,
can be observed as a secondary effect from the use of valproic acid. It
usually appears without presenting any hepatic function alteration, and it
is observed in almost half of the patients who receive this drug. In spite
of this, most patients remain apparently asymptomatic, without evidencing encephalopathy or they can present a slight compromise in cognitive
functions such as attention and memory, leading to a negative influence
on treatment adhesion. First we review published data in neurology (1),
then we have done several trials where we found a negative cognitive
impact of frequent high ammonia levels in bipolar patients, never studied
before (2,3,4). This secondary hyperammonemia has a very well documented management, where most of the patients can improve the
ammonium plasmatic values, without the necessity to suspend the use.
We had made, until we know, the first standardized trial with adult psychiatric patients, using oral L-carnitine. We suggests that there is a frequent, poor known problem with valproic acid use, we show our neurocognition data and the effectiveness of L-carnitine in reducing hyperammonemia
References: 1) Martinez JC, Correa Eduardo. Hiperamonemia secundaria
a Acido Valproico. Trast Animo 2006; 2 (1):34-43 2) Herrera F, Correa E,
Velsquez V. Neurocognicion en hiperamonemia inducida por acido valproico: efecto del tratamiento con L- carnitina. Trast Animo 2006; 2
(2):113-120 3) Correa E, Ortega A, Risco L, Ivanovic-Zuvic F. Prueba del
trazo en bipolares con hiperamonemia secundaria a acido valproico. 4)
Ortega A, Correa E, Risco L, Ivanovic-Zuvic F. Estudio de una paciente con
hiperamonemia secundaria a cido valproico utilizando bateria neuropsicoligica flexible.
S-49-04
Anthony Levitt
Canada
AFFECTIVE DISORDERS (UNIPOLAR) - Symposia
S-10
Muscarinic receptors in depression- a promising old hypothesis
S-10-02
Muscarinic 2 receptor abnormalities in bipolar disorder
T3 Affective Disorders (Unipolar)
Introduction: Using PET and [18F]FP-TZTP, we previously found that

depressed unmedicated subjects with bipolar disorder (BD), major depressive disorder (MDD), and of healthy controls (HC) revealed lower distribution volume (DV) of the M2-receptor in the BD group (Cannon et al.
2006. Arch Gen Psychiatry 63:741-7). Other studies had reported that
multiple M2-receptor polymorphisms were associated with an increased
risk for developing depression. We hypothesized that reduced M2-receptor binding in BD may be caused by a polymorphism in the gene coding
for the M2-receptor.
Method: In 23 HC, 16 BD and 16 MDD subjects who underwent [18F]FPTZTP PET scanning we genotyped six single nucleotide polymorphisms
(SNPs) not in high linkage disequilibrium (LD) with one another, in the
m2-gene. We used independent samples t-test and nonparametric correlations to assess relationships between genotype and regional DV of the
M2-receptor.
Results: We observed a dose effect of haplotype in several regions where
the T/T-genotype (rs324650) was associated with higher M2-receptor DV:
subgenual (r=0.522, p=0.011) and pregenual anterior cingulate cortices
(ACC; r=0.538, p=0.008), amygdala (r=0.428, p=0.042), and ventral
striatum (r=0.433, p=0.039). This effect accounted for 18-29% of the
variance in HCs. By contrast, BD subjects showed lower M2-receptor DV
with the T/T-genotype (n=6) than with A/A+A/T-genotypes (n=10) in hippocampus (p=0.042) and amygdala (p=0.045) and trended toward being
lower in subgenual (p=0.067), and pregenual ACC (p=0.076).
Conclusion: Preliminary evidence appears to show that in BD, reduced
M2-receptor DV is associated with the rs324650 polymorphism of the
M2-receptor gene, or with a variant in LD with this polymorphism.
Additionally, the fact that the polymorphism in the M2-receptor affects
the BD group differently from controls suggests an as yet unidentified
interaction with a vulnerability factor for BD.
S-10-01
Antidepressant effects of scopolamine in major depressive
disorder patients
Maura Furey
NIMH/NIH, Bethesda, Maryland, USA
Introduction: The cholinergic neurotransmitter system is implicated in
the pathophysiology of mood disorders. Increasing cholinergic activity
provides a challenge uniquely capable both of exacerbating symptoms in
currently depressed MDD patients, and inducing depressive symptoms in
manic bipolar (BD) patients (1,2). Evidence further suggests that the
cholinergic muscarinic receptors in particular are hyper-responsive in
depression (3,4). We evaluated the contribution of the cholinergic system
to depressive symptoms in MDD and BD patients by administering the
antimuscarinic, scopolamine.
Method: Eighteen depressed MDD and BD subjects participated in a double-blind, placebo-controlled, cross-over study. In each of 7 sessions, psychiatric evaluations were obtained using the Montgomery & Asberg
Depression Rating Scale (MADRS) and Hamilton Anxiety Rating Scale
(HARS) prior to a 15-min i.v. infusion of either placebo, or 4.0 g/kg of
scopolamine. After a single-blind, placebo lead-in session (providing
2 baseline measures) subjects were randomized into either a P/S or S/P
sequence where P constitutes a block of 3 placebo sessions and S a block
of 3 scopolamine sessions. Telephone follow-up evaluations were
acquired after session 7. Repeated measures ANOVA was used to assess
group X study phase X repeated assessment effects; between and within
group t-tests were used in planned comparisons.
Results: Repeated measures ANOVA showed a significant group
X assessment interaction (p< 0.0001). The 3-way ANOVA (group X study
phase X assessment) was significant (p= 0.005). The P/S group showed no
change from baseline during the placebo block, and reductions in MADRS
(p< 0.0001) (fig1A) and HARS (p< 0.0001) (fig1B) scores during the subsequent scopolamine block. The S/P group also showed reductions from
baseline in MADRS (p<0.0001) and HARS (p<0.0001) during scopolamine,
effects that persisted during the subsequent placebo block. Improvement
was significant at the first evaluation following scopolamine (p< 0.002).
No difference in the magnitude of change in MADRS
(p= 0.98) or HARS (p= 0.36) scores occurred based on diagnosis.
Conclusion: These results demonstrate rapid, robust antidepressant
responses to the antimuscarinic, scopolamine. Patients with MDD and BD
responded similarly. These results provide a strong link between the
cholinergic muscarinic receptors and mood disorders, and offer a new direction for effective treatment.
References: 1. Janowsky et al. Psychosomatic Medicine 1974.
2. Janowsky et al. Lancet 1972. 3. Gillin et al. Psychiatry Research 1979.
4. Kasper et al. Pharmacopsychiatria 1981.
Dara M. Cannon
National Institute of Mental Health, Neurobiology of Mood Disorders, USA
S-10-03
Impact of M1 and M2 muscarinic receptor functioning on
REM sleep regulation in healthy volunteers, implications
for depression
Christoph Nissen
Universittsklinikum Freiburg, Psychiatrie und Psychotherapie, Germany
Bernd Feige, Dieter Riemann, Mathias Berger
Introduction: Broad evidence from pre-clinical and clinical research indicates that cholinergic neurotransmission contributes significantly to the
generation of rapid eye movement (REM) sleep. However, a potential role
of different acetylcholine receptor (AChR) subtypes for the regulation of
three main aspects of REM sleep, (1) REM sleep onset, (2) REM sleep
maintenance and (3) generation of rapid eye movements, are not clear.
Method: In the present double-blind, randomized and placebo-controlled study, we investigated the differential effects of the M1 muscarinic
AChR agonist RS-86 and the ACh-esterase inhibitor donepezil to further
specify the AChR subtype function on REM sleep regulation in n=20
healthy volunteers.
Results: We found that RS-86 selectively shortened REM latency (MANOVA post-hoc contrast p=0.024 compared to placebo, not significant for
donepezil) and that donepezil specifically enhanced the duration of REM
11
sleep (% sleep period time, p=0.000 compared to placebo; p=0.003 compared to RS-86) and the number of REMs (p=0.000 compared to placebo; p=0.000 compared to RS-86).
Conclusion: These results provide evidence that the onset of REM sleep
is, in part, mediated by M1 mAChR activity whereas the maintenance of
REM sleep and the number of REMs are mediated by non-M1, but presumably M2 mAChR activity. The findings are discussed in the context of
REM sleep abnormalities in depression.
S-10-04
M1 muscarinic acetylcholine receptor agonism alters sleep
without affecting memory consolidation
Mathias Berger
Germany
Christoph Nissen, Ann E. Power, Bernd Feige, Ulrich Voderholzer, Dieter
Riemann
Preclinical studies have implicated cholinergic neurotransmission, and
specifically M1 muscarinic acetylcholine receptor (mAChR) activation, in
sleep-associated memory consolidation. In the present study, we investigated the effects of administering the direct M1 mAChR agonist RS-86 on
pre-post sleep memory consolidation. Twenty healthy human participants
were tested in a declarative word-list task and a procedural mirror-tracing
task. RS-86 significantly reduced rapid eye movement (REM) sleep latency
and slow wave sleep (SWS) duration in comparison with placebo. Pre-sleep
acquisition and post-sleep recall rates were within the expected ranges.
However, recall rates in both tasks were almost identical for the RS-86
and placebo conditions. These results indicate that selective M1 mAChR
activation in healthy humans has no clinically relevant effect on pre-post
sleep consolidation of declarative or procedural memories at a dose that
reduces REM sleep latency and SWS duration.
S-21
Genetic polymorphisms in anxiety disorders
and depression; Recent findings
S-21-01
Are genetic polymorphisms involved in antidepressant
treatment response?
Gianpaolo Perna
Via Stamira dAncona, Italy
Daniela Caldirola, Massimiliano Grassi, Laura Bellodi
While pharmacotherapy with antidepressants is an effective treatment of
depression and anxiety disorders, the outcome of drug therapy it still is
hampered by a delayed time of onset of clinical improvement and is often
unpredictable, ranging from beneficial effects to lack of efficacy to serious
adverse effects and a several side effects. Among the factors influencing
the interindividual variability in response to treatment with antidepressants, differences in genetic features play a significant role. Variations in
single genes are one well-recognized cause of such unpredictability,
defining the field of pharmacogenetics. Such variations may involve genes
controlling drug metabolism, drug transport, disease susceptibility, or
drug targets. Several genetic polymorphisms have been associated with
therapeutic response to antidepressants in mood and anxiety disorders,
including genetic variants of the 5-HT transporter, tryptophan hydroxylase,
catechol-O-methyltransferase, brain-derived neurotrophic factor, interleukin-1beta although with conflicting results; also cytochrome P450
drug-metabolising enzymes may be of a particular importance. The hope
is that the identification of these genetic components will eventually facilitate the development of a customised treatment with antidepressants.
The promise is to improve new drugs and ultimately individualizing the
selection of appropriate drugs and dosages for each individual patient.
12
S-21-02
Influence of the serotonin transporter gene on bipolar disorder and suicidal behaviour
Vincenco Deluca
Centre for Addiction and Mental Health, Toronto, Canada
James L. Kennedy
Introduction: A serotonin transporter gene linked polymorphic region
polymorphism (5-HTTLPR) has been investigated in several genetic association studies, including studies of bipolar disorder (BD) and suicidality.
Method: This study was designed to examine whether the new A/G variant polymorphism of the 5-HTTLPR region may be associated with the suicide attempts in 305 families with at least one member having BD.
Results: No association with history of suicide attempt was found either
in the multiallelic HTTLPR (LRS = 0.15659 DF = 2 p = 0.924692), or with
the intron 2 VNTR polymorphism (LRS = 0.8795 DF = 2 p = 0.6442).
When we performed a haplotype analysis, we found no association
between suicide attempt and haplotype distribution (LRS = 1.8426 DF =
4 p = 0.764681).
Conclusion: These findings suggest that this new polymorphism in 5-HTT
gene may not influence suicidal behaviour in bipolar disorder.
S-21-03
Moderating effects of 5-HTT, MAO-A and COMT polymorphisms on early life stress: Evidence from primate studies
Christina Barr
Poolesville, MD, USA
Introduction: A loss-of-function polymorphism in the human serotonin
transporter gene promoter (5-HTTLPR) increases risk for developing
depression in the face of adversity. In macaques, there exists an orthologous polymorphism (rh5-HTTLPR), which has also been shown to diminish
transcriptional efficiency.
Method: Rhesus macaques (M. mulatta) were raised either by their
mothers (MR) or in peer- only groups (PR), a model for early adversity.
Animals were genotyped for the rh5-HTTLPR polymorphism, and the
effects of peer rearing and rh5-HTTLPR on responsivity to stress was
assessed using a social separation paradigm.
Results: The rh5-HTTLPR short (s) allele interacts with exposures to adversity to influence behavioral and endocrine stress responding in infancy.
Infants reared with their mothers that were carriers of the s allele were
more likely to sensitize to repeated mother-infant separation, where as
those homozygous for the l allele were able to adapt. When we examined
interactive effects with early rearing history, we found that PR infants that
were carriers of the s allele were more likely to become agitated during
stress exposure and were also more likely to develop behavioral pathology during social separation. This was particularly evident among female
infants.
Conclusion: These studies demonstrate an association of the rh-HTTLPR
s allele with reactivity to stress in macaques exposed to early stress in the
forms of peer rearing or repeated mother-infant separation. The identification of functionally-equivalent 5HTTLPR variants that are observed at
relatively high frequencies in both rhesus and humans may suggest that
these loci are maintained by balancing selection. Our studies in macaques
demonstrate that the rh5HTTLPR polymorphism influences behavioral
adaptation to stress, despite the fact that it also confers increased risk for
behavioral pathology. It may be that similar selective pressures have maintained the 5HTTLPR, and other functional 5HTT polymorphisms, in human
populations.
S-21-04
The hunt for polymorphisms: Expectations and disappointments
Johan A. Den Boer
University Medical Center, Department of Psychiatry, Groningen,
The Netherlands
M. Jabbi, I. Kema, C. Hartman, J. Ormel
Introduction: Depression is a complex disease in which several different
causes, including life events and genetic risk factors may interact in complex ways. We investigated the influence of genetic polymorphisms (catechol- O-methyltransferase polymorphism (COMT) and variants of
MonoAmino-Oxidase-A (MAO-A) genes) on endocrine and behavioural
responses to a psychological and neuroendocrine stressor.
Method: We included three groups of individuals with different degrees
of susceptibility to major depression (MD) (i.e., healthy controls, firstdegree relatives and patients suffering from MD). They underwent a psychological stressor, a simulated public speaking task (Groningen Acute
Stress Test: GAST) and a neuroendocrine stressor, the DEX/CRH challenge.
Results: Allelic variations of COMT polymorphism were found to influence
the degree of plasma epinephrine (EPI) response and subjective experience
of stress. Interactions between COMT and diagnostic groups in measures
of plasma EPI, cortisol and subjective responses to psychological stress
were also found. We found that COMT and MAOA functionally interact
on the HPA-axis response to psychological stress, whereas during the
endocrine challenge, only significant main effects of these genotypes were
observed. Interestingly we found an interaction between COMT and
MAOA with respect to the ACTH response to the GAST (see Fig.1).
Conclusion: These observations support a possible role for COMT in the
endocrine and subjective response to psychological stress and thus may
qualify as a possible candidate gene involved in the pathogenesis of MD.
In addition, our findings show that interactions between MAOA and
COMT genes may influence the degree to which subjects respond to a
psychological stressor, thus determining the vulnerability for the development of major depression. Figure 1 depicts low activity MAOA interactions with COMT allelic variations in mean (SEM) percentage change in
plasma ACTH during all stressors except SP (speech preparation). Legend:
PS= public speaking; MA= mental arithmetic; FG=rank ordering task with
Financial Gain; FL= Financial Loss.
13
ANXIETY - Symposia
S-07
New perspectives in anxiety disorders
T4 Anxiety
S-07-01
Needs and trends in the treatment of anxiety disorders
Jakov Shlik
University of Ottawa, Department of Psychiatry, Ottawa, Ontario,
Canada
Anxiety disorders (AD) are the most common psychiatric illnesses worldwide. Lifetime prevalence for any AD nears 30% with a median age of
onset at 11 years. The prevalence in a given year reaches 18% with 3050% of cases in the serious range of clinical severity and impairment.
Many patients with AD develop unremitting course of illness complicated
by psychiatric and medical morbidiy, social maladjustment and disability.
There is an increasing recognition of unmet needs in the management of
AD. Treatment directions in the field have come a long way from conceptual arguments to evidence-based consensus. Recent authoritative guidelines for the most part agree that medications and cognitive-behavioural
therapies (CBT) are equally effective first-line treatments for all categories
of AD. Among medications, the preference is given to selective serotonin
reuptake inhibitors (SSRI) and serotonin and norepinephrine reuptake
inhibitors (SNRI) with a more limited role for benzodiazepine anxiolytics.
Use of CBT should optimally follow empirically based protocols in a disorder-specific format. However, numerous challenges exist in implementing
the guidelines in clinical reality. Many patients with AD fail to improve or
can not tolerate the indicated treatments. Miscellaneous algorithms for
switching, augmentation, combining and sequencing treatments are still
more art than science. The prospects of biological and genetic markers
and novel pharmacological approaches remain elusive. On the systems
level there is a need for optimization of services across primary and specialized care to ensure appropriate resources, accessibility, continuity and
improved outcomes in the management of patients with AD.
S-07-02
Genetic and environmental risk factors for anxiety disorders
John M. Hettema
Institute for Psychiatric Genetics, Dept. of Psychiatry, Richmond, VA, USA
The anxiety disorders represent a heterogeneous group of syndromes
which are common, chronic, and possess extensive comorbidity. They are
complex genetic disorders that exhibit moderate familial aggregation and
heritability. While the findings of family studies are mixed, twin studies
suggest that anxiety disorders share genetic risk with each other, major
depression, and stable personality traits such as neuroticism. This has
important implications for strategies targeted at identifying susceptibility
genes underlying these conditions. Likewise, common patterns of environmental risk have been identified. In this presentation, we will review
these findings and their impact on recent gene finding efforts for the
anxiety disorders.
S-07-03
Neurobiology of anxiety disorders: Beyond serotonin
Eduard Maron
University of Tartu, Psychiatry, Estonia
Anxiety disorders are serious and most prevalent psychiatric diseases, the
neurochemical and neurobiological origins of which are not fully understood. In the past decade, the specific involvement of serotonin in the
pathogenesis and neurobiology of anxiety has been extensively tested in
a broad scope of investigations including experimental studies, brain
imaging, and genetics. Two direct serotoninergic interventions, including
tryptophan depletion and acute administration of serotonin precursors,
appear to be particularly relevant in challenge studies. The results of challenge studies confirm the dual role of serotonin in the modulation of various forms of pathological anxiety. The brain-imaging research has provided more evidence of neurobiological substrates in anxiety disorders.
14
The recent findings demonstrate that alterations in the brain serotonin

system may vary among different anxiety disorders and probably depend
on their clinical status. Furthermore there are increasing efforts to determine anxiety vulnerability genes in the serotonin system. Overall, the
association studies of gene polymorphisms in the serotonin system in anxiety disorders have produced results that are inconsistent, negative, or
not clearly replicable. Therefore it would be an oversimplification to consider serotonin dysfunction as the single or primary pathogenetic factor in
anxiety. However there is growing evidence suggesting that interactions
between serotonin and other systems are of particular interest for further
understanding the neurobiology of anxiety disorders.
S-07-04
Future classification of anxiety disorders
Joseph Zohar
Chaim Sheba Medical Center, Psychiatry A, Ramat Gan, Israel
Currently, although there is quite good agreement between the ICD-10
and the DSM IV in regard to diagnosis of anxiety disorders, there is a
major difference between them, which is that, according to the DSM IV,
OCD is part of the anxiety disorders, but according to the ICD-10, it is a
stand-alone disorder. This kind of different approach points out one of
the major issues in diagnosis in general and diagnosis of anxiety disorders
in particular, which is the low validity of the diagnosis. The current diagnostic system, although it has improved the reliability of the diagnosis of
different anxiety disorders, it did not take us too far in regard to improving the validity. The way to increase the validity is by finding biological
markers, including endophenotype markers that would give an external
validation of the current diagnostic system. Although we are far from
being there, at least the intention of the different committees who are
working on the DSM V is to strive to find such biological markers, and to
implement them in future diagnostic systems.
S-11
Impulsivity across the psychiatric disorders
T4 Anxiety
S-11-01
Endophenotype of impulse control disorder: From concept
to treatment
Joseph Zohar
Chaim Sheba Medical Center, Psychiatry A, Ramat Gan, Israel
Impulsivity is a symptom dimension that goes behind specific diagnosis.
In addition to the impulse control disorders listed in the DSM IV, there are
other disorders with elements of dysregulated impulsivity. Those disorders
include bipolar disorder, substance use, PTSD, trichotillomania, gambling,
some of the paraphilia, etc.In each of these disorders, the presence and
degree of impulsivity should be taken into account in the treatment plan.
In the session we will explore the different presentations of dysregulated
impulsivity, not only in different psychiatric disorders, but across the lifespan as well. However, manifestation of the trait of impulsivity changes
throughout development and therefore, the dysregulated impulsivity in
adults is different as compared to children.The vast majority of psychiatric
disorders are often accompanied by comorbid disorders or associated
symptom domains that shape their expression and the course of those
disorders. For example, the presence of affective instability in patients
with impulsivity may suggest that a trial of mood stabilizers is appropriate. Although the exact mechanism by which the comorbidity of affect
and impulse dysregulation occurs has not been identified as of yet, the
presence of more than one psychiatric disorder is the rule rather than the
exception. The presence of a comorbid condition or associated symptom
complicated both the diagnosis and treatment of impulse control disorder.In the session, we will explore the implications for diagnosis of disorders with impulsivity throughout different diagnostic schema, and examine their clinical implications along those lines. Focusing more attention
on this dimension will improve recognition of it, and encourage exploration of new treatment avenues for this important dimension.
ANXIETY - Symposia
S-11-02
Impulsive symptoms and traits in patients with different
psychiatric disorders (pathological gambling, eating disorders, atypical affective disorders and personality disorders)
and its relationship with depression
Jose Carrasco
Madrid, Spain
Introduction: The association of impulsive temperament and emotional
dysregulation has been proposed historically as the substrate for several
disorders with impulsive symptoms. These disorders, such as eating disorders, impulse control disorders, addictions and atypical affective disorders, are conceptually close to the old neurotic spectrum. However, phenomenological and neurobiological evidence suggest that they constitute
a distinct nosological cluster.
Method: Biological indexes, including platelet monoamine oxidase activity,
prolactin response to serotonin agonist, tryptophan depletion and lowdose dexamethasone suppression test were performed in patients with
pathological gambling, eating disorders, atypical depression and fybromialgia and compared with studies in borderline disorder.
Results: Impulsive disorders, eating disorders, pathological gambling and
fybromialgia/atypical depression are characterized by increased emotional
instability and affective reactivity. Neurobiological findings, as with other
impulsive syndromes, indicate low platelet MAO, decreased prolactin
response and increased cortisol suppression.
Conclusion: Several disorders with impulsive behaviors in the DSM-IV
might have emotional instability as the primary dysfunction. Borderline
personality disorder might be biologically and nosologically closer to these
syndromes than to the rest of personality disorders
References: Carrasco JL,Daz-Mars M, Pastrana JI, Molina R, Brotons L,
Lpez-Ibor MI, Lpez-Ibor JJ: Hypothalamic-pituitary-adrenal response in
borderline personality disorder without posttraumatic features. British
Journal of Psychiatry 2006, in press. Basurte E, Diaz-Marsa M, Martin O,
Carrasco JL. Childhood trauma, impulsivity and hypothalamic-pituitaryadrenal axis dysfunctions in eating disorders. Actas Esp Psiquiatr. 2004
May-Jun;32(3):149-52.
S-11-03
Impulsivity in intermittent explosive disorder and impulsive aggressive personality disorders
Larry Siever
Mount Sinai School of Medicine, Psychiatry, New York, USA
Introduction: Cluster B personality disorders are often associated with
impulsive aggressive behaviors that meet criteria for intermittent explosive
disorder - revised (IED-IR). Genetic, neurotransmitter probes studies, and
neuroimaging studies have begun to clarify the underlying neurobiology
of this impulsive aggression. Prefrontal cortical inhibitory regions such as
orbital frontal and anterior cingulate cortex play an inhibitory role in
amygdala activation in response to provocative stimuli. Serotonin facilitates this top down inhibitory control.
Method: The serotonin transporter was labeled with [11C] DASB binding
in 12 patients with IED-IR and in 12 healthy control subjects matched for
age and gender. Binding of [11C] MDL 100907 to the 5HT2A receptor
was analyzed in 27 patients with IED-IR and 24 matched healthy controls.
In an FDG PET paradigm, 33 IED-IR patients with concomitant borderline
personality disorder and 24 controls were tested during anger provocation as well as a non-provocation scan.
Results: The IED-IR patients had significantly lower 5-HTT binding with
[11C] DASB in the anterior cingulate cortex with a reduction of approximately 35% in these patients. 5HT2A receptor binding with [11C] MDL
100907 was increased in currently physically aggressive subjects with correlations between aggression and OFC 5HT2A receptor binding. In the
FDG PET study, after provocation increased anterior cingulate cortical
metabolic activity while it decreased this activity in the patients and metabolic activity by FDG PET in the anterior cingulate cortex correlated positively with aggressive responding.
Conclusion: Anterior cingulate cortex is a critical region in inhibiting the
expression of aggression and is less active in impulsive aggressive patients
compared to controls. Reduced transporter activity possibly reflecting
reduced serotonergic intervention as well as increased 5HT2A receptor
binding appears to contribute to the underactivity of anterior cingulate

gyrus supporting the possibility of pharmacologic intervention of the
serotonergic system for treatment of impulsive aggression.
S-11-04
Affect regulation and impulsivity in borderline personality
disorder
Sabine Herpertz
Rostock University, Psychiatry and Psychotherapy, Germany
Introduction: Impulsivity is one of the most prominent characteristics of
borderline personality disorder (BPD). Three domains of psychopathology
target the problem of impulsivity in BPD: Impulsive modes of behavior,
cognitive disinhibition, and dysregulated emotions.
Methods: Facets of cognitive functioning and emotional processing have
been investigated in different samples of female BPD inpatients using
neuropsychological tasks and emotion challenge tasks. In addition to
behavioral data functional activity to emotionally charged stimuli were
assessed in a series of experiments in female BPD patients.
Results: Data suggest that cognitive disinhibition exclusively occurs in the
context of processing emotional but not neutral stimuli. A bias towards
anger was found for ambiguous facial stimuli indicating distorsions in
social perception. Regarding functional activity data suggest that amygdalar hyperreagibility underlies high arousal processing of emotionally
relevant stimuli that is not sufficiently suppressed by prefrontal top-down
control. In addition, BPD patients exhibit a general tendency towards a
self-referential mode of information processing indicated by an enhanced
involvement of the cerebral memory retrieval network.
Conclusion: The findings provide a neurobiological basis for the notion
that impulsivity is closely related to dysregulated emotions in BPD.
Emotional hyperarousal together with distorsions in social perception may
increase the risk of reactive (auto)aggression in BPD.
References: Schnell K, Dietrich T, Schnitker R, Daumann K, Herpertz SC.
Processing of autobiographic memory retrieval cues in borderline personality disorder. J Affective Disorders, in pressDomes G, Winter B, Schnell
K, Vohs K, Fast K, Herpertz SC (2006) Inhibitory functioning in borderline
personality disorder and the influence of emotions. Psychological
Medicine, 36:1163-1172Herpertz SC, Dietrich TM, Wenning B, Erberich
SG, Krings T, Thron A, Sass H (2001) Evidence of abnormal amygdala
functioning in borderline personality disorder: a functional MRI study.
Biological Psychiatry 50(4):292-298
S-44
PTSD and depressive spectrum disorders
T4 Anxiety
S-44-01
Magroob
India
S-44-02
Neurobiology of PTSD
E. Mohandas
India
Introduction: Although the conceptual framework of Posttraumatic
stress disorder is a matter of debate, there are attempts to delineate neuroanatomical correlates of symptom clusters of PTSD. Neuroimaging provides a reasonable model of neurocircuitry of PTSD. This paper critically
evaluates the available evidence on functional neuroanatomy and neurochemistry of PTSD.
Method: The existing data on neurobiological basis of PTSD was evaluated
using various search engines (Pubmed, Ebsco, Science direct, Ovid)
Results: The neural substrates and circuitry of PTSD are formulated. A
critical appraisal of the neurochemical alterations is attempted.
Conclusion: The available evidence suggests that the neurochemical
changes may vary depending on the type,magnitude,and duration of the
stress.The cognitive dysfunction may be due to working memory dysfunction rather than hippocampal changes.
15
ANXIETY - Symposia
References: Nemeroff CB, Bremner JD, Foa EB, Mayberg HS, North CS,
Stein MB. (2005) Posttraumatic stress disorder: a state-of-the-science
review. J Psychiatr Res., 40(1):1-21. Rauch SL, Shin LM, Phelps EA. (2006)
Neurocircuitry models of posttraumatic stress disorder and extinction:
human neuroimaging researchpast, present, and future. Biol Psychiatry,
60(4):376-82. Shin LM, Rauch SL, Pitman RK. (2006) Amygdala, medial
prefrontal cortex, and hippocampal function in PTSD. Ann N Y Acad Sci.,
1071:67-79. Bremner JD. (2006) The relationship between cognitive and
brain changes in posttraumatic stress disorder.Ann N Y Acad Science,
1071:80-6.
S-44-03
Treatment approaches to PTSD
Sunil Mittal
India
Manu Mittal
Introduction: The presentation reviews current treatments and the
Indian experience in quantifying, diagnosing and treating PTSD and the
lessons from work with those affected by terrorism, and natural disasters
like cyclones, earthquakes and Tsunami.
Conclusion: PTSD is not an inevitable consequence of trauma but represents one of the evolving responses to trauma. Stress reactions may serve
the primordial function of adaptation and survival. Earlier lower reported
incidence of PTSD was possibly due to reporting bias and its presentation
more as somatic symptoms. Progressive relaxation of the stressor criteria
today reflects changes in societal values. Since the psychopathology of
trauma is dynamic and culture affects the expression of distress and
painful memories, PTSD has also been viewed as a contemporary culturebound syndrome. Even as the broadening definition of trauma confounds the issue of greater understanding of the psychobiology of PTSD,
yet our knowledge of the neurobiology of post-traumatic symptoms has
increased. The brain is a master-controller of stress reactions as well as the
prime target of their effects. Exposure to manageable stress helps the
brain adapt for greater endurance, working and immunity; extreme stress
damages the brain inhibiting memory functions; and catastrophic experiences may change the structure and functioning of the brain. As in
depression, impairment of structural plasticity and cellular resilience is
implicated in PTSD. Very high levels of catecholamines and endorphins
seen in PTSD may interfere with storage of explicit (declarative) memory
causing trauma memories being stored as implicit (non-declarative) memory: as emotions and senses. This may lead to intrusive recollections, malassessment of further danger signals or non-threatening events and survivors reacting with panic attacks, flashbacks and overwhelming emotions probably due to situationally accessible (vs. verbally accessible)
memories. Pharmacological treatments for PTSD include SSRIs, other antidepressants, bezodiazepines, mood stabilizers, antipsychotics and drugs
like clonidine. Little work exists on early pharmacological interventions to
prevent PTSD. Non pharmacological treatments include cognitive and
other behavioural therapies, EMDR, debriefing, ventilation, relaxation,
spiritual and supportive therapies, self-help groups, mass grieving and
bibliotherapy.
S-44-04
S. Nambi
India
S-47
PTSD - state of the science
T4 Anxiety
S-47-01
Insights from animal models in PTSD
Masashi Nibuya
Tokorozawa, Japan
Introduction: To better understand the effects of environmental stress
on psychiatric disorders, many stress studies have been performed using
16
experimental animals. Compared to apparent difficulties in making animal models of endogeneous psychoses including schizophrenia and affective disorders, the PTSD animal models are expected to be established in
an earlier time point in the future. For traumatic stressogenic stimuli in
PTSD animal models, various procedures have been adopted including
predator scent paradigm, restraint stress, electric tail shock, and underwater trauma. In order to obtain life threatening-level stress and examine
behavioral effects of rats under the same traumatic environment, we have
adopted multiple inescapable electric foot-shocks treatment and
observed behaviors in the shuttle box at the 14-day later (Sawamura et
al, 2004). We have recently demonstrated that the inescapable footshock stress paradigm promptly induces endoplasmic stress pathway
which can ultimately trigger neuronal apoptotic cell death in the rat brain
(Toda et al, 2006). We consider ER stress mechanism together with already
reported brain glucocorticoid dysfunctioning and reduced neurogenesis
in the hippocampal brain region possibly via reduced neurotrophin signaling (Nibuya et al, 1995) have effects on brain volume loss in PTSD and
depression.
Results: The splicing of 26 nucleotides in the coding region of the X-box
binding protein-1 (XBP-1) transcript to generate a mature active transcription factor is a part of the unfolded protein response to intracellular endoplasmic reticulum stress. In this study, we demonstrated that XBP-1 splicing is promptly induced in the rat brain including the hippocampus by
both inescapable electric foot shock (IS) and pharmacologically manipulated activation of 5-hydroxytryptamine release in a dose-dependent
manner. By administering ketanserin, a 5-hydroxytryptamine 2A antagonist, however, we could only partially block the increased splicing by IS
and observed that the splicing was not influenced by lithium carbonate
pretreatment.
Conclusion: Although it is still unclear whether the enhanced unfolded
protein response functions neuroprotectively by modulating the rate of
general translation and increasing chaperone proteins or whether it eventually induces cellular damage by triggering apoptosis, the present results
indicate the possible existence of a new adaptive intracellular signaling
pathway in the brain that responds to environmentally challenged behavioral stress loading.
References: On the meeting we additionaly present expressional alteration of GPR56 protein involved in neuronal migration and differentiation by behavioral stress loading.
S-47-02
Injury increases the risk for PTSD, potential neurobiological
and psychological mediators
Ehud Klein
Rambam Medical Center, Department of Psychiatry, Haifa, Israel
Danny Koren
Given the frequency with which common traumatic events involve both
physical and emotional injuries, a crucial question arises: How do these
two interact? How does injury affect an individuals chances of developing
PTSD? Traditional views, tended to regard bodily injury as a protective factor against the development of posttraumatic stress disorder suggesting
that the healing and rehabilitation process shifts the individuals attention
away from the negative emotional consequences of the trauma.In contrast, more recent literature on this topic suggests that injury during a
traumatic event might in fact increase the probability of developing
PTSD.In this talk findings from a recent study will be presented, showing
an eight-fold higher risk for develepment of PTSD in soldiers who were
injured during military traumatic events as compared to their comerades
who participated in the same events, but were not injured.These results
indicate that physical injury, over and above exposure to the traumatic
event itself, is a risk factor for PTSD.The discussion will relate to contemporary findings regarding the neurobiological and psychological mechanisms by which injury may augment or independently contribute to the
development of PTSD.
S-47-03
Rachel Yehuda
USA
CHILDHOOD & ADOLESCENT DISORDERS - Symposia
S-02
The challenge of suicide in adolescents
T5 Childhood & Adolescent Disorders
S-02-01
Epidemiology of suicide
Edith Serfaty
Buenos Aires, Argentina
Introduction: Young people in Argentina are exposed to death by suicide.
Objective of this research was to study the suicide death between young
people during 1991 to 2000. The Epidemiological Research Center of the
Buenos Aires Academy of Medicine did the study with all the countrys
death dates certified by the Ministry of Key words: suicide-adolescence.
Method: Material and Methods: Population studied; all the death by suicide of people between 10 to 24 years old, of Argentina, since 1991 to
2000 in the country and each area. Statistical analysis: Mortality rates
were calculated on yearly per province and per country.
Results: Suicide rates for this age both sexes was 6.1 per 100.000 inhabitants. It was 9% of the total adolescents death. The rate increased
between 1991 and 2000 from 1.3 to 6.1.
Conclusion: HealthDiscussion: It was detected the following risk factors.
Late adolescence, male sex. It was more elevated on males. Results showed
that suicide was a significant problem for Public Health and the community.
References: Yunes Jo, Zubarew T. Mortalidad por causas violentas en
adolescentes y jvenes. Un desafo para la regin de las Amricas. Rev.
Bras. Epidemiol 1999. 1 (3): 102-71. Dehne KL, Riedner G. Adolescence,
a dynamic concept. Reprod. Health Matters 2001, 9 (17), 11-5. Instituto
Nacional de Estadsticas y Censos (INDEC). Proyeccin de poblacin por
edad y sexo. Total del pas. Anlisis demogrfico N 7, INDEC 1995.
S-02-02
Biology of suicide
S-02-04
Risk of suicide and antidepressants
Leonardo Tondo
Harvard Medical School, McLean Hospital, Belmont, USA
Suicide is a particularly urgent challenge in children and adolescents in
whom depression is less recognized and substance abuse is more common(1) than in adults. The question of whether modern antidepressant
treatments can affect mortality rates is only beginning to be addressed.
Most studies of treatment effects on suicide have been naturalistic or
have encountered suicidal behavior as an unintended outcome in controlled treatment trials. Moreover, ethical issues can make study designs
difficult when death is a possible outcome. Ecological studies based on
the association between use of antidepressants and risk of suicide in
defined populations treated with antidepressants yielded inconsistent
results. Also clinical studies on the same subject did not seem to provide
consistent results. It is interesting to note that introduction of safer antidepressants with very low lethality on overdose since the 1980s has led
to marked increases in antidepressant usage, but not to a measurable
reduction of suicide rates. However, studies including only children and
adolescents are relatively few. The only ecological study on adolescents
aged 10-17 years treated with antidepressants did not show significant
modification of the suicide rates(2). A very recent matched case-control
study(3), reinforced a significant association between the use of antidepressants and the increase of completed and attempted suicides in
depressed children and adolescents. Studies on this topic have become
more important after an association between increased suicidality in children treated with antidepressants emerged as a result from meta-analyses of data reported to regulatory agencies in the UK and US.
References: 1. Tondo L, Baldessarini RJ, Hennen J, Minnai GP, Salis P,
Scamonatti L, Masia M, Ghiani C, Mannu P: Suicide attempts in major
affective disorder patients with comorbid substance use disorders. J Clin
Psychiatry 1999; 60: 63-9. 2. Sndergrd L, Kvist K, Andersen PK, Kessing
LV. Do antidepressants prevent suicide? Int Clin Psychopharmacol 2006;
21: 211-218. 3. Olfson M, Marcus S, Shaffer D. Antidepressant Drug
Therapy and Suicide in Severely Depressed Children and Adults: A CaseControl Study. Arch Gen Psychiatry 2006; 63: 865-872.
Jose-Luis Ayuso Gutierrez

Madrid, Spain
Suicide behavior is probably best understood in the context of a model
of stress-diathesis. Substantial evidence suggest that low brain serotonergic function and genetic factors contribute to reduce the suicide threshold . On the other hand, other risk factors contribute to the development
of suicide behavior like depression, mania, psychosis, substance abuse
and stressful life events. Investigations of biological substrates of suicide
risk were initiated almost 30 years ago. These early studies indicated an
association of suicidal behavior and low 5-HIAA in the CSF, that was correlated with the lethality of the attempt. Later, the elucidation of the neurotransmitter receptors disordered in the pathophysiology of suicide has
been the subject of intense post-mortem studies. The majority of the
studies have measured binding of the SERT in tissue preparations from
various brain regions, particularly the frontal cortex. Most studies show a
decreased SERT binding in PFC of suicide victims indicating low serotonin
function. More recently, increased binding of 5-HT1A in PCF of suicide victims has been found indicating a compensatory response to low serotonin.
Several research groups have demonstrated genetic contributions to suicidal behavior through both family studies and molecular genetics. Other
investigators have sought to link suicide behavior to genetic variations of
the SERT, although these efforts have produced inconsistent results.
S-02-03
Eduardo Correa
Universidad de Chile, Clinica Psiquiatrica Univ., Oviedo, Chile
17
NEURODEGENERATIVE DISORDERS - Symposia
S-17
Vulnerability and resilience factors in depression
and dementia
T6 Neurodegenerative Disorders
S-17-01
Oxidative stress and clinical implications in dementia
Anne Eckert
Psych. Univ. Clinics Basel, Neurobiology Laboratory, Switzerland
Introduction: Oxidative stress caused by reactive oxygen species plays a
decisive role in the pathogenesis of neurodegenerative disorders such as
Alzheimer's disease (AD). Mitochondria are the primary source and main
target of reactive oxygen species (ROS) within cells.
Methods: Different methods were used to identify oxidative stress and
mitochondria malfunction in brains from transgenic mice or cell culture
models.
Results: Early defects in glucose utilization in the brains of AD patients
suggest possible abnormalities in mitochondrial function in AD. Several
studies have indicated that amyloid-beta protein (A) may be directly
toxic to isolated mitochondria. Interestingly, the activities of those enzymes, which are reduced in the brains of AD patients, such as COX, alphaketoglutarate dehydrogenase and pyruvate dehydrogenase were inhibited by A. Recently, it has been demonstrated that A can be formed
intracellularly in neurons. A large amount of evidence suggests that mitochondria could intervene in the mechanism by which intraneuronal A
triggers neuronal dysfunction and degeneration. In our own studies, we
could clearly demonstrate that A causes oxidative stress and mitochondrial malfunction in a cell culture model as well as in transgenic mice (Keil
et al., 2004). In addition, recent data of our group demonstrate a link between tau pathology and mitochondrial malfunction. Using transgenic
mice, we could demonstrate mitochondrial dysfunction by proteomic and
functional analyses in these mice (David et al., 2005). Thus, we can speculate that tau and A accumulation probably act in synergy on oxidative
stress and mitochondrial dysfunction. Of note, Ginkgo biloba extract EGb
761 and piractem at therapeutically relevant in vitro and in vivo concentrations are able to improve mitochondrial dysfunction associated with
oxidative stress and/or aging (Eckert et al., 2005; Keil et al., 2006).
Conclusion: In summary, protection against mitochondrial dysfunction,
improved ATP production, and prevention of apoptotic signals may be
important features of antidementive drugs. Since mitochondrial failure
and reduced energy metabolism seem to be very early events during the
course of AD, the stabilization of mitochondrial function represents an
emerging preclinical concept of age-related memory disorders and
dementia.
References: David et al., J. Biol. Chem. 280:23802-23814, 2005; Eckert
et al., Ann. NY Acad. Sci. 1056:474-485, 2005; Hauptmann et al., Exp.
Gerontol. 41:668-673, 2006; Keil et al., J. Biol. Chem. 279:50310-50320,
2004; Keil et al., Br. J. Pharmacol. 147:199-208, 2006
S-17-02
Natural neuroprotective substances in neurodegeneration
Egemen Savaskan
Psychiatric Univ. Hospital, Dept. of Psychiatry Research, Zrich,
Switzerland
Introduction: A complex neuropathology underlies neurodegenerative
disorders such as Alzheimers disease (AD). One of the hallmarks of AD is
widespread neuronal and synaptic losses. The two major neuropathological findings in the AD brain are the presence of neuritic plaques containing -amyloid (A) and neurofibrillary tangles. That oxidative stress may
be a culprit in neuronal loss in AD has been emphasized in recent years
and the evidence is becoming progressively stronger that radicals are
involved in the neuronal pathogenesis of the disease. The free radicals
that have been incriminated as causing neuronal loss are believed to be
generated by A.
Methods: Today, it is well established that some human hormones have
obvious anti-oxidative capacity.
18
Results: These hormones play an important role in the functioning of the

central and peripheral nervous system, have neuroprotective effects, and
their levels markedly decrease with age and in AD. They may provide a
natural source of neuroprotection in neurodegenerative disorders.
Conclusion: Therefore, the aim of the present work was to uncover the
neuropathology altering hormonal effects in AD and to establish the neuroprotective effects of these substances. Two of them, melatonin and
estrogen, respectively, will be discussed in detail.
S-17-03
Neuroendocrine and sleep regulation as predictors of illness course and therapy in depression
Martin Hatzinger
University Hospital Basel, Psychiatric Outpatient Clinic, Switzerland
U. Hemmeter, S. Brand, M. Ising, Edith Holsboer-Trachsler
Introduction: Introduction: In acute depression characteristic changes in
EEG sleep measures are well documented findings. However, the course
and the predictive value of these alterations for treatment outcome as
well as for long-term course of depression still warrants clarification.
Therefore, we examined whether (1) the previous clinical course of
depression, (2) treat-ment response during a standard antidepressant
therapy, and (3) the long-term outcome in follow-up are associated with
abnormal EEG sleep parameters. Since the hypothalamic-pituitaryadrenocortical (HPA) system seems to play a crucial role in treatment outcome and course of depression, we evaluated HPA system function as
well.
Method: Methods: 15 patients (4 men, 11 women; age 43-59) with
depression were enrolled in the study. HPA system assessment using the
combined DEX/CRH test and sleep EEG studies were conducted at baseline, after a 6 week antidepressant treatment period (trimipramine), and
at follow-up i.e. after 2 to 10 years after the index episode.
Results: Results: 1. The previous clinical course as reflected by the number of episodes until base-line correlated significantly with EEG sleep
measures i.e. sleep continuity values, slow wave sleep (SWS) and REM
latency. 2. During treatment sleep continuity values improved and the correlation with the previous long-term course disappeared. However, the
correlation with SWS persisted. The only sleep EEG marker at baseline
predictive for treatment response was REM latency. 3. In the prospective
long-term outcome SWS and REM density variables were related to the
occurrence of recurrences in follow-up. These identified sleep EEG markers correlated closely with HPA system regulation.
Conclusion: Conclusions: The previous and the prospective long-term
course of depression are related to sleep EEG variables during the acute
depressed state at the beginning and the end of treatment. Among the
different values SWS and REM density measures seem to reflect predictive
markers for the long-term course of depression. These markers are associated with HPA system regulation.
S-17-04
Neuroendocrine molecular regulation of anxiety, stress and
depression
Eduardo Arzt
University of Buenos Aires, Argentina
Introduction: Corticotrophin releasing hormone (CRH) is the key mediator of the central nervous system response needed to adapt to stressful
conditions. If adaptation fails hypersecretion of CRH continues and produces via stimulation of CRH type 1 receptors (CRHR1) symptoms pertaining cognition, appetite, sleep, anxiety and stress hormone secretion
underscoring that this pathway is causally involved in affective disorders.
New basic studies indicate that the final outcome of CRH/CRH1 signaling
depends on the context of specific cells and ligands, cross-talk of signaling pathways and the effector actions of the pathways once they are activated. This specificity bears consequences at the CNS level where CRH
activates through the same receptor (CRHR1) different signaling pathways depending on neuroanatomical context. These findings open up the
opportunity for a more focused pharmacological intervention.
S-43
Prevalence and impact of dementia in Latin
America - 10/66 dementia research group
S-43-01
Prevalence of dementia in Latin America - ethnic and racial
differences
Juan Llibre Rodriguez
Univ. Medica de la Habana, Medicina Finaly Albarran, Cubanacan Playa,
Ciudad Habana, Cuba
M. Prince, Cleusa Ferris
Introduction: Demographic ageing is proceeding especially rapidly in
Latin America. Estimates based on the literature suggested 1.8 million
people with dementia now increasing to 4.1 million by 2020 and 9.1 million by 2040, that is the number of people with dementia will be very
similar in Latin American as North America.
Method: After pilot studies the 10/66 Dementia Research group has
been finished prevalence studies in six developing countries in Latin
American: Argentina, Cuba, Dominican Republic, Mexico, Peru, and
Venezuela. Each of these studies uses the same design (a comprehensive
one phase survey of all residents aged 65 and over, with a minimum sample size of 2 000 in each of the six countries, for a total sample of
12 000 individual from rural and/ or urban catchment areas. All participants are interviewed with a sociodemographic, risk factors and health
behaviours questionnaire, a cognitive test battery and a structured clinical
interview. A physical and neurological examination follows, with anthropometry and phlebotomy.
Results: There are large differences between centres in diet, levels of
activity and cardiovascular risk factor profiles. The Peruvian sample seems
to have strikingly low levels of cardiovascular risk, with a low prevalence
of smoking and very low blood pressure levels. Hypertension and other
vascular factors are most prevalent in Cuba and Venezuela. The prevalence of probable dementia according to screening measures, and DSM
IV criteria increase with age and decline with education. The 6.4% prevalence in Cuba is significantly higher than in all other centres, follow by
Venezuela and Dominic Republic. The prevalence of DSM IV dementia
and also the association between APOE4 and DSM IV dementia were
more higher in white people that in people with African ancestry.
Conclusion: The prevalence of dementia is high in Latinamerican countries as in developed world. Risk factors for vascular disease such as high
fat diets, cigarette smoking, diabetes, hypertension and sedentary
lifestyles are common.
S-43-02
Mariella Guerra
Lima, Peru
S-43-03
10/66 Dementia diagnostic validity
Ana Luisa Sosa Ortiz
Instituto Nacional, Mexico City, Mexico
Introduction: The 10/66 Dementia Research Group was integrated in
1988 based in the following facts: 1. Two-thirds of people with dementia
live in developing countries. 2. In the next 30 years there will be a large
increase in dementia cases in DCs. 3. Less than 10% of population-based
research is targeted on DCs. Then, it is necessary to generate: a. Good
quality research b. Awareness c. Shape policies and d. Service development The first goal of the 10/66 Research Group is: To develop and test
a culturally and educationally unbiased diagnostic process for dementia.
Method: In order to do a cross-cultural validation study, the 10/66 R.G.
did a pilot study in which 25 international centers participated, getting a
total sample of 2885 subjects aged 60 years and older, from: India, China
and South East Asia, Latin America, the Caribbean and Africa. In this pilot
study the interviewers, blind to the diagnosis (dementia, depression, control high and low education), administrated: a. The Geriatric Mental State
(GMS). b. The Community Screening for Dementia (CSID). c. Ten word
list-learning task of the Consortium to Establish a Registry of Alzheimers

Disease (CERAD).
Results: In this pilot study, each one of the three instruments applied
independently predicted the dementia diagnosis. An algorithm with all
the instruments gave better prediction than each one individually; with
this algorithm a sensibility of 94% and a specificity of 85%, 97% and
94% in cases of: depression, high education and low education groups,
respectively, were obtained.
Conclusion: Based on these results, we conclude that the 10/66 dementia algorithm is a good option for culturally and educationally sensitive
dementia diagnosis for clinical and population-based research. After this
pilot study, the 10/66 R.G. started with population-based studies in seven
centers, getting a total sample of around 17,000 subjects evaluated with
the aim of estimate prevalence, describe impact and seek to identify
genetic and environmental risk factors in the participating settings (India,
China, Latin America and the Caribbean). This huge sample will let us
explore new and interesting validation methods.
References: -Prince M. et al. 2003. Dementia diagnosis in developing
countries: A cross cultural validation study. Lancet 361: 909-917. -The
10/66 Dementia Research Group. 2000. Methodological issues in population-based research into dementia in developing countries. A position
paper from the 10/66 dementia research group. Int J Geriatr Psychiatry
15: 21-30
S-43-04
People with dementia in Latin America - care
arrangements and caregivers strain
Aquiles Salas
Univ. Central Venezuela, Caracas, Venezuela
Introduction: Demographic ageing is proceeding especially rapidly in
Latin America. Those aged 65 years and over will increase from 33.3 million (6% of the total population) in 2005 to 56.3 million (8.5%) in 2020
and 110.2 million (14.7%) in 2040. The literature suggested 1.8 million
people with dementia in 2001 increasing to4.1 million by 2020 and 9.1
million by 2040. Arguably, health and social finance systems are not wellplaced to meet the needs of the growing numbers of frail and dependent
elderly. Across Latin America, fewer than 30% of older people receive old
age pensions (Help Age International). Health systems in Latin America
are generally Mixed National Health Systems in which public sector institutions play a relatively minor role, less than one-third are covered by
mandatory social health-insurance systems and private out-of-pocket
expenditure on health services is relatively large.
Method: Aknock door census allows to recruit 2020 subjects and theirs
caregiver in a low income population at the south west of
Caracas.Trained interviewers applied a set of mental health questionnaires, care arrangement and household information.
Results: Preliminary results shows that 7.5% of the population studied
has any type of dementia, 4.5% has MCI and 13% depression; the public institutions play a small role attending the elderly, lacking specialized
centers for demented. The care is given mainly for families caregiver
without training and support. We found that 80 % used private medical
services and 15% used public services; 20% had paid caregiver and 710% caregiver stopped or cut back work for care and 48% showed common mental disorders due to burden of care.
Conclusion: Dementia is a medical and social problem in our countries;
we may have more than 100000 families living with a person with
dementia. They have to cope with poor support and knowledge. There
are very few or none institution at the community or regional level.
References: Salas A, Mosca W, Gonzalez J La salud y el Bienestar de
los Adultos Mayores en : Salud y Equidad: Una Mirada desde las Ciencias
Sociales, Editora Fiocruz, Rio de Janeiro, Brasil, Octubre 2000. Prince M,
et al. 2003.Dementia diagnosis in developing countries: a cross cultural
validation study. Lancet 2003; 361: 909-917 The 10/66 Dementia
Research Group. 2004. Care arrangements for people with dementia in
developing countries. Int J Geriatr Psychiatry 19: 170-177.
19
S-43-05
People with dementia in Latin America - costs
Raul Arizaga
10/666 DRG, Buenos Aires, Argentina
Introduction: The demographic structure of developing countries (with
only a few exceptions) shows a population aging process that is actually
more striking than in the developed world, that has suffered the acute
phase of this graying phenomenon some decades earlier. Dementia is
considered the fourth cause of disability adjusted life years in the developing world for both sexes. The costs of dementia to society is the value
of all goods and services that are given up in order to prevent, diagnose,
treat and otherwise cope with dementia. Economic costs of AD are significant for health systems. Individuals, families and carers are affected
both in the economic aspect and in the Quality of Life (QOL). Costs are
divided in direct (money used in an explicit way in hospital, medical services, drugs, social services) and indirect (money used in an implicit way
as loss of income by the patient and loss or reduction for family members
or carers). The aim of this presentation is to analyze total, direct and indirect costs of AD and its variations in relation to disease severity and
whether patients are institutionalized or not.
Method: Eighty community dwelling patients, twenty institutionalized
AD patients and their respective primary caregivers, and twenty-five
healthy elderly subjects, participated in this study. The cognitive and neuropsychiatric impairments and severity of dementia were assessed with
MiniMental State Examination, Neuropsychiatric Inventory and Clinical
Dementia Rating respectively. One structured interview about health and
no health care resources used up during the last 3 months were administered to family caregivers. The time devoted by carers to look after the
patients and the caregiver burden (Zarits Burden Interview) was recorded.
A healthy elderly control sample was used to address the cost specifically
attributable to the disease.
Results: The annual direct cost of the disease increased with cognitive
deterioration from 3421$US in mild to 8256$US in severe, and with institutionalization (3189$US outpatient vs. 11270$US institutionalized).
Family paid mostly for direct costs.
Conclusion: With projected increase in the number of persons at risk for
developing AD in emerging countries, economic familial cost of the
disease will be significant. Dementia costs should be a matter of analysis
when health policies are being designed in developing countries.
20
PSYCHOTIC DISORDERS - Symposia
S-01
Pathogenesis of schizophrenia
T7 Psychotic Disorders
S-01-01
Disc1-interacting molecules and pathogenesis of schizophrenia: Candidate gene approach
Norio Ozaki
Nagoya University, Psychiatry, Japan
M. Ikeda, S. Taya, K. Kaibuchi, N. Iwata
Introduction: Numerous linkage and case-control association analyses
have been performed to clarify the pathophysiology of schizophrenia,
because 80% of the estimated heritability suggested that genetic factors
contribute for the development of this disorder. One of the promising
candidate genes, Disrupted-In-Schizophreina-1 (DISC1), was found in a
Scottish family with translocation of chromosome (1:11)(q42.1:q14.3)
and a high frequency of schizophrenia and mood disorders. Although the
function of DISC1 has not been fully elucidated yet, this molecule has an
important role in neurodevelopment that is hypothesized to be involved
in pathophysiology of schizophrenia. Among the DISC1-interacting molecules, 14-3-3 epsilon gene (YWHAE: located on 17p13.3) is a plausible
candidate gene for schizophrenia, because 14-3-3 epsilon is necessary for
the normal localization of NUDEL/LIS1 (also known as DISC1 interacting
molecules) and for the maintenance of NUDEL posphorylation status, participating axon elongation.
Methods: We investigate the genetic association between YWHAE and
schizophrenia in a Japanese population using two independent sets of
samples in a first-set screening analysis (SCZ=288, controls=288) and
second-set confirmation analysis (SCZ=1042, controls=1147). Since a
possible predisposing SNP in promoter region was found in this analysis,
we also carried out the functional assays to investigate the influence of
this SNP on the expression level of YWHAE through dual luciferase assay,
real-time RT PCR, and Western blotting analyses(peripheral blood samples
from controls).
Results: One SNP in 5 flanking region was significantly more frequent in
controls in first-set scan, and confirmed this significance in second-set
analysis. Further functional assays of this SNP including luciferase assay,
real time RT PCR and Western blotting also confirmed higher expression
level of YWHAE by this mutant allele of this SNP.
Conclusion: Our results indicate that this promoter SNP may reduce the
risk for SCZ by increasing 14-3-3 epsilon protein. The results of association study between clinical response of risperidone and YWHAE and between MRI-based brain morphometry and YWHAE will be also discussed
in the presentation.
S-01-02
How could the NRG-1 gene impart risk to developing
schizophrenia?
Cyndi Shannon Weickert
UNSW Dept. of Psychiatry, Prince of Wales Med. Research, Ransdwick,
NSW, Australia
Introduction: NRG1 is a replicated susceptibility gene for schizophrenia with good neurobiological plausibility (Harrison and Law 2006).
Furthermore, recent evidence has suggested that the gene encoding the
high affinity tyrosine kinase containing NRG1 receptor, ErbB4 is also susceptibility gene. However, the biological mechanism by which these
genes bring about schizophrenia is largely unknown.
Method: We used postmortem brains of patients with schizophrenia to
evaluate the mRNA and protein level of NRG1 and ErbB4 in the frontal
cortex. Furthermore, we attempted to link genomic changes with
changes in mRNA. We examined NRG1 and ErbB4 splice variant gene
expression in schizophrenia using qPCR and investigated whether expression levels are associated with previously reported genomic risk variants in
a large cohort of human brains. In order to test if any the changes in
mRNA extended to changes in protein and are diagnostically specific, we
compared relative amounts of cytoplasmic and nuclear NRGI and ErbB4
isoforms in prefrontal cortices of normal, bipolar, depressed and schizophrenic subjects. These quantities were analyzed by immunoblotting
homogenized cortical proteins with NRGI and ErbB4 antibodies that react
with the c-terminal regions.
Results: In the frontal cortex, we found elevations in NRG1 type I
(Hashimoto et al. 2004) and for JMa and CYT-1 ErbB4 splice variant
mRNA, replicating an earlier ErbB4 study (Silberberg et al., 2006). A main
effect of ErbB4 genotype on the ErbB4 JM-a mRNA levels was found. We
also found that certain SNPs and a core at-risk haplotype surrounding
exon 3 are strongly associated with elevated expression of the CYT-1
ErbB4 variant (Law et al. 2006). In terms of protein, cortical cytoplasmic
and nuclear full-length ErbB4 levels were approximately 20-30% greater
in schizophrenic patients than in normal (p<0.02), in bipolar (p=0.05) and
in depressed (p<0.02) individuals. NRG1 levels were also elevated and
correlated with ErbB4 levels.
Conclusion: These findings suggest that gene variants associated with
NRG1 and ErbB4 may work impart risk by changing splice variant specific
mRNA levels. Our data suggests that these changes in mRNA translate to
the protein level and are specific to schizophrenia as compared to other
mental illnesses. Thus, NRG1/ErbB4 signaling pathway may be an important genetic network involved in the pathogenesis of this disease. We
suggest that elevated prefrontal cortical ErbB4 signaling found in schizophrneia by earlier studies (Hahn et al., 2006) may be the consequence of
increased NRG1 and ErbB4 levels.
S-01-03
Dysbindin and pathogenesis of schizophrenia
Ryota Hashimoto
Suita, Japan
Introduction: Genetic variation in dysbindin (DTNBP1: dystrobrevin binding protein 1) has recently been shown to be associated with schizophrenia. The dysbindin gene is located at chromosome 6p22.3, one of the
most promising susceptibility loci in schizophrenia linkage studies.
Method: We performed association study in a Japanese sample of 670
patients with schizophrenia and 588 controls. We examined a possible
association between genetic variants in the dysbindin gene and memory
and IQ measured by a full version of the Wechsler Adult Intelligence
Scale-Revised (WAIS-R) and the he Wechsler Memory Scale-Revised
(WMS-R) in 165 healthy volunteers and 72 patients with schizophrenia.
Primary cortical neuronal culture was prepared from postnatal 2- or 3day-old rat.
Results: We attempted to replicate this association in a Japanese sample
of 670 patients with schizophrenia and 588 controls. We found a nominally significant association with schizophrenia for four single nucleotide
polymorphisms and stronger evidence for association in a multi-marker
haplotype analysis (p=0.00028). We further examined a possible association between genetic variations of dysbindin and human cognitive function.
Genetic variants had been associated with some category of IQ score and
memory function. We then explored functions of dysbindin protein in primary cortical neuronal culture. Overexpression of dysbindin induced the
expression of two pre-synaptic proteins, SNAP25 and synapsin I, and
increased extracellular basal glutamate levels and release of glutamate
evoked by high potassium. Conversely, knockdown of endogenous dysbindin protein by small interfering RNA (siRNA) resulted in the reduction
of pre-synaptic protein expression and glutamate release, suggesting that
dysbindin might influence exocytotic glutamate release via up-regulation
of the molecules in pre-synaptic machinery. The overexpression of dysbindin increased phosphorylation of Akt protein and protected cortical
neurons against neuronal death due to serum deprivation and these
effects were blocked by LY294002, a phosphatidylinositol 3-kinase (PI3kinase) inhibitor. SiRNA-mediated silencing of dysbindin protein diminished Akt phosphorylation and facilitated neuronal death induced by
serum deprivation, suggesting that dysbindin promotes neuronal viability
through PI3-kinase-Akt signaling.
Conclusion: Genetic variants associated with impairments of these functions of dysbindin could play an important role in the pathogenesis of
schizophrenia.
21
S-01-04
Genetic researches of schizophrenia focusing on Korean
experiences
Tae-Youn Jun
Catholic University of Korea, Dept. of Psychiatry, Seoul, Republic of
Korea
Introduction: Many neuropsychiatric conditions are heritable, which is
one of the best documented facts in biological psychiatry. A lot of data
collected from families, twins and adoptees have consistently supported
the involvement of a major, complex genetic component in liability to
various psychiatric disorders.
Method: During the last three decades, there have been remarkable
advances in the field of genetics in schizophrenia; improved knowledge
of pathophysiology, more valid diagnostic and prognostic methods, and
enhanced specificity in psychopharmacology. Especially, advances in pharmacogenetics expect that it will soon be possible to tailor drug regimens
to the specific genetic makeup of each individual patient and provide
more effective treatments with fewer side effects and less risk of toxicity.
Results: Recently, considerable interests have focused on the long arm of
chromosome 6 where several studies have mapped putative schizophrenia susceptibility loci. Based on an autosomal scan of Arab-Israeli families,
collaborative research groups of Israel and Korea have reported the linkage
of schizophrenia to chromosome 6q23 and about twenty candidate
genes were selected which had potential pathophysiological relevance to
schizophrenia.
Conclusion: In this presentation, I will introduce the genetic studies for
schizophrenia on going in Korea, in various regions including 6q23.
References: Y Kohn and B Lerer (2005) Excitement and confusion on
chromosome 6q: the challenges of neuropsychiatric genetics in microcosm. Molecular Psychiatry 10, 1062-1073
S-03
The atypical psychoses: From psychopathology
to neurobiology
S-03-01
The case for a differentiated nosology of the endogenous
psychoses
Bruno Pfuhlmann
Wrzburg, Germany
Introduction: The Kraepelinian dichotomy of endogenous psychoses into
affective and schizophrenic types has failed to bring about a decisive
breakthrough either in clinical practice or in the scientific study of these
illnesses. The same is true for the anosological views of the currently
used classification schemes, which ultimately base upon Kraepelins
dichotomy. Psychoses that do not fit neatly into this dichotomization are
designated as atypical psychoses, schizophreniform psychoses,
schizoaffective disorders, brief psychotic disorders or acute transient polymorphic psychotic disorders and are assigned to either an
affective spectrum, a bipolar spectrum or a schizophrenic spectrum of psychoses. None of these classifications and diagnostic categories however enables a delimitation of symptomatologically sharply
characterised clinical syndromes with a prognostical significance and an
external validation by means of epidemiological, biological and genetic
findings.
Method: A differentiated nosology of endogenous psychoses may help
to overcome the restrictions and problems of the current classifications
which obviously do not adequately reflect clinical reality. Building on the
earlier work of Wernicke and Kleist, Karl Leonhard elaborated such a differentiated nosology of endogenous psychoses that went far beyond
Kraepelins dichotomy.
Results: Within this nosology the two major groups of endogenous psychoses are subdivided into five nosologically independent disease entities
on the basis of careful cross-sectional and longitudinal observations of a
great number of patients: unipolar affective psychoses, manic-depressive
22
illness, cycloid psychoses, unsystematic schizophrenias and systematic

schizophrenias.
Conclusion: Various clinical, biological and especially genetic findings
suggest that this clinical diversification of endogenous psychoses along
the lines of a differentiated nosology provides seminal perspectives for a
better scientific understanding of the aetiology, prognosis and differential
treatment of the endogenous psychoses.
References: Leonhard K (1999) Classification of endogenous psychoses
and their differentiated etiology. Second, revised and enlarged edition.
Edited by Helmut Beckmann. Springer, Wien, New York.
S-03-02
The cycloid psychoses: A comparison between Leonhard
and Perris diagnostic systems
Victor Peralta
Pamplona, Spain
Manuel J. Cuesta, Sara Chivite, Maria Zandio
Introduction: Cycloid psychoses are mainly conceptualized on the basis
of both Leonhards highly differentiated psychopathological concepts and
the operational diagnostic criteria by Perris & Brockington (P&B).
However, despite the notorious differences between the two diagnostic
systems, they have not been comparatively examined by means of external validity criteria. The aim of this study was to examine the comparative
validity of Leonhard and P&B concepts by means of demographic, familial,
premorbid, clinical and psychopathological variables.
Method: Six-hundred and sixty consecutively admitted psychotic inpatients were administered a battery of instruments to examine clinical variables, symptoms and diagnosis from a polydiagnostic point of view. The
diagnosis of cycloid psychosis was made according to the criteria by
Leonhard and P&B, and the two criteria were compared across a number
of variables including DSM-IV diagnoses, sociodemographic (gender,
age), genetic (familial loading score for schizophrenia and major mood
disorders), premorbid (winter birth, urbanicity, early familial dysfunction,
premorbid adjustment), clinical (age at onset, acute onset (<1week), drug
abuse, lifetime presence of a major affective syndrome, global functioning during the past year, treatment response at the index episode) and
index episode psychopathology.
Results: One-hundred and thirty-seven patients met either Leonhard criteria (n=120) or P&B criteria (n=69). The concordance among the diagnostic systems was moderate (kappa=0.43). The 137 patients were classified as (a) fulfilling the Leonhard but not the P&B criteria (Leonhard
cycloids, n=69, 50.4%), (b) fulfilling the two sets of criteria (n=51,
37.2%) and (c) fulfilling the P&B but not the Leonhard criteria (P&B
cycloids, n=17, 12.4%), and the external variables were examined across
these groups. Compared with the P&B cycloids, the Leonhard cycloids
had higher age at onset (mean=30.2, SD=12.5 vs. mean=22, SD=3.8,
p=0.01), more acute onset (50.7% vs. 23.5%, p=0.029), lower frequency of lifetime mania (15.9% vs. 41.2%, p=0.013) and depression (20.3 %
vs. 52.9%, p=0.008), better treatment response (mean=1.12, SD=0.47
vs. mean=1.47, SD=0.62, p=0.01), less severe negative (mean=1.21,
SD=1.16 vs. mean=2.01, SD=1.57, p=0.027) and depressive symptoms
(mean=0.79, SD=1.54 vs. mean=2.23, SD=2.53, p=0.011) at the index
episode. According to the DSM-IV classification and compared with the
P&B cycloids, in the Leonhard cycloids were underrepresented the diagnoses of schizophrenia (p<0.001) and mood disorders (p<0.001), and
overrepresented the diagnosis of brief psychotic disorder (p=0.002).
Conclusion: Leonhard and P&B diagnostic criteria of cycloid psychosis
seem to represent rather different conceptualizations of the disorder,
since they showed modest concordance and significantly differed across
a number of clinical variables. Compared with the Perris & Brockington
criteria, the Leonhard criteria capture a group of cycloid patients with
higher age at onset, more acute onset, better response to treatment and
less mood symptoms. And most importantly, unlike the Perris &
Brockington criteria the Leonhard diagnosis of cycloid psychosis is framed
in a well-developed nosological system of psychotic disorders.
References: Leonhard K. Differenzierte Diagnostik der Endogen
Psychosen unter Anlehnung an einem Symptommenkatalog. Psychiat
Neurol med Psychol 1990, 3: 136-145. Perris C. The concept of cycloid
psychotic disorder. Psychiat Dev 1988, 1: 37-56.
S-03-03
A controlled family study and a systematic twin study on
cycloid psychoses
S-09
Schizophrenia - a neuroinflammatory disease
Burkhard Jabs
Wrzburg, Germany
Introduction: Cycloid psychoses represent a clinical category which can

be reliably differentiated from schizophrenic and affective psychoses
regarding symptomatology and course.
Method: To further clarify aetiological and nosological questions concerning cycloid psychoses a controlled family study and a systematic twin
study were undertaken. In the family study, all living and traceable adult
first-degree relatives of 45 cycloid psychotic, 32 manic-depressive and 27
control probands were personally examined by an experienced psychiatrist blind to the index probands diagnosis. Age-corrected morbidity risks
were calculated using the life-table method. In the twin study, 22 twin
pairs with cycloid psychotic index twins were systematically recruited in
the psychiatric hospitals of Lower Franconia. After establishing the diagnoses of the respective co-twins by an independent experienced psychiatrist concordance rates were compared.
Results: Relatives of cycloid psychotic patients showed a significantly
lower morbidity risk of endogenous psychoses than relatives of patients
with manic-depressive illness but did not differ significantly from relatives
of controls. In the twin study, concordance rates did not differ significantly
between the 11 monozygotic and the 11 dizygotic pairs resulting in a low
heredity index of 0,21.
Conclusion: Both studies suggest a subordinate role of hereditary
influences in the aetiology of cycloid psychoses. The results point out that
cycloid psychoses have to be distinguished from manic-depressive illness
as well as from schizophrenic psychoses regarding clinical genetic aspects,
and that cycloid psychoses therefore could be integrated neither into a spectrum of schizophrenic psychoses nor into a spectrum of affective disorders.
S-09-01
Immunological aspects of psychiatric diseases
S-03-04
Genetic correlates of catatonia: Periodic catatonia and the
major disease locus on chromosome 15q15
Gerald Stber
Wrzburg, Germany
The clinical significance of catatonic features is obvious and compelling.
According to differentiated psychopathology we propose a differentiation
of the acute remitting catatonic subtypes into motility psychosis and
periodic catatonia. In catatonia a fundamental point is to discriminate
quantitative hyperkinetic or akinetic changes, which are characteristic of
the prognostic favourable motility psychosis, from qualitative changes,
true catatonic signs. Hyperkinetic-akinetic motility psychosis is a phasic
bipolar disorder with psychomotor excitation of expressive and reactive
movements and/or akinesia pole with motor inhibition, particularly of
involuntary movements. The central syndrome in periodic catatonia consists of qualitative psychomotor disturbances in both, a hyperkinetic and
akinetic pole. Psychomotor excitement gives way to iterations and stereotypies, grimacing and parakinesia. On the other pole, prominent symptoms are akinetic negativism as well as distorted stiff movements, masklike facies or posture stereotypies. In most cases acute psychotic attacks
are accompanied by hallucinations and delusions. In remission there
remains a distinct mild to severe catatonic residual state with psychomotor weakness of facial expression and diminished incentive. Videos of
patients suffering from motility psychoses contrasted by those exhibiting
periodic catatonia are presented with discussion of differential diagnoses
and therapeutic strategies. Periodic catatonia (MIM 605419) is genetically mapped to chromosome 15q15 in two independent genome-wide linkage scans on a total sample of 16 multiplex pedigrees. Parametric as well
as haplotype analysis were consistent with the assumption of an autosomal dominant inheritance with reduced penetrance, as reflected by a
morbidity risk of ~27% for first degree relatives. Linkage and haplotype
analysis in three exceptionally large pedigrees linked to chromosome
15q15 disclosed a refined critical region. We are completing a systematic
mutation scan of candidate genes annotated in that region for fine mapping and identification of causative genetic variants. Thus, the findings on
clinical phenotypes of catatonia speak in favour of a nosological classification of catatonia. As a general conjecture in the endogenous psychoses, clinical differentiation creates nosology, and these biological foundations will forge ahead insights in the aetiology.
Markus J. Schwarz
University of Munich, Dept. of Psychiatry, Munich, Germany
Norbert Mller
The impact of an immune process, involved in the pathophysiology of
several psychiatric disorders is currently intensely discussed. One characteristic example is the production of pro-inflammatory and neurotoxic
molecules by activated microglia cells - the resident monocytic immune
cells of the CNS - in Alzheimer's disease (AD). Amyloidogenic amyloidbeta induces the production of quinolinic acid in microglia, which in turn
activates g-secretase and induces phosphorylation of tau protein - two of
the proposed core mechanisms in the pathophysiology of AD. Moreover,
quinolinic acid acts as an agonist at the glycine co-agonist site of the
NMDA receptor, resulting in increased excitotoxicity of neurons.
Additional evidence for the relevance of an inflammatory process in AD
comes from epidemiologic studies, demonstrating the potency of antiinflammatory medication to reduce the risk for developing AD. Another
example for the crucial role of pro-inflammatory cytokines is the induction of depression during IFN-a administration in patients suffering from
hepatitis C or malignant melanoma. These findings are in line with the
sickness behaviour model of Major Depression (MD). This model uses either intraventricular or peripheral application of the pro-inflammatory
cytokines IL-1b, IL-6, TNF-a, or of unspecific immune-activators such as
LPS, which induce depression-like behaviour. In case of peripheral administration, there are several ways for cytokines to enter the brain (e.g. via
vagus nerve, circumventricular organs, or through induction of proinflammatory mediators at the blood-brain barrier). Recent data demonstrate that the increased production of pro-inflammatory mediators may
be accompanied with an enhanced activation of the kynurenine pathway
of tryptophan metabolism, causing a decreased central nervous tryptophan availability, which is the limiting step in serotonin synthesis. Based
on these findings, the selective cyclooxygenase (COX)-2 inhibitor celecoxib has been administered in a placebo controlled add-on study in depressed patients. The results are intriguing, as they demonstrate a significant
improvement of depression symptoms in the celecoxib treated patient
group. The possible involvement of an immune process in the pathophysiology of schizophrenia has been investigated since nearly 100 years.
Although the exact mechanism has not been elucidated yet, there is
strong evidence that a pre- or perinatal infection is accompanied with an
increased risk to develop schizophrenia later on. Experts disagree about
the type of immune activation: Some argue that schizophrenia may be a
kind of autoimmune disorder like rheumatoid arthritis, while others argue
that immune activation in schizophrenia is more similar to an allergic
reaction. A mild chronic immune process in the CNS may anyway result in
the repeatedly reported progressive reduction of brain volume in schizophrenia. Recent data indicate that the endogenous NMDA receptor antagonist kynurenic acid, which is mainly produced by activated astrocytes
(the immunologic opponents of microglia within the CNS), may induce
schizophrenic positive symptoms. COX-2 inhibitors interestingly inhibit
the synthesis of kynurenic acid. Accordingly, administration of celecoxib
was demonstrated to have beneficial therapeutic effects in early stages of
schizophrenia. Altogether, there is strong evidence that inflammatory - or
more generally spoken immune - processes may be crucially involved in
major psychiatric diseases and that anti-inflammatory medication has preventive or therapeutic effects in Alzheimer's disease, major depression,
and schizophrenia.
S-09-02
Rael Strous
Beer Yaakov Mental Health Ctr., Sackler Faculty of Medicine, Tel Aviv,
Israel
23
S-09-03
The precise time of prenatal infection predicts symptom
subtypes in an animal model of schizophrenia
Joram Feldon
Swiss Federal Institute, Behavioural Neurobiology, Schwerzenbach,
Switzerland
Maternal infections during pregnancy increase the incidence of neuropsychiatric disorders with a presumed neurodevelopmental origin in the offspring, including schizophrenia and autism. However, this association
appears to be critically dependent on the precise times of the prenatal
infectious events. In particular, the long-term functional consequences of
prenatal immune activation at different times of gestation may be related
to differing symptom cluster of schizophrenia. In order to study the temporal dependency in an animal model of prenatal viral-like infection in
mice, we administered pregnant dams on gestation day (GD) 9 or GD17
with the viral mimic polyriboinosinic-polyribocytidilic acid (PolyI:C;
5mg/kg, i.v.) or vehicle solution. The resulting adult offspring were then
tested in a number of behavioral and pharmacological paradigms relevant
to the positive-negative dichotomy and cognitive symptoms of schizophrenia. Our findings here and in previous reports (Brain Behav. Immun.
20:378-388, 2006; J. Neurosci. 26:4752-4762, 2006) thus indicate that
prenatal immune activation in early/mid pregnancy leads to a variety of
abnormalities associated with positive symptoms of schizophrenia,
whereas prenatal immune activation in late gestation results in the emergence of behavioral and pharmacological dysfunctions particularly associated with negative and cognitive symptoms of this disorder.
S-09-04
Schizophrenia-like cognitive and social deficits seen in
adult offspring following prenatal maternal immune
activation can be prevented by N-acetylcysteine
Ina Weiner
Tel Aviv University, Faculty of Social Sciences, Israel
Introduction: Maternal exposure to infection during pregnancy is associated with increased liability to schizophrenia in the offspring, and it has
been proposed that elevation of pro-inflammatory cytokines in the maternal host in response to infection is the key factor for fetal brain maldevelopment. The latter has inspired the development of the prenatal immune
challenge model of schizophrenia in which the synthetic cytokine releaser
polyinosinic-polycytidilic acid (PolyI:C) is used to activate the maternal
immune system. Adult offspring of poly I:C treated dams exhibit many
phenotypic features reflective of schizophrenia, including impaired sensorimotor gating and attentional selectivity, increased dopamine function,
hippocampal pathology, and responsiveness to antipsychotic drugs. Here
we evaluated whether poly I:C-induced behavioral abnormalities could be
prevented by N-acetylcysteine (NAC, antioxidant and glutathione precursor) which was shown to block inflammatory cytokine elevation in maternal serum and fetal brains induced by the lipopolysaccharide endotoxin
(LPS).
Method: Pregnant rats were injected on gestational day 15 with vehicle,
poly I:C (4mg/kg), NAC (1.5 or 15mg.kg) or poly I:C+NAC. Their offspring
were tested at adulthood in two tasks measuring selective attention,
latent inhibition and discrimination reversal, and in social interaction.
Results: Compared to adult offspring of dams treated with vehicle, adult
offspring of poly I:C treated dams exhibited impairment of selective attention as manifested in loss of latent inhibition and abnormally rapid reversal, as well as reduced social interaction. Co-treatment with NAC at
15 mg/kg prevented the poly I:C-induced deficits in all three tasks.
Conclusion: Prenatal poly I:C-induced hallmark deficits associated with
schizophrenia, attentional and social, supports the hypothesis that immune
activation during pregnancy may in part be responsible for the interaction
between maternal infection during pregnancy and schizophrenia.
Furthermore, this is the first demonstration of in utero benefit of NAC
treatment in protecting from long term behavioral abnormalities resulting
from pregnancy complicated by maternal infection. Since NAC has low
toxicity and is approved for use in humans, this may have implications for
early prevention.
References: Buhimschi et al (2003) Am J Obstet Gynecol 188:203-8
Meyer et al (2005) Neurosci Biobehav Rev 29: 913-947 Pahan et al (1998)
24
Free Radic Biol Med 24:39-48. Patterson PH, Nawa H (1993) Cell 72:12337 Zuckerman L, Weiner I (2005) J Psychiatric Res 39:311-323 Zuckerman
et al (2003) Neuropsychopharmacology 28:781-789. Xu et al (2005)
ToxSci
S-12
Pathophysiological mechanisms indicate that
schizophrenia is a systemic disorder
S-12-01
Schizophrenia as a disorder of the membrane phospholipids
Wagner Gattaz
Sao Paulo, Brazil
Introduction: Disordered membrane phospholipid metabolism has consistently been described in schizophrenia. The most robust findings are
the reports of increased activity of phospholipase A2 (PLA2) in the blood
an in the brain of schizophrenic patients, as PLA2 is the key enzyme in the
metabolism of membrane phospholipids. These findings are in line with
the results from studies using 31P-Magnetic Resonance Spectroscopy
(MRS), which reported on abnormalities in frontal lobe metabolism in
schizophrenia, expressed as a reduction in the resonances of phosphomonoesters (PME) and/or increased phosphodiesters (PDE), which are respectively the precursors and the metabolites of membrane phospholipids,
suggesting thus an accelerated phospholipid metabolism in the disease.
Other studies reported increased high-energy phosphate (ATP-adenosine
triphosphate and PCr - phosphocreatine) in schizophrenia, reflecting
decreased use of energy in the frontal lobe.
Method: We investigated 53 schizophrenic patients (DSM-IV) and 35
healthy controls. Eighteen from these patients were drug-nave, and the
remaining 35 were drug free for an average of 6 months. Phospholipid
metabolism and high-energy phosphates were assessed in the left frontal
lobe using 31P-MRS. Psychopathological evaluation was done with the
Brief Psychiatric Rating Scale and the Negative Symptoms Rating Scale.
Neuropsychological evaluation was performed with the Wisconsin Card
Sorting Test, Stroop Test, and Wechsler Adult Intelligence Scale.
Results: Drug-nave patients showed reduced PDE in left frontal lobe
compared to controls and to previously medicated patients (p < 0.05). No
differences among the 3 groups were found regarding the other spectroscopy parameters. In healthy controls, but not in schizophrenics, a
negative (and probably physiological) correlation was found between
PME and PDE (p < 0.01). In schizophrenic patients ATP was correlated
with negative symptoms and with neuropsychological impairment (p <
0.01).
Conclusion: The lack of a correlation between PME and PDE, as well as
the reduction of PDE in schizophrenia suggest a disrupted phospholipid
metabolism in the disease, albeit in the contrary direction of that reported in the literature. The relationships of ATP with negative symptoms and
neuropsychological deficit suggest an alteration of energetic demand in
the frontal lobe of schizophrenic patients, which is in line with the
hypofrontality hypothesis of the disease.
S-12-02
Membrane phospholipid deficits and therapeutic
implications in schizophrenia
Jeffrey Yao
VA PGH Healthcare Systems, Building 13, Pittsburgh, PA, USA
Introduction: While many ideas regarding schizophrenia (SZ) pathogenesis have been put forth, the majority of research has focused on neurotransmitter function, particularly in relation to altered dopamine activity.
However, treatments based on this paradigm have met with only modest
success, and current medications fail to alleviate symptoms in 30-60% of
patients. Multiple lines of evidence to date implicate the lipid environment in the behavior of neurotransmitter systems.
Method: Membrane lipids and polyunsaturated fatty acids (PUFAs) were

measured by high-pressure liquid chromatography with evaporative lightscattering detector, capillary gas chromatography with flame ionization
detector, and a multi-voxel 31P Magnetic Resonance Spectroscopy (MRS).
Results: Results: Decreased membrane phospholipids (PLs) and PUFAs
have been demonstrated in both brain and peripheral membranes in SZ,
which is consistent with the recent hypothesis of myelin-related dysfunction
in SZ. These differences appear to be independent of neuroleptic treatment, and are associated with illness severity. The accelerated breakdown
of membrane PLs is supported by the 31P MRS findings in brains of SZ
patients. Moreover, a significant correlation was found between RBCPUFAs and 31P MRS measures of PL metabolites in the frontal lobe. Both
increased oxidative stress and altered immune function may be responsible for increased PLs breakdown. Given the diverse physiological function
of membrane PLs and PUFAs, an elucidation their role in SZ pathophysiology may provide novel strategies in the treatment of this disorder. Recent
studies suggest that the adjunct treatment of omega-3 fatty acids may be
beneficial in reducing symptom severity as well as coronary artery disease
risk in SZ patients.
Conclusion: In short, it is unequivocal that a balanced essential fatty acid
diet is important, particularly during the early stages of brain development. On the other hand, to determine whether membrane PUFA deficits
are of primary etiological significant in these psychiatric disorders will
require further investigation. Since a variety of apparently disparate biological findings have been reported, very likely there is etiologic heterogeneity that exists a final common pathogenics pathway which mediates
the recognizable clinical syndroms. Nonetheless, there is sufficient evidence to support large-scale systematic clinical trails of adjunctive omega-3
fatty acids supplementation to modify the course and severity of schizophrenia.
S-12-03
Tyrosine transport studies indicate that schizophrenia
comprises hypodopaminergic fucntioning
Nikolaos Venizelos
Orebro University, Clinical Medicine, Biomed., Orebro, Sweden
L. Flyckt, G. Edman, L. Bjerkenstedt, F. Wiesel
Introduction: Data will be presented that supports a basically decreased
dopamine activity in schizophrenia. Tyrosine is a precursor to dopamine
and is involved in partial regulation of dopamine synthesis. Competitive
transport of tyrosine across the blood brain barrier (BBB) with other amino
acids can cause a limited availability of tyrosine to the brain. Transport of
neutral amino acids including tyrosine and alanine, mainly occurs through
L and A system. To find out if there is an altered availability of tyrosine in
schizophrenia, two main study lines were conducted. One in vitro, in
which the tyrosine kinetics was investigated threefold in cultured fibroblasts from different patients with schizophrenia and controls and the
other by twofold studies in vivo, across the BBB with Positron Emission
Tomography (PET).
Method: In order to study in vitro tyrosine transport we have taken skin
biopsies (in 3 different studies) and cultured fibroblasts from patients with
schizophrenia and controls. With the cluster tray method tyrosine flux
across the cell membrane was determined by L-14C-tyrosine in 12 different concentrations of tyrosine. From the obtained data tyrosine kinetics
(Vmax, Km) were calculated. For in vivo studies we used PET to study the
transport of tyrosine from blood into the brain, i.v. injection of L-11Ctyrosine was used as a tracer.
Results: In 3 distinct studies, reduced tyrosine transport across the fibroblast membrane has been shown with lower maximal transport capacity
(Vmax) and affinity constant (Km). PET-studies did also demonstrate lower
and different regulation of tyrosine influx over the BBB in schizophrenics.
Moreover, clinical validation of aberrant tyrosine transport in schizophrenics was demonstrated by the finding of a correlation between a lower
Km for tyrosine and poorer cognitive functioning.
Conclusion: In vitro and in vivo findings give strong evidence that tyrosine
transport is aberrant in patients with schizophrenia. The importance of
this finding is two fold. Changes in tyrosine transport may be due to an
aberrant cell membrane function that may cause widespread changes
both in neurotransmission and psychopathology in schizophrenics.
Secondly changes in tyrosine availability may influence dopamine func-
tion. Our research strongly supports the view that schizophrenia basically
is a hypodopaminergic condition.
S-12-04
Dysregulation of basal metabolic rate in patients with
schizophrenia
Frits-Axel Wiesel
Uppsala University, Neuroscience Psychiatry, Sweden
Introduction: Measurements of basal metabolic rate in patients with
schizophrenia have indicated lower energy expenditure. This observation
may explain the apathy, avolition and over-weight so often seen in
patients. Importantly these measurements were made before the introduction of the neuroleptics. However, the methodology used may be
questioned which motivates new studies to elucidate energy expenditure
in patients with schizophrenia.
Method: Patients (n=30) were consecutively recruited from clinical settings. Ten patients were neuroleptic naive (first episode). The control
group consisted of healthy participants (n=17) matched for age and gender. After a night fasting the participants were transported by car to the
laboratory where resting energy expenditure (REE) was determined with
indirect calorimetry. Body composition was measured by the use of bioelectrical impedance (BIA).
Results: No significant differences in body weight, BMI, age, or laboratory
data were found. Obtained respiratory energy expenditure data and
anthropometric data were modelled according to FAO/WHO/UNU equations and predicted levels were compared with observed data. The difference between observed and predicted REE was larger (p<0.02) in the
patients i.e. they had a lower REE than predicted. This was also the case
in neuroleptic naive patients. BIA demonstrated that patients had significantly lower percentages of water in fat free mass and intracellular water.
Conclusion: Our main finding was a lower REE in patients with schizophrenia and this was also observed in neuroleptic free patients. Moreover
the results could not be explained by differences in age, BMI, body temperature or levels of thyroid hormones. Importantly the highly metabolic
compartment of fat free mass did not differ between patients and controls. It may be speculated that lower REE is connected with a disturbance
in membrane function. Changes in membrane phospholipids will influence
by many things receptor function and highly energy demanding mechanisms for ion transport across the membrane. In all the findings indicate
disturbances in homeostatic regulatory mechanisms in schizophrenia.
References: Nilsson BM, Forslund AH, Olsson RM, Hambraeus L, Wiesel
F-A. Differences in resting energy expenditure and body composition
between patients with schizophrenia and healthy controls. Acta
Psychiatraica Scandinavica 2006:114;27-35.
S-20
Deconstructing psychosis: Developments for
future classification
S-20-01
The concept of endo-phenotypes
Wolfgang Wlwer
University of Duesseldorf, Dept. of Psychiatry, Duesseldorf, Germany
Franz J. Mller-Spahn, Universitaere Psychiatrische Kliniken, Germany
Schizophrenia is a complex neurobiological disorder with heterogeneous
genetic and pathophysiological components that requires the use of multidisciplinary strategies. The disorder is characterized by a broad spectrum
of symptoms including severe impairments in crucial aspects of cognitive
function. Negative symptoms and cognitive deficits impair substantially
psychosocial functioning. A new approach to overcome the complexity of
the disease is to separate schizophrenia into its neurobehavioral subcomponents, termed intermediate phenotypes (Friedman J and Davis K, Biol
Psychiatry 2006; 60: 527-529) or "endophenotypes". Gottesman H and
Gould TD (Am J Psychiatry 2003; 160: 636-645) developed 5 criteria for
25
identifying useful endophenotypes in psychiatry: (1) association with illness in the population; (2) heritability; (3) state independence; (4) within
families, the endophenotype and the illness should co-segregate; and (5)
the endophenotype should be found in unaffected family members at a
higher rate than in the general population. Thus endophenotypes help to
clarify the "upstream" traits underlying clinical, as well as the "downstream" biological consequences of genes (Hasler et al., Biol Psychiatry 2006;
60: 93-105). The current definitions of psychiatric disorders are based on
clinical experience and conventions and are not biologically valid.
Endophenotypes are different from diagnostic markers. Cognitive deficits,
e.g. attention deficits, deficits in verbal learning and memory and executive functioning may index genetic liability for schizophrenia. A recent
metaanalysis on cognitive deficits in unaffected first-degree relatives of
schizophrenia patients indicated reliable relative-control differences with
the largest effect sizes found in continuous performance task, auditory
verbal learning, design copy test and category fluency (Snitz B et
al.,Schizophrenia Bulletin 2006; 32: 179-194). A significant association
was found between variants in the dysbindin gene (DTNBP1) and negative symptoms (DeRosse P et al., Am J Psychiatry 2006; 163: 532-534).
There is some evidence indicating that schizophrenia patients use an inefficient encoding and retrieval strategy (MacDonald A et al., Am J
Psychiatry 2005; 162: 475-484). Nicotine may improve abnormal smooth
pursuit eye movement in schizophrenic patients through cholinergic stimulation of the hippocampus and cingulate gyrus (Tanabe J et al., Biol
Psychiatry 2006; 59: 754-751). A survey of clinical, neurobiological and
genetic studies to evaluate candidate endophenotypes for schizophrenia
will be presented. This includes neuropsychological, cognitive, neurophysiological, neuroanatomical, neuroimaging and biochemical measures.
S-20-02
The ultimate goal: A modular approach to psychosis
Wolfgang Gaebel
University of Duesseldorf, Psychiatry and Psychotherapy, Germany
Introduction: The ultimate goal: A modular approach to psychosis
Wolfgang Gaebel, Jrgen Zielasek Department of Psychiatry and
Psychotherapy, Heinrich-Heine-University, Rhineland State Clinics,
Bergische Landstr. 2, D-40629 Duesseldorf, Germany Introduction
Neurobiological methods like functional magnetic resonance imaging and
genetic methods like the analysis of polymorphisms in genes conferring
an increased risk to develop a psychotic disorder necessitate a rethinking
of our current psychiatric classification systems. Still, there is a large gap
between neuroscientific findings, for example in genetics or other types
of endophenotypes, and the clinical phenomenology. However, it will be
crucial to understand how environmental insults and genetic factors interact in individual patients to finally result in psychotic disorders. According
to the biological approach in psychiatry, these factors will exert their action
on final common pathways, namely the neural substrates of the physiological functions of the brain. New theoretical frameworks based on current advances in psychobiology are needed to unify information from psychobiology, neurobiology and clinical phenomenology.
Method: We reviewed whether concepts of modularity derived from the
psychological sciences and neurosciences may be useful as a theoretical
framework for future diagnostic classifications.
Results: We describe how dynamic networks of functional subunits of
the brain may act as the substrates for noxious factors leading to psychotic phenomenology. We will discuss how such a theoretical framework
may help to bridge the gap between neurobiological and psychological
findings and clinical psychiatry. This will imply a functional approach
towards psychopathology as the main method both for psychiatric classification and research purposes. Also, treatment may be guided by thinking in functional subunits of the brain and we will discuss affect recognition in schizophrenia as one example of how a modular approach may
lead to a modular diagnosis and modular therapy. We will discuss the pros
and cons of a modular approach to psychosis regarding theoretical foundations, research applications, and clinical feasibility.
Conclusion: A modular approach towards psychotic disorders based on
findings in neurobiology and psychology can guide both research and
clinical classification including treatment of psychotic disorders. However,
much research work is still to be done in order to identify the presumed
functional subunits of the brain, their interactions, and their roles in the
pathophysiology of psychiatric disorders.
26
S-20-03
Syndrome with psychosis - the evidence from multivariate
statistics
Peter McKenna
University of Glasgow, Psychological Medicine, United Kingdom
Introduction: Controversy over the status of schizophrenia goes back to
the time of Kraepelin, who stated, the assertion that this is a distinct disease has met with repeated and decided opposition. Debate has
focused particularly on its distinction from manic-depressive psychosis.
Method: The first generation of studies applying multivariate statistics to
samples of unselected psychotic patients had uncertain results. Factor
analytic studies tended to produce factors consistent with mania and
depression, but the schizophrenia-related factors which emerged were
multiple and less than intuitive. Cluster analytic studies broadly failed to
segregate most patients into schizophrenic and affective categories. An
influential discriminant function analysis by Kendell from this era also
failed to provide clear evidence of bimodality. However, a less well-known
series of discriminant function analyses performed as part of the WHO
International Pilot Study of Schizophrenia produced a remarkably clear
separation of the two forms of psychosis.
Results: Contemporary studies may be able to resolve some of the uncertainties surrounding earlier studies. Recent factor analytic studies have all
continued to isolate mania and depression factors, plus schizophrenic factors which are broadly recognisable as Liddles positive, negative and disorganisation syndromes. Cluster analysis generates mutually exclusive
subgroups of individuals within a population, which is arguably appropriate for psychosis where mixed forms of presentation are common.
Techniques such as Grade of Membership analysis, which avoid this difficulty, have had more success in segregating the two forms of psychosis.
Conclusion: Multivariate statistics, contrary to its bad press, has always
supported the view that the distinction between schizophrenia and
manic-depressive psychosis carves psychosis at its natural joints.
S-20-04
Exclusion criteria of stimulant-induced psychosis for diagnosis of schizophrenia
Mitsumoto Sato
Tohoku Fukushi University, Sendai, Japan
Introduction: Methamphetamine (MAP) is a representative illicit drug
abused widely in Japan since 1940s. Most abusers inject or inhale high
purity MAP once or several times a day for long time. The onset, course
and outcome of MAP-induced psychosis have been studied to define the
disease concept in Japan (Sato et al. 1992), which is difficult to distinguish
from schizophrenia using diagnostic criteria of ICD-10 and DSM-IV.
Method: The literatures that studied onset, course and outcome of stimulants (amphetamine and MAP)-induced psychosis are reviewed to define
natural course of stimulant-induced psychosis. In addition, neurobiological studies on stimulants-induced behavioral hypersensitivity are reviewed
to discuss a lasting change in the brain dopamine systems.
Results: Essential features of MAP-induced psychosis which initial onset
is during MAP abuse are prominent hallucinations and delusions with
remarkable suspicion. The delusions are often bizarre, and hallucinations
consist of a voice keeping up a running commentary on the persons
thought and behavior. The most striking point is that stimulant-induced
psychosis indistinguishable from schizophrenia may persist even after discontinuation of MAP (over 10 days in 36%, over 1 month in 13-23%) of
the patients. As it persists after excretion of MAP from the body, it is not
judged to be due to the direct physiological effects of MAP. In experimental study, lasting sensitization to amphetamine, MAP and cocaine after
repeated administration has been well documented. Candidate genes
related to development, maintenance and recurrence of the sensitized
abnormal behavior has been reported by Ujike at al(2003).
Conclusion: The psychosis similar to schizophrenia which initial onset is
during stimulant abuse and persist beyond the period during which a
direct stimulant effect reasonably be assumed to be operation should be
included into Residual and Late-Onset Psychotic Disorder (F1x.7) and
excluded from schizophrenia. It seems necessary to clarify the concept of
schizophrenia and useful for generating treatment guideline for schizophrenia co-morbid with stimulant abuse.
References: 1. Sato M, Numachi Y, Hamamura T: Relapse of paranoid

psychotic state in methamphetamine model of schizophrenia.
Schizophrenia Bull, 18: 115-122, 1992 2. Ujike H, Hrano M, Inada T et al:
Nine- or few repeat alleles in VNTR polymorphism of the dopamine transporter genes is a strong risk actor for prolonged methamphetamines psychosis. Pharmacogenomics J, 3: 242-247, 2003
S-24
HPA - axis dysregulation, glutamatergic pathways and cytokines in major psychoses: An
updating
S-24-01
Molecular mechanisms for the involvement of cytokines in
psychiatric conditions: New evidence
Alberto Clivio
University of Milano, Dept. Preclinical Sciences, Milan, Italy
Mario Clerici, Carlo Altamura, Emanuela Mundo, Daria Trabattoni,
Barbara Arosio, Carlo Lorenzo Cazzullo
Introduction: Current paradigms in immunology propose that extensive
sharing of soluble molecules and cell-associated receptors reveal a strong
cross-talk between the immune and the nervous systems, in which even
the autoimmune component plays a role in nervous system development
and homeostasis. The interaction between these systems is not only active
at the molecular level, but at the cellular level as well: immune competent
T cells seem to play an important role in the development and maintenance of a proficient nervous system. We checked the cytokine response
in schizophrenic subjects and in unipolar as well as bipolar depression.
Method: ELISA ELISPOT DNA genotyping
Results: Schizophrenia: we found that the psychopathological status of
the patients as assessed by PANSS was worst in subjects with a reduced
IL-10 response and a higher IL-6/TNFalpha response, and that the
response to risperidone therapy correlated well with normalisation of the
cytokine profile. Different neuroleptics gave a different clinical outcome
and immunological profiles. Depression: We found that in subjects with
unipolar depression the frequency of the allele G of MCP-1 was significantly higher than in the general population and this genotype correlates
well with an earlier age of onset.
Conclusion: Immunological parameters such as the TH1/TH2cytokine
profile can be used to monitor the therapeutic outcome of schizophrenia
in patients treated with neuroleptics and constitutes a suitable biological
parameter for the assessment of therapeutic success.
S-24-02
Cytokine abnormalities in major depression
Emanuela Mundo
University of Milan, Clinical Sciences Luigi Sacco, Italy
Elisabetta Cattaneo, Sara Pozzoli, Mario Clerici, Daria Trabattoni,
Beatrice Arosio, A. Carlo Altamura
Introduction: The neuro-immune-endocrine cross-talk is impaired in in
schizophrenia and mood disorders, particularly in Major Depression (MD)
(1, 2). The aim of this presentation is to critically review recent studies on
the role of cytokines in MD.
Method: Studies on cytokine plasma levels and genetic studies on
cytokine gene polymorphisms will be considered. In addition, original
data on the role of cytokine gene polymorphisms in conferring susceptibility to MD will be presented.
Results: Altered inflammatory responsiveness has been found in MD
(2, 3), with an increase of PGE2, IL-1, IL-2, and IL-6 (4). In addition, the
increase of some cytokine levels, e.g., IL-1 and IL-6, may induce symptoms
that resemble depressive symptoms (5) and it may also stimulate the HPA
axis and the production of CRF (5). A recent study has shown that
patients with MD and increased early life stress have an enhanced inflammatory responsiveness to psychosocial stress (2). These results provide evidence for a link between MD, early life stress, and diseases associated
with inflammatory response (2). Some studies have also found that anti-
depressants may decrease some cytokine levels (e.g., IL-12 and TGF-beta 1)
(3, 5). However, the relationship between cytokine plasma levels and antidepressant response is still unclear.
Conclusion: Cytokine levels and cytokine gene polymorphisms appear to
be related to susceptibility to MD. Future studies should focus on the role
of cytokines in mediating the pharmacological response to antidepressants and the recurrence of depressive episodes. Differences between
unipolar and bipolar depression with respect to altered inflammatory
responsiveness and cytokine system should be also investigated.
References: 1. Altamura AC, Boin F, Maes M. HPA axis and cytokines dysregulation in schizophrenia: potential implications for the antipsychotic
treatment. Eur Neuropsychopharmacol 1999; 10: 1-4. 2. Pace TW,
Mletzko TC, Alagbe O, Musselmann DL, Nemeroff CB, Miller AH, Heim
CM. Increased stress-induced inflammatory responses in male patients
with major depression and increased early life stress. Am J Psychiatry
2006; 163(9): 1630-1633. 3. Lee KM, Kim YK. The role of IL-2 and TGFbeta1 in the pathophysiology of major depressive disorder. Int
Immunopharmacol 2006; 6(8): 1298-1304. 4. Maes M. Evidence for an
immune response in major depression: a review and hypothesis. Progr
Neuropsychopharmacol Biol Psychiatry 1995; 19(1): 11-38 5. Dantzer R.
Cytokine-induced sickness behavior: mechanisms and implications. Ann N
Y Acad Sci 2001; 933: 222-234.
S-24-03
Xiang Zhang
Baylor College of Medicine, Psychiatry, Houston, USA
S-24-04
Epigenetics and psychiatric disease: What a small DNA
modification may mean to complex phenotype
Arturas Petronis
Centre for Addiction and Mental Health, Toronto Ontario, Canada
Introduction: Despite significant progress in human genetics, the identification of the molecular basis of inherited predisposition to complex nonMendelian diseases such as major psychosis, diabetes, and cancer, is more
complicated than cloning the genes for simple Mendelian disorders. The
slow progress of research in complex diseases may be due to limitations
in the dominating etiological paradigm that nominates DNA sequence
variation as the single mechanism for inherited predispostion.
Method: We argue that, compared to DNA sequence-based factors, epigenetic modifications of DNA and histones can better explain the various
non-Mendelian irregularities of complex diseases. Partial meiotic stability
of epigenetic factors is consistent with the unclear mode of inheritance of
complex disease, while partial mitotic stability of epigenetic regulation
sheds new light on the molecular mechanisms of discordance of monozygotic twins, critical age of onset, sex- and parent-of-origin- effects, and
the fluctuating course of many complex diseases.
Results: Our DNA methylation analysis using 12,192 feature CpG island
microarrays revealed a number of genes that exhibit epigenetic differences in post-mortem brain tissue from major psychosis patients compared
to unaffected control samples. In addition, our detailed epigenetic analysis
of the male germline revealed surprisingly high intra-individual variation,
which may shed a new light on the controversial concept of non-shared
environment.
S-25
Affective dysfunctions in schizophrenia
S-25-01
Assessment of impairments and treatments in schizophrenia - are we beyond positive symptoms?
Veronica Larach-Walters
Psychiatry, Santiago, Chile
Everyday practice and treatment of schizophrenia has focused mainly on
positive symptoms, in spite of our present knowledge about the different
symptom domains and their relevance to outcome. Treatment targets
27
should comprise - beyond positive symptoms -negative and affective

symptoms, cognitive, social and work dysfunction and quality of life
improvement. Patients are still very insufficiently assessed specifically for
every one of these aspects if at all, and not treated for these issues in
everyday practice, public or private. This is specially striking regarding
social competence and acquisition or preservation of social skills.New
atypical antipsychotics, have significantly diminished extrapyramidal sideeffects. with low - if any - motor side effects and may exert a modest
favourable influence on primary negative symptoms, influencing motor
and affective behavior and expression Also new psychological treatment
strategies targeting psychosocial and cognitive domains may help to
improve social functioning and quality of life. These new treatment strategies and target domains introduce the need of extensive training and
modernization of impairment assessment and rehabilitation techniques.
There are, well established evidence of their importance for integral
recovery. We will stress the facts behind these deficiencies, not only
because of academic rigor, but because of its serious implications for
treatment, psychosocial functioning, prognosis and therefore stigma for
both patients and their families.
S-25-02
Affect expression - impairements and teatment
Wolfgang Gaebel
University of Duesseldorf, Psychiatry and Psychotherapy, Germany
Impairments in affect expression in schizophrenia engage psychiatry since
more than 100 years. According to DSM-IV affective dysfunctions are
defined in terms of non-verbal characteristics (signs) that are indicators of
subjective feeling states. Often such dysfunctions manifest as affective
flattening which is recorded by means of rating scales relying on more or
less systematic observation. To overcome potential rating biases (e.g. rating
tendencies, Halo-effects), the scientific approach to affective deficits
should make use of more systematic and objective behavioral assessment
methods. Because of the superior data quality those data are more suitable as psychopathological starting points for studying brain-behavior
relationships. By using this kind of approach results from our own studies
demonstrate that, despite of broad overlap in clinical rating scales, distinct behavioral patterns comprising facial activity, gestures, voice pitch,
speech activity, can be identified in schizophrenia and depression. In contrast, rating scale data proved to be less reliable, more unidimensional
and of less predictive value for the clinical course. The question whether
such an approach helps to investigate effects of new treatment (e.g. new
antipsychotics) with regard to their impact on negative symptoms, which
often proved to be difficult to treat, remains open yet. An example of a
currently conducted study designed to contribute to this question will be
presented.
S-25-03
Affect recognition - impairments and treatment
Wolfgang Wlwer
University of Duesseldorf, Dept. of Psychiatry, Germany
Introduction: Impairments in affect recognition are well known in schizophrenia and seem to play a crucial role in patients poor social functioning. In particular impairments in facial affect recognition are known to
be a trait-like characteristic in schizophrenia mostly unaffected by traditional treatment. An overview on the evidence on impairments in affect
recognition in schizophrenia will be given and new strategies to overcome
these impairments will be described using an own study as example
Method: A special Training of Affect Recognition (TAR) was evaluated
using a pre-post-control group design with three groups of partly remitted schizophrenia patients. To control for nonspecific effects of implicit
cognitive training, TAR was compared with a Cognitive Remediation
Training (CRT) aiming at improvement of basic neurocognitive functioning. To control for nonspecific effects the two active training groups
were compared with a control group without additional training (CG).
Results: Patients under TAR showed an improvement in facial affect
recognition, with recognition performance after training approaching the
level of healthy controls from former studies. Patients under CRT and
those without training (CG) did not show improvements in affect recognition, though patients under CRT improved in some memory functions.
28
Conclusion: Thus, improvements in disturbed facial affect recognition in

schizophrenia patients is not obtainable with a traditional cognitive remediation program like CRT, but needs a functional specific training like the
newly developed TAR.
References: Wlwer W., Frommann N., Halfmann S., Piaszek A., Streit
M., Gaebel W. (2005) Remediation of impairments in facial affect recognition in schizophrenia: Efficacy and specificity of a new training program.
Schizophr Res. 80: 295-303
S-25-04
Neural correlates of impaired affect regulation in schizophrenia
Raquel Gur
University of Pennsylvania, Psychiatry, Philadelphia, USA
J. Loughead, C. Kohler, M. Elliott, C. Gur, James Loughead, Christian
Kohler, Marc Elliott
Introduction: Flat affect has long been recognized as a central symptom
of schizophrenia that portends poor outcome. Advances in neuroscience
enable examination of neural processes associated with affective dysfunction in schizophrenia. We found that patients with flat affect show
greater clinical impairment and deficits in verbal memory and in emotion
identification. The role of amygdala and other limbic structures has been
examined in fMRI studies that report increased amygdala activation for
fearful or threatening stimuli, with more mixed results on other emotions.
Patients with schizophrenia show impairment in emotion identification
tasks and reduced amygdala activation while performing such tasks.
However, there is limited knowledge on how schizophrenia affects the
brains response to the appearance of emotional faces and how this
relates to performance.
Method: We examined flat affect in a series of studies integrating clinical,
neurocognitive and emotion processing measures. The clinical measures
included assessment of negative symptoms. The neurocognitive and emotion processing measures included computerized tasks that examine
several domains including attention, abstraction and mental flexibility,
memory and emotion identification. We conducted a series of event-related
fMRI studies using happy, sad, angry, fearful and neutral faces.
Results: We found that patients had reduced amygdala activation for
emotion identification tasks. However, its activation in patients and controls showed opposite associations with performance depending on the
specific emotion. For threat related emotions of anger and fear, greater
amygdala activation in controls was associated with correct identification,
while in patients greater amygdala activation portended incorrect responses.
This paradoxical effect was highly correlated with severity of flat affect.
Conclusion: These results suggest that affective blunting in schizophrenia relates to overactivation of the amygdala in response to threatening.
References: Gur RE, Kohler CG, Ragland JD, Siegel SJ, Lesko K, Bilker
WB, Gur RC. Flat affect in schizophrenia: Relation to emotion processing
and neurocognitive measures. Schizophrenia Bulletin, 2006, 32, 279287. Gur RE, McGrath C, Chan RM, Schroeder L, Turner T, Turetsky BI,
Kohler C, Alsop D, Maldjian J, Ragland JD, Gur RC. An fMRI study of
facial emotion processing in schizophrenia. American Journal of
Psychiatry, 2002, 159, 1992-1999.
S-29
Into the secrets of schizophrenia
S-29-01
Progressive brain changes
Lynn DeLisi
New York University, Psychiatry, USA
Introduction: Schizophrenia is a chronic progressive disorder that has at
its origin structural brain change in both white and gray matter. It is likely
that these changes begin prior to the onset of clinical symptoms in cortical regions particularly concerned with language processing. Later they
can be detected by progressive ventricular enlargement. Ventricular

enlargement, presumably indicative of regional cortical tissue reduction
has long been reported in patients with chronic schizophrenia since the
early pneumoencephalographic literature, then later by CT and MRI.
Currently several longitudinal follow-up MRI studies of 1st episode and
chronic patients have been reported. However, the data are inconsistent
across studies. While ventricular enlargement appears to be present at the
first episode, it also appears to continue to enlarge regardless of when
patients are studied and detected in short time intervals. Similarly frontal
and temporal lobe, hippocampus, and superior temporal gyrus have been
shown in some short interval follow-ups to decrease over time.
Method: A longitudinal study through 10 years of follow-up was performed of individuals who had a 1st episode of schizophrenia. All subjects
had serial MRI scanning and cognitive testing. Currently individuals are
being studied at high genetic risk for schizophrenia before they develop
symptoms
Results: In the first 5 years of illness, significantly greater ventricular
enlargement, whole brain and cerebellar volume reductions were detected than appeared in controls. From years 5 to 10, approximately onethird of the patient group showed further ventricular enlargement,
although not whole volume change compared with controls. No temporal or superior temporal gyrus changes were seen over the 10 year period.
In addition no clinical correlations to continual ventricular expansion or
temporal lobe reduction could be found. Although verbal and non-verbal
memory worsened over time, this change was uncorrelated with any
structural brain changes. Individuals at high genetic-risk for illness are
already showing subtle signs of brain stuctural and functional deviation.
Conclusion: Thus, while some progressive structural brain change is active
in chronic schizophrenia and occurs after the onset of illness, its cause is
unknown and may not be clinically relevant or a clue to the core pathogenesis of this disorder. However, it is now possible to use current MRI
technology to provide a valuable tool for detecting early changes of cortical atrophy and anomalous language processing that may be predictive
of who will develop schizophrenia before the full-blown illness is present.
S-29-02
Schizophrenia: When energy matters
Carlos Hojaij
The Melbourne Institute of Biological Psychiatry, Balwyn, Melbourne,
VIC, Australia
More than one century research on Schizophrenia still does not respond
to the question of which biological markers could identify the disease,
and even less what is causing the disease. If, from one hand, psychopathological phenomena continue insufficient to guarantee a
straightforward diagnosis, data from neuroscience just make correlations
with some symptoms of the disease, a point much behind the explanation of the whole disease. It is intriguing the schizophrenia explanation
resistance. Heuristically one could accept the idea that things are happening in a field not yet subject to a objective observation, like the process
occurring at an energetic level in the brain. In this presentation consciousness is regarded as a phenomenon that could synthesize the essential
aspect of the dissociate process (split personality). Under a neurological
point of view, consciousness is considered a result of a special brain
development with intricate and complex functioning based on features
like connectivity, plasticity, categorization, dynamics of reentry, etc. Beyond
molecules, an intense and permanent electromagnetic field propitiates the
complex brain functioning, its integrity and the unit of its consciousness.
The hypothesis of a disruption of consciousness at energetic level as an
explanation for the schizophrenic phenomenon is presented and discussed.
compare the cerebral regions that are involved in mild and severe negative symptoms, and to determine wither the degree of severity can be
related to specific dysfunctional areas of the brain.The Mildly affected
group showed increase activity in posterior cingulate gyrus, middle frontal
gyrus, precentral gyrus, middle occipital gyrus, cuneus and postcentral
gyrus; and decreased activity in inferior frontal gyrus, orbitofrontal and
fusiform gyrus.The Severe affected group showed increased activity in
globus pallidus, insular cortex,, cuneus, claustrum, post-central and precentral gyrus; and decrease activity in fusyform gyrus and superior temporal gyrus.These results permit correlation of negative symptomatology
with abnormalities in cortico-striato-pallido-thalamic neural circuit.
Severity of negative symptoms is clearly correlated to abnormal left external pallidal activation, evidencing the relevance of this nucleus for cognitive, planning and social capabilities. Specific therapeutic strategies might
be derived from pallidal neurotransmitter systems studies.
S-34
Episode schizophrenia: Implication of research
for clinical practice
S-34-01
Predicting outcome in schizophrenia
Robin Emsley
University of Stellenbosch, Dept. of Psychiatry, Tygerberg, South Africa
P. Oosthuizen
Introduction: Identifying reliable predictors of treatment outcome in
schizophrenia would enable clinicians to recognise patients requiring special interventions at an early stage of the illness. Previous attempts to
identify clinically useful predictors of outcome have been hampered by
methodoligical inconsistencies, including a lack of standardised outcome
measures. Recently proposed operationally defined criteria for remission
provide an opportunity to re-investigate possible predictors of outcome.
The development of operationally defined criteria for remission has
focused attention on improving the overall outcome of schizophrenia.
Studies to date suggest that oral antipsychotics, although very effective in
the short term, do not lead sustained remission in the majority of cases.
Non- and partial adherence appear to be major contributing factors, particularly in the early phases of the illness.
Method: Data will be presented indicating that defining remission
according to sustained symptom reduction is a good way of identifying
people with overall better outcome and quality of life. In another study,
we examined the potential of various demographic, baseline clinical and
early treatment response variables to predict remission and non-remission
in schizophrenia. The remission criteria were applied to a sample of
57 subjects with first-episode psychosis who were treated according to a
fixed protocol over 2 years. We employed discriminant analysis to assess
their ability to predict remission or non-remission. We also assessed the
symptom improvement patterns and compared endpoint psychopathology
in the remitters and non-remitters.
Results: A model incorporating early treatment response, duration of
untreated psychosis, neurological soft signs and depressive symptoms at
baseline was able to correctly predict 82% remitters and 85% non-remitters.
Conclusion: A major shortcoming of oral antipsychotics is their failure to
provide sustained remission in the majority of patients. Alternative methods of antipsychotic delivery need to be urgently sought. A combination of demographic, baseline clinical and early treatment response variables may accurately predict treatment outcome.
S-29-03
Severity of negative symptoms in schizophrenic patients
correlated with abnormalities in cortico-striato-pallidothalamic neural circuit
S-34-02
Cannabis use and gray matter volume in first-episode
schizophrenia: A five-year longitudinal MRI study
Roxana B. Galeno
Directora Instituto, Neurociencias, Mendoza, Argentina
Wiepke Cahn
The Netherlands
Schizophrenia has been characterized as a complex disease, in which various cerebral regions may be affected. The purpose of this study was to
Introduction: Progressive gray matter volume reductions have been

found in schizophrenia and greater decreases seem to be related to poorer
29
outcome. As patients with schizophrenia and cannabis use have a worse

prognosis the progressive gray matter changes in these patients might be
more extensive.
Method: Patients with recent-onset schizophrenia (n=57) and matched
healthy comparison subjects (n=31) were included in this study. For all
subjects magnetic resonance imaging scans were obtained at inclusion
(T0) and after five years (T5).Diagnosis was assessed at T0 and T5 with the
Comprehensive Assessment of Symptoms and History and drug and alcohol use was assessed with the Composite International Diagnostic
Interview. Moreover, drug use was randomly checked with urine toxicology and confirmed by relatives. Patients who fulfilled DSMIV criteria for
alcohol or drug abuse/dependence or had used drugs, other than
cannabis, were excluded from the study (n=6). Of the remaining group,
19 patients used cannabis regularly and 32 patients had not used any
drugs during the five-year follow-up. At T5 clinical and functional outcome were measured and cumulative amount of antipsychotic medication was calculated. At T0 and T5 total brain, gray and white matter, lateral and third ventricle volumes were measured. Percentages of volume
change over time were calculated. Univariate analysis of covariance and
pairwise comparisons were performed.
Results: Cannabis using patients, non-using patients and healthy comparison subjects differed significantly in gray matter, lateral and third ventricle volumes. Cannabis using patients with schizophrenia showed a
more rapid decrease in brain gray matter (F=8.1 df=76 p=.001) and
increase in lateral (F= 3.8 df=76 p=.025) and third ventricle volumes
(F=4.04 df=76 p=.022) as compared to healthy subject and non-using
patients. Gray matter volume decrease occurred in all patients with schizophrenia as compared to healthy subjects, but was significantly greater in
patients using cannabis (Mean Diff.= 2.7 SE=1.1p=.03).Outcome did not
differ between cannabis using and non using patients with schizophrenia.
Conclusion: In schizophrenia progressive gray matter volume decrease
occurs during the first five years of illness. Cannabis use is associated with
a more pronounced decline in gray matter brain volume in patients with
schizophrenia. This decline could be explained by having a comorbid
cannabis abuse/dependence disorder or by the toxic effects of cannabis.
S-34-03
The dynamics of psychopathology in first-episode schizophrenia: 1-year follow-up
Eva Ceskova
Masaryk University, Faculty Hospital Brno, Brno-Bohunice, Czech Republic
R. Prikryl, T. Kasparek
Introduction: The dynamics of psychopathology in first-episode schizophrenia: 1-year follow-upCeskov Eva, Prikryl Radovan, Kasparek
TomasDep. of Psychiatry, Medical Faculty of Masaryk University and
Faculty Hospital Brno, Czech RepublicIntroduction: The early course of
schizophrenia, in particular, is highly variable across patients and is not
generally well characterized in literature. Aim of the study was to examine
in details dynamics of psychopathology in patients with first-episode
schizophrenia and to compare remitters and nonremitters at 1-year
follow-up.
Method: Males hospitalised for the first time with the diagnosis firstepisode schizophrenia who provided informed consent and were
reassessed after one year were included. The psychopathology was evaluated using the Positive and Negative Syndrom Scale (PANSS) before
treatment (on admission), at the end of acute treatment (at discharge)
and at 1-year follow-up .The patients were divided into remitters and
nonremitters when they were reassessed after one year.
Results: 93 patients were examined during the index hospitalisation and
after 1 year. 78% of the patients fulfilled the criteria for remission. In
remitters and nonremitters there was no significant difference in mean
psychopathology and its improvement during the acute treatment. On
admission the most frequently observed symptoms were suspiciousness,
delusions and lack of judgement and insight, at discharge negative and
non-specific symptoms in both remitters and nonremitters. After one year
nonremission was mainly due to negative and general non-specific symptoms. The impaired insight was one of the most frequently observed
symptoms in both remitters and nonremitters at all three time points.
Conclusion: First-episode schizophrenia is characterized by pronounced
acute treatment response which may not be the case in a portion of
30
patients during the further course of the disease from the first psychotic
break down.This confirms the suggestion that the period after the first
psychotic manifestation is a critical one. Impaired insight is very common
phenomenon. Longitudinal prospective studies are needed to verify its
state-related change, and to identify the factors that may underlie the
acquisition of insight.
References: Andreasen, N.C., Carpenter, W.T., Jr., Kane, J.M. et al.:
Remission in schizophrenia: proposed criteria and rationale for consensus.
Am. J. Psychiatry, 162, 2005, pp. 441-449.Granted by MSMT CR
(MSM0021622404)
S-34-04
Social functioning after first episode of psychosis
Livia Vavrusova
University Hospital, Dept. of Psychiatry, Bratislava, Slovak Republic
The likelihood of a good symptomatic and functional outcome has varied
over time and across place. The most likely explanation is that genetic and
environmental factors that influence prognosis vary in a given population
at a given time and thus affect disease outcome in that population. Some
evidence suggests that outcome may have improved with the introduction of antipsychotics. In some studies better outcome is consistently
found in developing compared to developed countries. It has been documented by the WHO International Pilot Study on Schizophrenia. Social-,
cultural-, or biologically based differences between countries or even
regions may significantly affect the severity of schizophrenia and in a certain way also the level of social functioning of schizophrenic patients.
There are several variables of the outcome of psychosis severity of clinical
features, environmental factors (substance use disorders, pre and postnatal factors, etc.), genetic factors, death and disability. Social functioning
(social adaptation) can be measured by various tools - Global Assessment
of Functioning Scale or by the level of employment, or the level of
employment adequate to education of the patient. We present a study on
first episode patients (N=99) treated either with first or second generation
antipsychotics during the period of 12 months after they were discharged
from the hospital. All the patients were assessed regularly (0,3,6,9,
12 month) with PANSS, CGI, GAF and the lever of their employment was
also taken into account.
S-37
First episode psychosis: Integrating neurobiological and psychosocial determinants of outcome
S-37-01
Determinants of outcome in first episode psychosis: An
overview of patient and treatment characteristics
Ashok Malla
Canada
Introduction: Outcome trajectories in psychotic disorders are established
relatively early. Understanding determinants of outcome of First Episode
Psychosis (FEP) is likely to help us in designing interventions which could
improve outcome and influence trajectories of outcome.
Method: In this presentation data will be reviewed from several studies
conducted by the author and colleagues on determinants of clinical and
functional outcome in FEP within the context of specialized treatment of
FEP and potential targets for interventions will be identified.
Results: In a 2 year study of FEP remission of positive symptoms was
achieved by majority of patients (82%) within a mean of ? weeks. Lower
rate of remission was associated with younger age of onset, poor premorbid adjustment, longer duration of psychiatric symptoms (including
non-psychotic) and poor adherence to medication. Time to remission was
associated with poor pre-morbid adjustment and non-adherence to medication. In a larger sample (207) of FEP for patients who achieved remission
(n=161) relapse rate was relatively low (21% and 8.9% in 1st and 2nd
years, respectively). Most patients had achieved good adherence to medi-
cation through an intensive treatment program. Higher risk of relapse was

associated with substance abuse and shorter total duration of untreated
symptoms (including non-psychotic prodromal). Functional outcome in an
independent sample was associated with longer duration of untreated
psychosis (DUP), poor adherence to treatment, higher level of residual
positive and negative symptoms, poor pre-morbid adjustment and poor
performance on working memory. Adherence to medication, longer
untreated illness, substance abuse and, to some extent, cognitive functions were identified as potentially malleable to intervention.
Conclusion: Determinants of these malleable factors would further our
understanding on designing interventions to improve outcome. Factors
associated with poor adherence will be reviewed as an example from an
independent longitudinal sample.
References: Malla, A., Norman, R., Manchanda, R., Townsend,
L. Symptoms, cognition, adherence to treatment and one year outcome
in first episode psychosis, 2002, Psychological Medicine, 2002, 32,
1109-1119. Malla, A., Norman, R., Schmitz, N., Manchanda, R., BechardEvans, L., Takhar, J., Haricharan, R. Predictors of rate and time to remission in first-episode psychosis: a two-year outcome study. Psychol Med.,
2006, 36(5): 649-658. Malla, A; Payne, J. First-episode psychosis: psychopathology, quality of life, and functional outcome. Schizophr Bull,
2005; 31(3): 650-671.
S-37-02
Matcheri Keshavan
USA
S-37-03
Neurocognitive assessment and pharmacotherapy: Towards
prevention of psychosis
Tomiki Sumiyoshi
University of Toyama, School of Medicine, Japan
Yasuhiro Kawasaki, Yuko Higuchi, Mie Matsui, Michio Suzuki,
Masayoshi Kurachi
Introduction: The development of diagnostic tools to identify people vulnerable to psychosis is important from the perspective of improving longterm outcomes by means of effective pharmacotherapy. Several lines of
evidence indicate the possibility that verbal-related cognitive functions,
e.g. verbal learning and memory, as well as electrophysiological measures,
e.g. event-related potentials, provide a clue to early detection of psychosis. According to the neurodevelopmental hypothesis of schizophrenia, psychotropic drugs with neuroprotective effects are expected to facilitate early intervention into the illness.
Method: We evaluated Low Resolution Electromagnetic Tomography
(LORETA) images of P300 in response to auditory stimuli, as well as performance on a comprehensive neuropsychological battery, including a
test of verbal learning memory, in patients with schizophrenia.
Psychopathology and general functional status were also assessed. The
assessment was conducted before and after treatment with perospirone
or olanzapine, newer generation antipsychotics possessing direct or indirect actions at serotonin-5-HT1A receptors. The effect of these antipsychotic drugs on the anatomical distribution of the P300 current source
density was determined.
Results: Treatment with the antipsychotic drugs was associated with
alterations in the configuration of P300 current source density, as demonstrated by LORETA images, in some of the cortical regions thought to be
responsible for the key domains of cognition. For example, patients treated
with olanzapine showed recovery of the left dominant pattern of the
P300 current source density in the temporal regions, which was not evident before treatment. Also, performance on the verbal memory task,
negative symptoms, and quality of life improved in these patients.
Specifically, the degree of recovery of the left-dominant laterality in the
electrophysiological activity was correlated with improvement of verbal
memory performance and amelioration of negative symptoms.
Conclusion: The mechanisms by which the newer generation antipsychotic drugs enhanced verbal learning memory and optimized electrical
brain activity may include neuroprotective actions through modulation of
5-HT1A-mediated neurotransmissions. Since the neurocognitive measures
used in this study have been suggested to represent endophenotypic
aspects of schizophrenia-spectrum disorders, neurocognitive assessment
and pharmacotherapy such as those presented here are likely to contribute

to the detection of people with at risk mental state, and, ultimately,
pave the way towards the prevention of psychosis.
References: Sumiyoshi et al. Am J Psychiatry 158:1722, 2001. Sumiyoshi
et al. Biol Psychiatry 49:861, 2001. Sumiyoshi et al. Prog NeuroPsychopharmacol Biol Psychiatry 30:1299, 2006. Sumiyoshi et al. Int J
Neuropsychopharmacol 9:677, 2006.
S-37-04
Neurocognition, neuroimaging and insight in first episode
psychosis: Common determinants of outcome
Martin Lepage
Brain Imaging Group, Douglas Hospital Research Cent, Verdun, Canada
Introduction: Few clinical or demographic variables can reliably predict
clinical responses in people experiencing a first episode of psychosis (FEP).
The present study explored in a cohort of FEP the heuristic value of neurocognitive functions and functional/structural neuroimaging in predicting short-term clinical response.
Method: Neurocognition was examined in 87 persons presenting with a
first-episode of psychosis and in 25 healthy controls matched on sociodemographical variables. FEP participants were tested as soon as possible
following intake. Six domains of cognition were assessed; verbal memory,
visual memory, working memory, processing speed, problem solving, and
attention. A subgroup of 50 FEP was also scanned on a functional and
structural magnetic resonance imaging protocol. All FEP participants were
assessed on SAPS and SANS at intake and 6 month later. We defined
responders as those FEP participants with global ratings of 2 or less on
SAPS and 3 or less on SANS at 6 month.
Results: These criteria identified 43 FEP participants as responders and 44
as non-responders. Both groups significantly differed in both positive and
negative symptoms at 6 months. They did no differ at intake on their level
of positive symptoms but they did differ however on the severity of negative symptoms with non-responders presenting higher levels of such
symptoms early on. Verbal memory, visual memory, and working memory
clearly distinguished the two FEP groups with responders having better
performance. The imaging results will be presented at the time of the
symposium and preliminary results indicate that the right hippocampal
volume was significantly different between groups.
Conclusion: These findings suggest that relatively high levels of negative
symptoms and poor episodic memory and working memory performance
represent good predictors of short-term clinical response to treatment.
The fact that not all domains of cognitive functions discriminated
between the two FEP groups rules out any explanation pertaining to global neurocognitive functioning. The relation between the specific neurocognitive domains identified in the present study and clinical response
remains to be elucidated but potential suggestions will be presented.
S-38
Immunological mechanisms in pathogenesis
and treatment of schizophrenia and major
depression
S-38-01
Interaction between inflammation and NGF in depression:
Effects by EPA treatment
Cai Song
University of Prince Edwards, Biomedical Sciences, Charlottetown,
Canada
Introduction: Major depression has been associated with an increase in
inflammatory responses, dysfunctions of the HPA axis and neurotransmitter
systems, and with a decrease in the expression or synthesis of neurotrophic
factors. n-3 fatty acid ethyl-eicosapentaenoate (EPA) can effectively treat
depression. Using olfactory bulbectomized (OB) rats, the present study
aimed to determine 1) the interaction between inflammation and nerve
31
growth factors (NGF); and 2) the mechanism by which EPA improves

depression.
Method: Sprague-Dawley rats (280 g) were divided into 4 groups of 10,
and fed control diet (1% palm oil) or 1% EPA for 7 weeks. OB surgery
was performed under ketamine anaesthesia. Following recovery for 4.5
weeks, animal behaviors were tested in an open field. After decapitation; blood and brain samples were collected for measurements of
cytokines, corticosterone, neurotransmitters and mRNA by ELISA, HPLC
and qualitative PCR. The procedure was approved by the Animal Care
Committee. Two-way ANOVA was used for statistics.
Results: Compared to sham operated animals fed palm oil, OB control
rats showed increased concentrations of interleukin (IL)-1 and
prostaglandin (PG) E2, and decreased IL-10, increased activities in the
open field, increased expression of CRF and secretion of corticosterone.
The expression of NGF was significantly decreased in the hippocampus,
while phospholipases (PLA)2 was increased in the hypothalamus. In sham
rats, EPA treatment did not significantly change these parameters.
However, in the OB rats, EPA significantly normalized the hyper-activities
in the open field, reduced CRF and IL-1 expression and corticosterone
secretion, and increased NGF expression. EPA also reduced serum concentrations of PLA2 and PGE2. In several limbic regions, decreased concentrations of noradrenaline (NA), dopamine and serotonin (5-HT), and
increased their turnovers were found in OB controls when compared to
sham controls. EPA treatment attenuated the most changes in the NA and
5-HT systems. Furthermore, anti-NGF treatment blocked EPA effects on
behavior, while celecoxib showed similar effects as EPA.
Conclusion: These results showed, for the first time, the interaction
between inflammation and NGF in a depression model, and demonstrated
that EPA can modulate the inflammation-NTF-neurotransmission network
to benefit depression. (This study was supported by Amarin Neuroscience,
UK, and CIHR, Canada)
S-38-02
The use of anti-inflammatory drugs in schizophrenia and
major depression
Norbert Mller
Ludwig-Maximilians-University, Psychiatry and Psychotherapy, Munich,
Germany
M. Riedel, M. J. Schwarz
COX-2 inhibition seems to balance the type-1/type-2 immune response,
possibly via inhibition of prostaglandin E2 inhibition and COX-2 inhibition
reduces proinflammatory cytokines. Moreover, COX-2 inhibition has an
impact to the glutamatergic neurotransmission and influences the tryptophan/kynurenine metabolism: all three components seem to be involved
in the pathophysiology of psychiatric disorders, particularly in schizophrenia and major depression. Therefore, we performed at first a prospective,
randomized, double-blind study of therapy with the COX-2 inhibitor celecoxib add-on to risperidone in acute exacerbation of schizophrenia A
therapeutic effect of celecoxib was observed. Immunologically, an
increase of the type-1 immune response was found in the celecoxib treatment group. The clinical effect of COX-2 inhibition was especially pronounced regarding cognition in schizophrenia. The finding of a clinical
advantage of COX-2 inhibition, however, could not be replicated in a
second study. Further analysis of the data revealed that the outcome
depends on the duration of the disease. The efficacy of therapy with a
COX-2 inhibitor seems most pronounced in the first years of the schizophrenic disease process. This observation is in accordance with results
from animal studies.Due to the increase of proinflammatory cytokines
and PGE2 in depressed patients, antiinflammatory treatment would be
expected to show antidepressant effects also in depressed patients.
Accordingly, a clinical antidepressant effect of rofecoxib was found in
patients with osteoarthritis. An own randomized double blind pilot addon study using the selective COX-2 inhibitor celecoxib in MD showed a
significant therapeutic effect of the COX-2 inhibitor on depressive symptoms. Although those preliminary data have to be interpreted cautiously
and intense research has to be provided in order to evaluate further the
therapeutic effects of COX-2 inhibitors in MD, those results are encouraging for further studies. dealing with the inflammatory hypothesis of
depression with regard to pathogenesis, course and therapy.It has to be
considered, however, that therapy with COX-2 inhibitors is currently
32
under discussion - as therapy with other non-steroidal antiphlogistics due to cardiovascular side-effects. Regarding the possible role of inflammation in schizophrenia, depression and possibly other psychiatric disorders, anti-inflammatory therapy should be taken into the focus of further
research.
S-38-03
Infectious agents and schizophrenia and bipolar disorder
Robert H. Yolken
Johns Hopkins School of Med., Stanley Laboratory, Baltimore, MD, USA
Schizophrenia and bipolar disorder are complex neuropsychiatric disorders with multiple etiologies related to both genetic and environmental
factors. Epidemiological studies indicate that exposure to infectious
agents are one of the environmental factors which contribute to disease
eiopathogenesis. Our laboratory has been working establishing the relationship between infectious agents and risk of schizophrenia and bipolar
disorder. Findings to date indicate that serological evidence of infection
with common infectious agents such as Toxoplasma gondii and human
herpesviruses can increase the risk of these disorders in many individuals.
Furthermore genes which contribute to the host response to these agents
can also contribute to the disease risk for schizophrenia and bipolar disorder. Trials are ongoing to determine if pharmacological methods which
affect the replication of Toxoplasma gondii and herpesviruses can alter
the clinical course of these disorders. The successful conclusion of these
trials may lead to new methods for the prevention and treatment of
human brain diseases.
S-38-04
Involvement of the immune system and the kynurenine
metabolism in pathophysiology and treatment of schizophrenia
Markus J. Schwarz
University of Munich, Depart of Psychiatry, Germany
Michael Riedel, Norbert Mller
Introduction: A large body of evidence points to the involvement of an
immune process in the pathophysiology of schizophrenia. Although there
is a controversial discussion regarding the type of immune activation (Th1
dominant / autoimmune as in rheumatoid arthritis versus Th2 dominant /
allergy-like), a mild chronic immune process in the CNS may anyway be
related to the repeatedly reported progressive reduction of brain volume
in schizophrenia. Recent data indicate that the endogenous NMDA receptor antagonist kynurenic acid may induce schizophrenia. Kynurenic acid is
mainly produced by activated astrocytes (immunologically important glia
cells, responsible for a Th2-like immune response in the CNS). COX-2
inhibitors such as celecoxib are known to inhibit the synthesis of
kynurenic acid and to alter the type of immune activation.
Method: We have performed several studies on the immune system, one
study on the relationship between kynurenic acid and the astroglial marker
S100B in the CSF, as well as two placebo controlled clinical studies using
the COX-2 inhibitor celecoxib as an add-on treatment in schizophrenia.
Results: Our data strongly indicate a predominance of the Th2 system of
the specific immune system, while additionally the monocytic system
seems to be also markedly activated. We found a strong relationship
between kynurenines and S100B in CSF. Finally, our clinical study demonstrated good therapeutic efficacy in schizophrenic patients during early
stages of the disease.
Conclusion: Our data underline the observations of active immune
process in schizophrenia and indicate a functional relationship between
the kynurenine pathway intermediates and astroglial function. Previous
studies of schizophrenia have demonstrated a significant elevation of
KYNA in postmortem pre-frontal cortex and in CSF. These may be related
to altered astrocytic function. Manipulation of both, the immune
response and the kynurenic acid synthesis showed therapeutic afficacy.
These data indicate that immune dysfunction in schizophrenia is not just
an epiphenomenon, but may be directly related to the pathomechanism
of the disorder.
S-42
New advances in schizophrenia
S-42-01
How to improve compliance in schizophrenia treatment
Franck Bayle
Paris, France
Poor compliance remains one of the major issues in prescribing antipsychotic in particular, and in medical everyday practice in general.
Therapeutic non-compliance of patients with schizophrenia is real problem due its frequency (approximately one out of two patients concerned) as well as its individual and collective consequences (morbidity-mortality, economic cost. Recently the CATIE study show that after 18 months
of treatment, almost 30% of patient were not taking their treatment
despite their willingness in participate in a double blind study and the fact
that they were getting treatment at no cost. Low compliance is related
with relapse and poor outcome. Many factors are linked with compliance
in which two are more salient insight, drug addiction. In fact those factors
should be classified as linked to the patient, linked to the treatment and
linked to the therapeutic relationship. This last point is deserved by the
lack of study measuring is loading. Keeping in mind the impact of psycho
education, one could ask how much the relationship established between
patient and doctor could interfere with compliance. We report the development and first psychometric data on a new scale specially built to
measure the therapeutic alliance in psychiatric day-to-day practice, the
4PAS. Exploratory factor analysis of the alliance scale produced two main
factors. The first and strongest factor, Factor I, reflects, empathy experienced and Factor II seems related to Psycho education. Those results
are discussed with the aim to provide help about one of the cornerstone
in which the improving compliance process could be set.
S-42-02
Metabolic disturbances in schizophrenia, treatment effects
J. Peuskens
Kortenberg, Belgium
Marc De Hert
Metabolic abnormalities have consistently been identified as a part of
schizophrenic illness, but with the introduction of second-generation
antipsychotics and their possible association with metabolic abnormalities, the interest in this topic has been renewed. Many studies have now
provided convincing evidence for a high risk of obesity, diabetes and
other glucose abnormalities, the metabolic syndrome, and mortality due
to elevated cardiovascular risk in patients with schizophrenia. These metabolic abnormalities are of major clinical concern, not only because of their
direct, somatic effects on morbidity and mortality, but also because of
their association with psychiatric outcome, such as a higher prevalence of
psychotic and depressive symptoms, a lower functional outcome, a worse
perceived physical health and lower adherence to medication. The reasons that underlie the high prevalence of these metabolic abnormalities
are much debated, especially when considering the possible role of
second-generation, atypical antipsychotics in the occurrence of these
abnormalities. Many studies have suggested a role of (certain) atypical
antipsychotics in the occurrence of metabolic abnormalities; case reports,
cross-sectional or retrospective studies and prospective studies. Different
consensus groups have proposed guidelines for screening, monitoring
and management of metabolic abnormalities for people treated with
antipsychotic agents.
S-42-03
How to use pharmacogenetics in schizophrenia treatment
areas of research in molecular medicine Efforts to identify these factors

have been based on association studies focusing on genes encoding
enzymes involved in drug metabolism or on genes encoding proteins
involved in the dopaminergic and serotoninergic systems targeted by
antipsychotic agents In addition, most of the studies performed to date
do not conform to the only guidelines yet published for pharmacogenetic
studies of antipsychotics Most of the association studies carried out on
antipsychotic drug response have focused on clozapine, an atypical
antipsychotic agent with a unique efficacy in otherwise non-responding
patients. None of these previous studies investigated the involvement of
norepinephrinergic system genes in drug response in schizophrenia despite
increasing evidence that this neurotransmitter plays a role in schizophrenia. Neurobiological, psychopharmacological and biochemical findings
indicate that noradrenergic dysfunction plays an important role in the
pathogenesis of schizophrenia. In particular, hyper- and hypoactivity of
the central norepinephrine system seem to be involved in the pathogenesis of positive and negative symptoms. Furthermore, the norepinephrine
transporter (NET) seems to be inhibited by antipsychotic drugs such as
olanzapine, risperidone and clozapine
Method: We prospectively assessed short-term drug response in
75 Caucasian schizophrenic patients from Western Europe treated with
olanzapine (n = 43) or risperidone (n = 32), using the Positive and
Negative Syndrome Scale. We then assessed the association between two
SLC6A2 gene polymorphisms (T-182C and G1287A) and drug response in
this sample.
Results: The improvement in PANSS positive subscore was significantly
greater in patients homozygous for the A1287 allele than in other
patients, and significantly smaller in patients homozygous for the C-182
allele than in other patients.
Conclusion: Our results suggest that these polymorphisms are specifically
involved in the variation of positive symptoms in schizophrenic patients.
S-42-04
Immunological and inflammatory aspects in schizophrenia
Norbert Mller
Ludwig-Maximilians-University, Psychiatry and Psychotherapy, Munich,
Germany
Markus J. Schwarz
Introduction: The role of infection and inflammation in the aetiology of
schizophrenia has gained more attention during the last years. A persistent (chronic) infection as aetiological factor in schizophrenia is discussed
since many years. Signs of inflammation were observed in schizophrenic
brains and the term mild localized chronic encephaltis was proposed.
Results of epidemiological studies showed that infection of the CNS in
childhood increases the risk of becoming psychotic later on five-fold.
Results: Recent research points out that not one single pathogen but the
immune response of the mother is related to the increased risk for schizophrenia. Several reports described increased serum IL-6 levels in schizophrenia. IL-6 is a product of activated monocytes and of the activation of
the type-2 immune response. Moreover, several other signs of activation
of the type-2 immune response are described in schizophrenia, while the
type-1 immune response is decreased in the majority of schizophrenic
patients. These two types of immune responses are strongly interacting
with the tryptophan/kynurenine metabolism leading to an accumulation
of kynurenine acid, which is an endogenous NMDA receptor antagonist.
Several studies point out that NMDA receptor antagonism plays an important role in the pathogenesis of schizophrenia.
Conclusion: Anti-inflammatory medication, in particular cyclo-oxygenase2 inhibitors, balances the type-1 and type-2 immune response. Therefore
anti-inflammatory medication was hypothesized to have therapeutic
effects in schizophrenia, in the meanwhile two studies showed antipsychotic effects of COX-2 inhibitors in early stages of schizophrenia.
Regarding the role of the inflammatory process in schizophrenia, antiinflammatory therapy should be taken into the focus of further research.
Pierre Michel Llorca

Clermont Ferrand, Belgium
Introduction: The identification of genetic factors underlying individual
differences in response to antipsychotic agents is thus highly promising
33
BRAIN FUNCTION - Symposia
S-31
Heart and brain. A whole new era
T8 Brain Function
S-31-01
Stress, coronary disease and cortial hyperactivation
Francisco Klein
There has been a steady increase in the amount of data that suggest that
cerebral cortical hyperactivation in relation to stressful environmental stimuli or experimental mental challenges show a somewhat predictable
pattern. Moreover, it has also been shown that this pattern is different
when normal individuals are compared to those developing stress induced myocardial ischemia. The physiologic mechanisms that integrate the
cognitive process to the somatic responses include the autonomous nervous system (both adrenergic and parasympathic), the adrenal medulla,
the hypothalamus-hypophyseal axis, the Renin-Angiotensin-Aldosterone
system and Vasopressin secretion, among others. The neural pathways of
the emotional stimuli involve the prefrontal cortex, the limbic system, and
specific areas of functional activation related to the particular kind of
acting stimuli. The prefrontal cortex has an important role in the cognitive processing of the stimuli. The limbic system, through the hypothalamus, play an integratory function in order to exert control on the biological functions. At the Hippocampus these stimuli are integrated into their
particular contextual frame, while the integration into an eventual emotion of fear depends on the Amygdala . Connections from the cingulate
gyrus contribute to recognition and awareness of the emotions involved.
There is evidence that cerebral cortical hyperactivation involve a particular pattern of selective activation of the angular and cingular gyri, of the
visual cortex, the fusiform gyrus and the cerebellum. At the same time,
other areas like the right parietal cortex, the thalamus, the superior frontal and the middle temporal gyrus show marked hypoactivation. There is
evidence that these normal patterns show a marked increase in
patients that develop stress induced myocardial ischemia (SIMI). There has
also been shown that the hemodynamic response to stressful stimuli in
patients with SIMI is different to that developed by patients with exercise
induced myocardial ischemia (EIMI). In the first case, the increase in peripheral vascular resistance is the main patophysiologic finding while the
insufficient increase in the cardiac index to meet the cardiovascular
demands is the mechanism involved in EIMI. There is not universal agreement over which should be the standard methods to screen for SIMI.
Electrocardiogram, Ultrasound, Radioisotopes, MRI and Angiograms all
have been used in experimental studies but there is not consensus either
on their specificity and/or sensitivity. There are also considerable controversies over which should be the recommended experimental mental
challenge for the screening process. There is an increasing interest in the
pharmacologic or non pharmacological interventions that would eventually modulate these responses.
S-31-02
Facundo Manes
S-31-03
Depression, anxiety and morbi-mortality in heart disease
Marcelo Cetkovich-Bakmas
Introduction: Depression is present in 20% of outpatients with coronary
heart disease and in 30% of patients with congestive heart failure.
Evidence linking depression and cardiovascular diseases shows that that
the association is not random, but driven by depression as a risk factor.
Method: Latest findings in the field will be reviewed
Conclusion: Within the Heart & Soul study project Ruo et al (demonstrated an association between depressive symptoms and lower exercise
capacity in the treadmill, in an independent way of heart function. On
the other hand they found that depression lowers patients health self per-
34
ception, symptom burden, physical limitation and quality of life. Anger

has been reported not only as a risk factor for AMI in older men, but also
as an acute trigger of the onset of an acute myocardial infarction, with
the highest risk within two hours after the anger outburst. On the other
hand, other study showed that moderate levels of anger could have a
protective effect against AMI.
References: 1. Glassman, A. H., V. L. Serebruany, et al. (2002).
Sertraline Tratment of major depression in patients with acute MI or
unstable angina. JAMA 288: 701-709. 2. Kawachi I, Sparrow D, Spiro A,
Vokonas P, Weiss ST (1996). A prospective study of anger and coronary
heart disease. The Normative Aging Study. Circulation, 94(9): 2090-5 3.
Mittleman MA, MacLure M, Sherwood JB, Mulry RP, Tofler GH, Jacobs SC,
Friedman R, Benson H, Muller JE. (1995) Triggering of acute myocardial
infarction onset by episodes of anger. Determinants of the Myocardial
Infarction Onset Study Investigators. Circulation, 92(7):1720-5. 4. Ruo,
B., J. S. Rumsfeld, et al. (2003). Depressive Symptoms and HealthRelated Quality of Life. JAMA 290(2): 215-221. 5. Ruo, B., J. S. Rumsfeld, et al. (2004). Relation between Depressive Symptoms and Treadmill
Exercise Capacity in the Heart and Soul Study. Am J. Cardiology 94: 9699. 6. Vieweg, W. V., D. A. Julius, et al. (2006). Treatment of Depression
in Patients with Coronary Heart Disease. American Journal of Medicine
119: 567-573. 7. Whooley, M. A. (2006). Depression and Cardiovascular
Disease. Healing the Broken Heart. JAMA 295(24): 2874-2881. 8.
Zellwegger, M. J., R. H. Osterwalder, et al. (2004). Coronary Artery
Disease and Depression. European Heart Journal 25: 3-9.
S-31-04
Depression and cardiovascular disease: Possible impact of
thyroid function and thyroid immunity
Robertas Bunevicius
Institute of Psychophysiology, Palanga, Lithuania
Introduction: Despite increasing information about links between
depression and cardiovascular function, some potentially important factors, such as dysfunction of the thyroid axis and thyroid immunity have
only begun to be studied. In this report we will present our data on possible involvement of thyroid gland in presentation of affective disorders in
primary care patients and in cardiac patients.
Method: Patients were screened for symptoms of depression and for
symptoms of anxiety using the Hospital Anxiety and Depression Scale
(HADS), were evaluated for thyroid immunity by the ultrasonographic
imagining of the thyroid gland, and were evaluated for thyroid function
by assessing concentration of thyroid axis hormones.
Results: In primary care setting among patients with hypo-echoic thyroid,
that indicates autoimmune process in the thyroid gland, prevailed
women, those patients were older, had higher body mass index and had
higher blood pressure in comparison to patients with normo-echoic thyroid. Women, but not men, with hypo-echoic thyroid had higher scores
on the anxiety subscale of the HADS (p=0.03).Among women with hypoechoic thyroid, only those pre-menopause, but not those post-menopause
had greater prevalence of high scores on the depression subscale of the
HADS (p=0.02) and greater prevalence of using psychiatric medications
(p=0.001) in comparison to women with normo-echoic thyroid. In cardiac
setting patients with depressive symptoms had lower free triiodothyronine
concentrations (p=0.04) in comparison to cardiac patients without
depressive symptoms. They also showed a strong trend (p=0.058)
towards a higher incidence of the low T3 syndrome. Symptoms of anxiety
had no impact on thyroid hormone concentrations.
Conclusion: Results of this study demonstrate that thyroid immunity is
related to mood symptoms as well as to higher body mass index and
higher blood pressure in primary care patients. In cardiac patients symptoms of depression are associated with decrease in triiodothyronine concentration.
References: R Bunevicius, G Varoneckas, AJ Prange Jr, V Gintauskiene,
AL Hinderliter, SS Girdler. Depression and thyroid axis function in coronary
artery disease: impact of cardiac impairment and gender. Clin Cardiol
2006; 29: 170-174. R Bunevicius, J Peceliuniene, N Mickuviene, A
Bunevicius, VJ Pop, SS Girdler. Thyroid immunity assessed by ultrasonographic imaging and mood of patients in primary health care. J Affect
Disorders 2006 (in press).
S-35
The emotional brain: Function and dysfunction
in psychiatric disorders
T8 Brain Function
S-35-01
Emotional memory and schizophrenia: Behavioral and
functional neuroimaging findings
Martin Lepage
Brain Imaging Group, Douglas Hospital Research Cent, Verdun, Canada
Introduction: Schizophrenia is characterized by significant problems pertaining to emotional regulation. For instance, flat or blunted affect, anhedonia and inappropriate displays of emotion often typify the clinical presentation and their persistence is associated with poor clinical and functional outcome. However, little is known about how those emotional dysfunctions impact on cognitive processing in general and on episodic
memory processing in particular.
Method: In a series of behavioral and functional Magnetic Resonance
Imaging (fMRI) studies, we explored the impact of emotional information
on memory performance and neural activity. In the main fMRI study, we
examined the effects of emotional expression for faces (sad, happy, or
neutral) in a group of 30 patients with schizophrenia and 24 controls
during a memory encoding and recognition task.
Results: Emotional expression had the same modulatory influence on
memory performance in both groups. At the brain level during emotional
memory encoding, decreased activity in insula bilaterally and right amygdala was observed in the schizophrenia group relative to the control
group. In another behavioral study we explored emotional memory for
faces but this time examined fearful faces along with happy and neutral
ones. Both groups performed similarly on a recognition memory test for
happy and neutral faces but the schizophrenia group had lower performance for fearful faces relative to the control group.
Conclusion: These behavioral findings suggest a normal modulation of
memory by emotions in people with schizophrenia except for fearful
expressions. The fMRI results suggest a diminished limbic response in
people with schizophrenia during emotional memory processing.
S-35-02
Executive and emotional deficits in patients with ADHD
Facundo Manes
Institute of Cognitive Neurology (INECO), Institute of Neurosciences Favaloro Fundation, Buenos Aires, Argentina.
Introduction: A prevailing theory of mechanisms underlying idiopathic
ADHD is that the disorder reflects principally a dysregulation of executive
functions. In recent years, researchers have investigated the cognitive profile of ADHD in adults using several neuropsychological instruments.
However, no clear pathognomonic profile for this condition has emerged.
Our objective was to detect specific executive and emotional decisionmaking deficits in adult ADHD patients
Method: Twenty four unmedicated adult ADHD patients (DSM-IV criteria) and twelve normal controls underwent a standard neuropsychological
examination followed by an executive battery that included: Theory of
Mind tasks, the Hotel Task, the Met-hv and the Iowa Gambling task (IGT).
The Iowa Gambling Task aims to characterize abnormalities in social and
emotional decision-making using a standardized laboratory procedure.
Results: All ADHD patients had standard cognitive tests within normal
ranges. Significant differences were found between ADHD and normal
controls in: a) Theory of Mind tasks (p<0.001), b) number of tasks
attempted (p=0.01) and total deviation from optimal time allocation
(p=0.003) in the Hotel Task, c) total error score (p<0.001), number of
broken rules (p=0.002) and failures of interpretation (p=0.008) in the
Met-hv, and d) in the IGT task (p<0.0001).
Conclusion: These results showed that this battery is sensitive enough to
detect executive and emotional decision-making dysfunction in a group
of adult ADHD patients, suggesting that executive deficits mediated by
circuitry encompassing the frontal lobes are core symptoms in adult
ADHD patients.
S-35-03
Influence of anxiety on the neural responses to emotional
stimuli
Jorge Armony
McGill University, Douglas Hosp. Research Centre, Montreal, Canada
In this talk I discuss the neural networks involved in the processing of
emotional stimuli, especially those related to threat. In particular, I will
focus on how these responses are modulated by anxiety and other individual differences factors. I will also discuss how emotional stimuli can
influence memory. Behavioral results, as well as data from functional
magnetic resonance imaging (fMRI) conducted with healthy participants
and individuals suffering from PTSD will be presented.
S-35-04
Structural and functional changes in the brain of depressed
individuals
Philippe Fossati
CNRS UMR 7593, Psychiatry, Paris, France
Introduction: Neuroimaging has assumed a unique position in defining
the anatomy of depression. The main goal of this talk is to discuss an
overview of the structural and functional brain imaging literature on
depression.
Results: The main modifications demonstrated by structural magnetic
resonance imaging (MRI) are a reduction in the gray matter volume within
the prefrontal cortex, the hippocampus, and the striatum. Studies of cerebral blood flow and glucose metabolism in primary depression have consistently revealed that depression is a system-level disorder affecting discrete but functionally integrated cortical, subcortical, and limbic pathways. Measures of brain metabolism or regional blood flow at baseline
(resting state studies) have involved ventral and dorsal prefrontal cortex,
anterior cingulate, basal ganglia, amygdala and hippocampal regions.
Changes in specific neural network have also been associated with symptomatic dimensions of depression. Dorsolateral prefrontal activity has
been linked to psychomotor speed and executive functions; parietal and
parahippocampus with anxiety; medial frontal and cingulate with cognitive performance and emotional bias. Studies of resting state patterns are
complemented by studies of antidepressant treatment and parallel functional activation experiments with PET scans or functional MRI examining
specific cognitive, motor and affective processes in healthy volunteers or
depressed patients. Depression involves a bias of cognitive processing
toward negative emotional information congruent with the mood of the
depressed patient. This emotional bias could reflect impaired modulation
of brain response to negative stimuli.The medial prefrontal cortex (MPFC)
may mediate the emotional bias in depression. We recently demonstrated
than self-related processing of emotional words induces a unique activation in the dorsal MPFC whereas processing of emotional words in general terms induced activation in more lateral prefrontal areas (Fossati et al,
2003). Preliminary results of a study using self-referential task in
depressed patients showed impaired modulation of the MPFC suggesting
than depression may disrupt self-monitoring of emotional stimuli, especially negative stimuli.
Conclusion: Taken together these findings suggest that depression may
be associated with impairment of structural and functional plasticity and
cellular resilience within a specific cortico-limbic neuronal network. These
findings also suggest that the recurrence of depressive episodes may
enhance the deleterious effect of depression on structural and functional
plasticity of these circuits, the so-called neurotoxic hypothesis of
depression.
35
S-41
Advances in brain stimulation treatments in
psychiatry
T8 Brain Function
S-41-01
Repetitive Transcranial Magnetic Stimulation in a clinical
setting. Customising parameters to the patients clinical
status. From unilateral to bilateral stimulation
Alexander G. Lyford-Pike
Instituto de Psiquiatria y Psicologia de Montevideo, Montevideo (I.P.M.),
Uruguay
E. Galeano, B. Quadrelli, S. Olivera
Introduction: To demonstrate the effectiveness and safety of repetitive
Transcranial Magnetic Stimulation (rTMS) treatment in patients with
affective disorders. Two groups with depressive episodes, according to
DSM-IV, were compared. Bilateral or unilateral stimulation of the frontal
lobes was applied.
Method: The first group (38 patients) received unilateral stimulation, and
the second (20 patients) received bilateral stimulation. Exclusion criteria
were epilepsy, cardiac pacemaker, alcoholism, drug abuse, brain trauma,
neurologic diseases, patients aged over 75. Both groups included patients
with and without antidepressive medication; fixed doses were maintained. A rapid rate Magstim Rapid stimulator was used. Effectiveness
was assessed on the basis of pre and post treatment Beck and Hamilton
scales, and 50% decrease with respect to baseline was considered as
improvement criterion. Patients signed written consent.
Results: Although the results obtained are not statistically significant due
to the size of the sample, a descriptive approach shall be made. Sixtyseven per cent (Beck) and 61% (Hamilton) of the patients improved their
respective scores in the first group. The results in the second group were
70% (Beck) and 85% (Hamilton), respectively. Relapse rates were 54%
and 33% of all patients, respectively.
Conclusion: rTMS is a safe and effective option for treating depressive
disorders. A larger number of patients responded to bilateral than to unilateral stimulation. More patients relapsed in the second group compared
to the first.
S-41-02
Vagus nerve stimulation - the hearts and the guts of the
matter
Michael Trimble
Institute of Neurology, London, United Kingdom
Amongst the newer treatments for depression and mood instability is
Vagus Nerve Stimulation (VNS). As experience is gathered it seems that
VNS is not a classical antidepressant, and patients who are most appropriately assigned VNS treatment have treatment resistant depression, an
entity which is recognised but rather poorly defined. The presentation will
note the extensive data on the use of VNS in epilepsy which led to observations of improvements of mood in that population. Thus, VNS may be
seen as another example of a therapy which appears anticonvulsant, but
also beneficial to patients with mood disorders. Data will then be presented
from the completed trials of VNS in patients with treatment resistant
depression. Some interesting features with regards to response will be
noted, in particular the increase in the number of responders and remitters over a 12 month period. Thus, greater improvements are noted at
12 months in comparison with 3 months. The presentation will then consider why stimulation of the Vagus Nerve may be of importance for
mood. This is discussed in the context of presenting information on
patients with VNS implants who have been studied using fMRI while
carrying out memory tasks comparing performance during stimulation
with no stimulation. The data suggest that stimulation interferes with
memory for negative emotional stimuli. The importance of the vagus
nerve for feeling good, for having a good heart and satisfied guts will be
remarked upon and a neurovegetative hypothesis of VNS function in
mood disorders will be discussed.
36
S-41-03
Commonalities of use parameters in brain stimulation and
basic underlying principles
Mark George
502 N, Charleston, USA
Introduction: While there has been much interest in the newly emerging
brain stimulation techniques as potential treatments, there has been inadequate attention paid to the basic commonalities across the methods. All
methods share in common the production of electricity in some form,
applied to nervous tissue either directly (e.g deep brain stimulation) or
indirectly (e.g. transcranial magnetic stimulation).
Method: In this lecture we will overview this field from the actual physical properties of the electricity used, and compare techniques from the
point of view of a neuron and the electrical stimulation it receives.
Conclusion: It is important as the field of brain stimulation advances, to
understand more thoroughly the fundamental properties of the techniques, and how these change neuronal function. With this basic understanding, one can then begin to rationally choose different methods for
different intended behavioral or therapeutic effects, and modify current
techniques to more efficiently interact with brain.
References: 1.George MS, Belmaker RH. TMS in Clinical Psychiatry
(American Psychiatric Press, Washington, DC, 2006). 2. Wei XF, Grill WM.
Current density distributions, field distributions and impedance analysis of
segmented deep brain stimulation electrodes. Journal of Neural
Engineering, 2(4), 139-147 (2005). 3. McIntyre CC, Grill WM, Sherman
DL, Thakor NV. Cellular effects of deep brain stimulation: model-based
analysis of activation and inhibition. Journal of Neurophysiology, 91(4),
1457-1469 (2004). 4. Grill WM, Jr. Modeling the effects of electric fields
on nerve fibers: influence of tissue electrical properties.
IEEE.Trans.Biomed.Eng., 46, 918-928. (1999).
GENETICS - Symposia
S-05
Endophenotypes and molecular genetics of
major psychoses
T9 Genetics
S-05-01
Abnormal cortical functioning in obligate carriers of
schizophrenia
Tonmoy Sharma
The Cognition Group, The Topkis Building, Suite 100, Newark, DE,
United Kingdom
Introduction: Numerous cognitive functions sub-served by anatomically
and functionally interconnected networks of specialized brain regions are
found to be disturbed in schizophrenia. One particularly well studied
function is that of working memory where a network of parietal and
frontal areas has been shown to have a different pattern of activation in
normal subjects and patients with schizophrenia. We have investigated
working memory networks in presumed obligate carriers of a psychotic illness using functional magnetic resonance imaging (fMRI).
Method: Eight presumed obligate carriers of a schizophrenia were compared to eight age and sex-matched healthy subjects. T2* weighted gradient-echo echoplanar MR images depicting blood oxygen level-dependant (BOLD)-contrast were acquired using a 1.5 Tesla scanner from
14 near-axial slices parallel to the intercommissural line. Behavioural data
in terms of response latency and accuracy were acquired (via button presses)
from all subjects during the scanning. The fMRI data were analysed, for
task and group effects, using statistical parametric mapping software
(SPM99).
Results: There were no significant differences between presumed obligate carriers and normal comparison subjects for behavioural measures.
A network of parietal and frontal areas was activated in both groups, but
there was evidence for a reduced response in obligate carriers, as compared to control subjects, in the anterior cingulate, dorsolateral prefrontal
cortex and right cerebellum. Relative to comparison subjects, presumed
obligate carriers also showed lack of correlated activity between (a) anterior cingulate and frontal regions and (b) cerebellum and frontal regions
Conclusion: Presumed obligate carriers of schizophrenia exhibit subtle
differences in brain functions, specifically in frontal and cerebellar functioning. These abnormalities may represent important biological marker
(an endophenotype) for the transmission of the schizophrenia genotype.
References: Honey GD, Bullmore ET, Soni W, Varatheesan M, Williams
SCR, Sharma T (1999) Differences in frontal cortical activation by a working memory task following substitution of risperidone for typical antipsychotic drugs in patients with schizophrenia. Proc Nat Acad Sci, 96(23),
13432-13437 Sharma, T, Lancaster, E, Lee, D, Lewis, S, Sigmundsson, T,
Takei, N, Gurling, H, Barta, P, Pearlson, G and Murray, R (1998) Brain
Changes in Schizophrenia. A volumetric MRI study of families affected
with schizophrenia - The Maudsley Family Study 5. Br J Psychiatry, 173,
132-138.
S-05-02
Linkage of pCREB in families of bipolar probands
Martin Alda
Canada
Gustavo X. Turecki, Xiujun Sun, Jun-Feng Wang, Tomas Hajek, Catalina
Lopez de Lara, Anne C. Duffy, Paul Grof, Guy A. Rouleau, L. Trevor
Young
lation.
Method: We conducted full genome scan of BD families with 811 DNA
markers. The clinical sample consisted of 36 kindreds with 282 genotyped
subjects (135 affected with BD or recurrent depression according to both
RDC and DSM-IV criteria). All probands were responders to lithium
monotherapy; the prevalence of non-affective psychiatric disorders (such
as schizophrenia, anxiety, or substance abuse) in these families was at the
general-population level. Basal and forskolin stimulated pCREB levels
were measured in transformed lymphoblasts using immunoblotting; data
were available in eleven families (44 subjects).
Results: Using the clinically defined phenotype we found a suggestive
evidence of linkage in 3p, 6p, 14q, 17q, and 21q regions, but not in 8p,
13q, 22q, or 18q reported by others in samples of BD patients with
prominent psychosis, or with comorbid panic disorder and/or rapid mood
switching (2). Affected as well as unaffected family members showed elevated basal pCREB levels and blunted response to forskolin compared to
healthy controls. Both basal and stimulated levels appear heritable (intrafamily correlations of ~0.7). Analyzing the biochemical phenotype we
obtained moderate evidence of linkage in some of the same chromosomal regions as when using the clinical phenotype (3p, 14q, 17q) as well
as in additional regions (2p, 19q, 22q).
Conclusion: Clinically defined subtypes of BD appear to be linked to distinct chromosomal regions. pCREB levels may represent an endophenotype that could provide a useful lead in search for BD susceptibility genes.
References: 1. Gottesman II and Gould TD. The endophenotype concept
in psychiatry: etymology and strategic intentions. Am J Psychiatry 2003;
160: 636-645. 2. MacQueen GM et al. The phenotypes of bipolar disorder: relevance for genetic investigations. Mol Psychiatry 2005; 10: 811826.
S-05-03
Neurophysiologocal endophenotype and nicotinic alpha 7
receptor in schizophrenia
Ann Olincy
Univ. Colorado Health Sciences, Dept. of Psychiatry, Denver, CO, USA
Lynn L. Johnson, Jamey Ellis, Alexis Ritvo, Jeff Hollis, Robert Freedman
Evidence of nicotinic involvement in schizophrenia began with the observation that people with schizophrenia are heavy smokers. Post-mortem
studies have shown decreased numbers of both high affinity and low
affinity nicotinic receptors in the hippocampi of people with schizophrenia.
The P50 auditory evoked potential is a neurophysiological endophenotype that, in people with schizophrenia, demonstrates the inability to
inhibit the response to the second of two identical auditory stimuli 500
milliseconds apart. This deficit corrects with the administration of high
dose nicotine. The P50 auditory evoked potential is inherited in an autosomal co-dominant manner with one of the parents and one half of the
siblings also having the abnormality. Genetic linkage in large pedigrees
with schizophrenic probands shows that a specific gene product, the a7
nicotinic receptor, is responsible for failure to inhibit the P50 cerebral
evoked response to repeated stimuli. These pedigrees also showed weaker
linkage of the a7 nicotinic receptor to schizophrenia. The gene for the
alpha-7 low affinity nicotinic receptor is located on chromosome 15q14.
Linkage of the P50 auditory evoked potential deficit is associated with
marker D15S1360 with a Lod score of 5.3. Candidate gene analysis suggests that schizophrenic patients are more likely to carry promotor polymorphisms and these polymorphisms may contribute to P50 deficits.
There are several studies that are using the P50 auditory evoked potential
as an endophenotype to replicate this genetic finding and to try to discover interactions between genes.
Introduction: A growing consensus indicates that genetic mapping studies in psychiatry are complicated by problems in phenotype definition.
Intermediate phenotypes (endophenotypes) have been suggested as a
way to obtain quantifiable and more reliable phenotypic measures (1). In
this paper we will compare results of genome scans in bipolar disorder
(BD) obtained with different phenotypic variables. As an endophenotype
we used levels of basal and forskolin stimulated pCREB, based on our earlier findings. In particular, we showed that patients with BD had increased
basal levels and decreased (or rather absent) response to forskolin stimu-
37
GENETICS - Symposia
S-05-04
Performance on WCST in relation to polymorphisms of
various genes in schizophrenia and bipolar illness
Janusz Rybakowski
Poland
Alina Borkowska, Maria Skibinska, Monika Dmitrzak-Weglarz, Joanna
Hauser
Introduction: The performance on the Wisconsin Card Sorting Test
(WCST) can be regarded as a neurocognitive endophenotype, connected
with the activity of prefrontal cortex (PFC) in schizophrenia and in bipolar
illness. Dopaminergic transmission at D1 receptors (DRD1), brain-derived
neurothrophic factor (BDNF) and glutamatergic system have been shown
important for optimal PFC activity. The Src-family tyrosine kinase Fyn plays
a key role in the interaction between BDNF and glutamatergic receptor
NMDA.
Method: The study included 138 patients with schizophrenia and
111 patients with bipolar illness. They have been assessed on WCST,
where the number of perseverative errors (WCST-P), non-perseverative
errors (WCST-NP), completed corrected categories (WCST-CC), conceptual
level responses (WCST-%CONC) and set to the first category (WCST-1st CAT)
were estimated. Genotyping was done for the -48 A/G polymorphism of
the DRD1 gene, Val66Met polymorphism of BDNF gene and IVS10+37T/C
and Ex12+894T/G) polymorphisms of the Fyn gene.
Results: Schizophrenic patients with G/G genotype of DRD1 polymorphism obtained significantly worse results on WCST-CC and WCST-1st
CAT, and patients with T/T genotype of T/C polymorphism and T/T genotype of T/G Fyn polymorphism scored significantly worse on WCST-P than
patients with remaining genotypes. Differences in WCST performance in
relation to polymorphism of DRD1 and Fyn gene were not found in bipolar patients. On the other hand, bipolar patients with Val/Val genotype of
BDNF obtained significantly better results on WCST-P, WCST-CC and
WCST-%CONC compared to those with Val/Met genotype. No such difference was observed in schizophrenic patients.
Conclusion: We found a significant relationship between the performance on WCST and DRD1 and Fyn polymorphism in schizophrenia and
BDNF polymorphism in bipolar illness. This may suggest a primary importance of dopaminergic and glutamatergic system for PFC activity in
schizophrenia, and of BDNF system in bipolar illness
References: 1. Rybakowski JK, Borkowska A, Czerski PM. Kapelski P,
Dmitrzak-Weglarz M, Hauser J. An association study of dopamine receptors polymorphisms and the Wisconsin Card Sorting test in schizophrenia.
J Neural Transm 2005, 112, 1575-1582. 2. Rybakowski JK, Borkowska A,
Skibinska M, Hauser J. Illness-specific association of val66met BDNF polymophism with performance on Wisconsin Card Sorting test in bipolar
mood disorder. Mol Psychiatry 2006, 11, 122-124.
S-19
Genetic and developmental risk factors for
mood disorders and suicide
T9 Genetics
S-19-01
Gene expression and genetic variation in postmortem
tissue of depressed patients
Gustavo Turecki
McGill Group f. Suicide Studies, Douglas Hospital, Psychiatry, Canada
Introduction: Major depressive disorder and suicide are complex phenomena on which biological factors play an important role. Parallel
screening of gene expression alteration of thousands of genes makes it
possible to investigate, at the genomic level, complex disorders and gain
insight into biological mechanisms mediating risk. The goal of my presentation will be to present data suggesting that the polyamine system plays
a role in major depression and suicide
Method: Brain gene expression analysis using the Affymetrix HG-U133
chipset A and B was performed using RNA isolated postmortem from 17
cortical and subcortical brain regions from 46 male subjects, including sui-
38
cides with and without major depressive disorder and normal controls.
Follow up studies were carried out by means of RT-PCR, immunohistochemistry and western blotting. Genetic variation studies were carried out
in a sample of suicide completers from the general Quebec population
and matched controls.
Results: Our initial studies implicated SSAT in suicide and major depression. Follow up studies validated a downregulation of this gene.
Subsequent studies in additional samples confirmed our initial results and
indicated global brain alterations of SSAT and other components of the
polyamine system.
Conclusion: Polyamines constitute and interesting candidate system in
depression and suicide. Additional studies should be carried out to better
characterize and replicate our findings.
S-19-02
Neuropathology of mood disorders and effects of moodstabilizing treatments
Trevor Young
Canada
Introduction: While new effective treatments continue to emerge for
patients with bipolar disorder, the specific pathophysiological mechanisms which underlie this illness have remained somewhat elusive. A
major breakthrough in our understand occurred with the findings that
mood stabilizers have multiple effects on signal transduction pathways.
This led us to focus on a number of target genes, may of which are
involved in neuroplasticity and neuroprotection
Method: The author will describe work from his lab using postmortem
brain tissue which have shown evidence of cell loss and damage in critical brain regions. Complementary studies in cellular and animals models
will also be presented.
Results: Altered neuroplasticity and decreased cell density appears to
occur in specific pre-frontal and limbic regions from patients with bipolar
disorder. These findings may be due to decreased levels or expression of
a number of neurotrophic factors. These processes are also targeted by
mood stabilizing drugs, particularly lithium and valproate. Newer work
has emerged which suggests that oxidative damage may be a key part of
the process.
Conclusion: Much progress has been made in our understanding of the
neuropathology of mood disorders. A consistent body of data has
emerged which strongly suggest a course of future study. Understanding
how metabolism or oxidative stress contributes is a particularly interesting
question for future study.
References: Wood GE, Young LT, Reagan LP, Chen B, McEwen BS. Stressinduced structural remodeling in hippocampus: prevention by lithium
treatment.Proc Natl Acad Sci U S A. 2004 Mar 16;101(11):3973-8. Shao
L, Young LT, Wang JF. Chronic treatment with mood stabilizers lithium and
valproate prevents excitotoxicity by inhibiting oxidative stress in rat cerebral cortical cells. Biol Psychiatry. 2005 Dec 1;58(11):879-84.
S-19-03
Structural brain changes and vulnerability to bipolar disorder
Tomas Hajek
Dalhousie University, Department of Psychiatry, Halifax, Nova Scotia,
Canada
Glenda MacQueen, Anne Duffy, Martin Alda
Introduction: Bipolar disorders (BD) have strong genetic underpinning.
Presence of specific susceptibility alleles may lead to expression of biological abnormalities, which develop prior to illness onset and increase susceptibility to the disorder. It is not clear which of the neuroimaging
changes convey vulnerability to BD and which are secondary to the burden of the illness or treatment. Magnetic resonance imaging (MRI) volumetric studies in unaffected relatives of bipolar patients, first-episode
patients, pediatric BD, where the effects of the disease or treatment are
minimal showed a number of abnormalities, only some of which (striatum
volume increase, amygdala and white matter volume decrements) have
been replicated. Studies in familial bipolar disorder, where genetic risk
factors should be concentrated repeatedly showed decreased subgenual
cingulate volumes. Proton magnetic resonance spectroscopy (MRS) studies early in the course of illness are scarce and with even fewer replications (decreased dorsolateral prefrontal NAA/Cr, increased anterior cingulate myo-inositol).
GENETICS - Symposia
Method: We have been searching for biological vulnerability markers

using the high-risk (HR) design.The HR offsprings are recruited from families multiply affected with BD. Suitable families are identified through
adult probands with bipolar I or II disorder who participated in ongoing
genetic studies. Probands, their offspring and multiple other relatives are
interviewed by two research psychiatrists blind to the identity of the person, according to SADS-L format. Diagnoses are based on blind consensus review in accordance with both DSM-IV and Research Diagnostic
Criteria. High-risk offspring also undergo MRI, MRS and/or neurocognitive
testing.
Results: MRI, MRS study in 19 affected, 21 unaffected HR subjects and
31 controls matched by age and sex found comparable levels of choline,
creatine, myo-inositol, N-acetyl aspartate, glutamine/glutamate in medial
prefrontal cortices between the groups. Preliminary analyses show no differences in volumes of gray, white matter or rates of T2 hyperintensities
between the groups. These findings are congruent with unimpaired neurocognitive performance in a larger, overlapping group of high-risk individuals.
Conclusion: We found no gross neuroanatomical, or frontal lobe neurochemical abnormalities in HR subjects. Some of the previously reported
changes may be due to confounders (comorbidity, current medication,
mood state). It is also possible that vulnerability markers of BD may be
more pronounced in different areas of the brain or may affect processes
not quantifiable by MRS/MRI techniques. To address this hypothesis, we
are performing detailed MRI volumetric analyses and neurocognitive tests
targetting other brain areas.
S-27
Genetics in psychiatry
S-19-04
Genetic vulnerability to mood disorders in view of clinical
and pathophysiological heterogeneity
Jorge Ospina-Duque
Universidad de Antioquia, Departamento de Psiquiatria, Medellin,
Colombia
Grupo de Investigacion en Psiq Universidad de Antioquia
Martin Alda
Canada
Introduction: Studies of bipolar disorder often lead to conflicting results.
While equivocal findings in research are common and can be often attributed to chance alone, some of the controversies can be also interpreted
as a consequence of heterogeneity of bipolar disorder. Studies of unselected patient populations can lead to different outcomes depending on
the representation of individual bipolar subtypes in particular clinical sample.
Method: Selective review of literature on phenotypic dimensions of bipolar disorder. Against this background I will review findings from genetic
and prospective high-risk studies of bipolar disorder.
Results: The main division lines in broadly defined bipolar disorder separate groups of patients characterized for clinical course (episodic vs.
chronic, non episodic), family history, presence of non affective psychiatric
comorbidity, and response to long term treatment. Moreover, these
dimensions are correlated, not independent. One subgroup of patients is
characterized by episodic clinical course, low comorbidity rates, family history of bipolar disorder, and by favourable treatment response to prophylactic lithium. Another group of patients shows presence of residual
symptoms in remission, family history of disorders in the psychotic spectrum; such patients commonly require long-term antipsychotic treatment
to stabilize and are found more often in family samples positive for linkage
to 8p, 13q, or 22q, the regions of overlap between bipolar disorder and
schizophrenia (1). Finally, patients with mood lability, rapid cycling, with
associated symptoms of anxiety and impulsivity appear to form a third
group; these characteristics have been observed in patients with evidence
of linkage to 18p (2). The latter two subtypes may be overrepresented in
samples recruited in tertiary-care facilities. In prospective high-risk studies
of children of bipolar parents we observed similar pattern of clinical
course, co morbidity and treatment response with inter generational
transmission of these traits (3)
Conclusion: The heterogeneity of bipolar disorder may account for contradictory research findings and should be considered in a design of
genetic and neurobiological studies.
References: 1. Potash JB et al. Suggestive linkage to chromosomal
regions 13q31 and 22q12 in families with psychotic bipolar disorder. Am
J Psychiatry 2003; 160: 680-686. 2. MacKinnon DF et al. Bipolar disorder
and panic disorder in families: an analysis of chromosome 18 data. Am J
Psychiatry 1998; 155: 829-831. 3. Duffy A et al. A prospective study of
the offspring of bipolar parents responsive and nonresponsive to lithium
treatment. J Clin Psychiatry 2002; 63: 1171-1178.
T9 Genetics
S-27-01
Alternative strategies for genetic research in schizophrenia
Florence Thibaut
University Hospital Ch Nicolle, INSERM U 614, Rouen, France
Genetic studies in schizophrenia have confirmed the importance of genes
in aetiology, but have not so far identified the relationship between
observed genetic risks and specific DNA variants, protein alterations or
biological processes. Studies aiming to identify susceptibility genes for
schizophrenia are faced with the confounds of subjective clinical criteria
and the likelihood of allelic and locus heterogeneity. Search for genetic
susceptibility in complex polygenic disorders such as schizophrenia might
be improved by the identification of intermediate phenotypes related to
more fundamental aspects of brain development and function or by the
study of chromosomal aberrations associated with psychiatric symptoms.
Different examples of these strategies will be discussed.
S-27-02
Physiopathological model for bipolar disorderfrom genetic
findings
Introduction: Bipolar Disorder is heterogeneous syndrome that has an

important genetic component. It is expected that some genes that participate in neurodevelopment will play a role in its etiology. We conducted
three studies in which are possible to relate with this hypothesis. The first
with neuropsychological approach, the second related with the brain
derived neurotrophic factor (BDNF), and the last one is a genome scan in
a homogeneous population.
Method: We made a neuropsychological evaluation of 50 controls and
50 patients. A wide protocol was applied to asses the cognitive functions. We examined a sample of 224 bipolar patients and available parents (comprising a total of 212 nuclear families) ascertained in a
Colombian population isolate. We tested for transmission distortion to
bipolar patients of alleles at the rs6265 polymorphism and at a
microsatellite marker 1.3 kb away from this SNP. We performed a whole
genome microsatellite marker scan in six multiplex families with bipolar
disorder ascertained in the same population.
Results: We get a deficit in semantic memory, attention and language,
which could be an endophenotype of dysfunction in some cortical and
subcortical areas. Significant excess transmission of the rs6265 G allele
to cases was observed. Two-locus haplotype analysis showed a significant
global transmission distortion with an excess transmission of a haplotype
comprising the rs6265 G allele and microsatellite allele 227. These results
are consistent with previous studies pointing to a role for BDNF in susceptibility to mood disorders. The most consistent linkage results from parametric and non-parametric analyses of the Colombian scan involved
markers on 5q3133, a region implicated by the previous studies of BP in
Costa Rica. Interestingly, this region has been implicated in several previous genetic studies of schizophrenia and psychosis, including disease
association with variants of the enthoprotin and gamma-aminobutyric
acid receptor genes.
Conclusion: All these finding will be discussed and related whit the neurodevelopmental role in the etiology of Bipolar Affective Disorder.
References: Kremeyer, B. et al. Transmission Distortion of BDNF Variants
to Bipolar Disorder Type I Patients from a South American Population
Isolate. American Journal of Medical Genetics Part B (Neuropsychiatric
Genetics) 141B:435-439 (2006) Herzberg, I. et al. Convergent linkage
evidence from two Latin-American population isolates supports the presence of a susceptibility locus for bipolar disorder in 5q31-34. Human
Molecular Genetics, 2006, Vol. 15, No. 21 3146-3153.
39
GENETICS - Symposia
S-27-03
Molecular genetic of bipolar disorder
Alejo Corrales
Introduction: Bipolar disorder is a neurobiologically based disorder with
a multifactorial etiology that includes both genetic (multiple genes interacting with each other) and environmental components. And its heritability is increased as high as 0.8. The mode of transmission is complex.
Family studies provide consistent evidence of familiar aggregation of
bipolar disorder; twin and adoption studies point to genes as an important cause of this familiar resemblance. Risk is increased approximately
7 fold in first-degree relatives The aim is to discuss the recently findings in
genetics of bipolar disorder.
Method: We performed a theoretical research on the last findings
published by various researchers of bipolar disorder .
Results: No specific genes have been identified for bipolar disorder.
However linkage and association studies have provided strong evidence
of genes contribution to this complex disease. Linkage studies have identified several potential bipolar susceptibility loci (2p, 4p, 4q, 6q, 8q, 11p,
12q, 13q, 16p, 16q, 18p, 18q, 21q, 22q and Xq), among the recently
reported candidate genes. BNDF, AKT1, GRIN2A, XBP1, GRK3, HTR4,
IMPA2 and GABRA1 may have some importance. We will discuss the
recently findings in genetics of bipolar disorder.
Conclusion: Various loci have been identified by linkage studies which
have shown that these loci are potentially susceptible to bipolar disorder.
This has make possible that candidate genes emerge from theses loci. On
the other hand, controversial results come up from functional cloning; in
this way the first positive results found could not be replicated.
References: 1.Craddock N, Forty L. (2006). Genetics of affective (mood)
disorders. Eur J Hum Genet. 14(6): 660-8. 2.Hayden EP, Nunberger JI
Jr. (2006). Molecular genetics of bipolar disorder. Genes Brain Behav.
5(1):85-95 3.Kato T, Kuratomi. G., Kato N. (2005). Genetics of bipolar
disorder. Drugs Today. 41(5): 335-44. 4.Payne JL, Potash. J., DePaulo JR
Jr (2005). Recent findings on the genetic basis of bipolar disorder.
Psychiatr Clin North Am.28(2): 481-98, ix. 5.Smoller JW, Finn. C. (2003).
Family, twin, and adoption studies of bipolar disorder. Am J Med
Genet. 123C(1): 48-58.
S-27-04
Correlation between the short serotonin transpoting gene
and various psychiatric disorders with depressive symptom
Patricia Chieri
Association of Biological Psychiatry Secretary, Buenos Aires, Argentina
Eduardo Rodriguez Garin
Introduction: To determine differences in the serotonin transporting
gene 5HHTallleles (chromosome 17-q12) between depressive patients and
control population. Evaluate clinical differences between short (SL, SS)
and large (LL) allele patients.
Method: 100 patients in Psychiatric Emergency. with depressive syndrome were studied. Personal data background, suicidal attempts, family
background, alcoholic and substance consumption, impulsivity) were
recorded. Buccal swab samples were obtained for the corresponding
5-HTTL - genotype study.
Results: We found no differences in allele distribution between control
and depressive patients. Presence of allelic short polymorphism (SS/SL)
determine early onset of depression, larger number of suicidal attempts,
aggressiveness, impulsivity, and inadequate response to antidepressants
treatment.
40
Conclusion: Patients carrying the S polymorphisms would be more vulnerable to a worse a development depression anda worse response to
antidepressive therapy (particularly SSRI). According to previous papers
and studies, we could come to the conclusion that these patients are
more severely depressed, and, therefore, have a poorer general performance
References: 1. Bech P, Gram LF, Dein E, Jacobasen O, Vitger J, Bolwing
TG 1975: Quantitative rating of depressive sates. Acta Psychiatr Scand 51:
161 - 170. 2. Heilis A, Teufel A, Petri S, Stober G, Rierderer P, Bengel D,
Lesch KP (1996): Allelic variation of human serotonin transporter gene
expression. J Neurochem 66: 2621 - 2624. 3. Greenberg BD, Tolliver TJ,
Huang SJ, Li Q, Bengel D, Murphy DL (1999): Genetic variation in the
serotonin transporter promoter region affects serotonin uptake in human
blood platelets. Am J Med Genet 88: 83 - 87. 4. Avshalom Caspi, Karen
Sugden, Terrie E Moffitt, Alan Taylor, Ian W. Craig, HonaLee Harrington,
Joseph Mc Clay, Jonathan Mill, Judy Martin, Antony Braithwaite, Richie
Poulton.Influence of the life stress on depression: Moderation by the polymorphism in the 5-HTT Gene. Science vol 331, 386 - 389 (2003).
NEUROIMAGING - Symposia
S-06
Functional imaging in schizophrenia research
strate affecting cortical-subcortical neurocircuitries. The results have direct

implications for early detection strategies as well as pharmacological
treatment interventions.
T10 Neuroimaging
S-06-01
Imaging genetics in psychiatry
Andreas Meyer-Lindenberg
NIMH, Bethesda, USA
Introduction: Many important psychiatric disorders have a strong hereditary component, posing the problem to characterize the biological
mechanisms translating from the genetic level to that of complex social
and behavioral abnormalities. The new field of imaging genetics uses
neuroimaging methods to assess the impact of genetic variation on the
human brain.
Method: Ideally, several imaging methods are used in conjunction to
achieve an optimal characterization of structural-functional parameters in
large groups of carefully screened individuals, whose genotype is then
statistically related to these data across subjects. Imaging genetics is
therefore a form of genetic association study.
Results: While still relatively novel, the emerging literature shows that
this approach can identify neural processes involved in mediating the
effect of genetic polymorphisms on psychiatric disease risk, contributing
to the understanding of the pathophysiology of these complex disorders.
We illustrate this approach using selected examples from genes involved
in risk for schizophrenia (COMT, DARPP32), depression, anxiety and violence (5-HTTLPR, MAOA).
Conclusion: Improved mechanistic understanding of psychiatric disease
provides novel targets for future therapeutic interventions and may contribute to a more accurate biologically based nosology.
References: Meyer-Lindenberg, A., and Weinberger, D.R. 2006.
Intermediate phenotypes and genetic mechanisms of psychiatric disorders. Nat Rev Neurosci 7:818-827.
S-06-02
Vulnerability to schizophrenia - insights from brain
imaging studies
Jarmo Hietala
Turku University, Department of Psychiatry, Finland
Brain imaging together with methods of basic neuroscience indicates
subtle but widespread morphological and functional changes in cortical
as well as in subcortical structures of patients with schizophrenia.
Neuroimaging methods measure a complex set of overlapping phenomena including changes related to vulnerability (trait), neurobiology of
symptoms (state: e.g. auditory hallucinations), as well as effects of other
factors such as medication or chronicity. The research addressing brain
morphology and function related to premorbid and prodromal phases of
schizophrenia as well as psychosis vulnerability in general, has only
recently started. This knowledge is of critical importance for understanding the patophysiology of schizophrenia and for developing early detection/intervention approaches. Structural brain imaging studies suggest
that some of the key brain alterations in schizophrenia are shared (usually in a milder form) by unaffected subjects at genetically enhanced risk of
schizophrenia. Emission tomographic imaging studies (PET and SPET)
during past twenty years have convincingly documented a dysregulated
striatal dopamine system in first-admission neuroleptic-naive patients
with schizophrenia. Yet, the specificity of the dopamine dysregulation to
schizophrenia/psychosis remains unproven. We conducted a set of studies
in a Finnish monozygotic and dizgotic twins discordant for schizophrenia
in order to study whether the previously observed dopamine receptor
changes are related to overt psychosis or whether they are indicators of
genetic liability for schizophrenia (Hirvonen J et al. Arch Gen Psychiatry,
62:371-8, 2005 and Hirvonen J et al . Am J Psychiatry, 163:1747-53,
2006). We found that genetic risk for schizophrenia as such is associated
with increased D2 receptor density in the caudate and increased D1
receptor density in medial prefrontal cortex, superior temporal gyrus, and
inferior parietal lobe. These inter-related phenomena are also associated
with deficits of cognitive function suggesting a common inherited sub-
S-06-03
PET studies on the pathophysiology and pharmacotherapy
of schizophrenia
Tetsuya Suhara
Molecular Neuroimaging Group, Molecular Imaging Center, Chiba,
Japan
Since the pathophysiology of schizophrenia have been discussed with a
functional alteration of dopaminergic transmission in the brain, we have
focused the dopaminergic components for the research target of schizophrenia using PET. Dopamine receptors receive signals from presynaptic
terminal of dopamine neuron. Those are classified into five subtypes, and
selective ligands have been developed for D1 and D2 subtypes. An
increasing body of evidence favors a crucial role of extrastriatal regions in
the pathophysiology of positive symptoms, and the extrastriatal D2 receptor is expected to be the common site of action of antipsychotics. Using
high affinity ligand [11C]FLB 457, we found reduced D2 receptor binding
in the anterior cingulate cortex of patients with schizophrenia, and a significant negative correlation was observed between D2 receptor binding
and the positive symptom score. Subregions of interest were defined on
the thalamus using individual magnetic resonance images. D2 receptor
binding was also lower in the central medial and posterior subregions of
the thalamus in patients with schizophrenia. Based on the recent findings,
cortical D2 receptor may interact with GABA system working to modulate
DA release, while thalamic D2 receptor is likely to participate in sensory
gating function over the prefrontal cortex. We have found decreased D2
receptor in the anterior cingulate cortex and thalamic subregions of the
patient with schizophrenia. These observations could lead to the view
that alterations of extrastriatal D2 receptor is involved in dysregulation of
DA release and sensory signals from the thalamus to the cortex. Excessive
excitatory signals from the thalamus might flow into the cortical neural
system that modulates DA release, aggravating dysregulation of DA in
both the striatal and extrastirital regions in schizophrenia. These notions
suggest the needs of the future investigations of the extrastriatal D2
receptor function to gain the important cue for the pathogenesis and
possible treatments of schizophrenia. On the other hand D1 receptor
binding was found to be lower in the prefrontal cortex and a significant
negative correlation was observed between D1 receptor binding and the
negative symptom score. Abnormality of D1 receptor function would be
at the bottom of the negative symptoms and cognitive impairment of
schizophrenia.
S-06-04
How do antipsychotics work in our patients brains?
Lessons from PET studies
Gerhard Grnder
RWTH Aachen University, Psychiatry and Psychotherapy, Germany
Introduction: With new high affinity PET ligands for D2/D3 dopamine
receptors such as [18F]fallypride (FP) it is now possible to study not only
the striatal but also the extrastriatal binding of antipsychotics.
Method: D2-like DA receptors were quantified with FP-PET in 59 patients
suffering from schizophrenia (DSM-IV). 11 were treated with aripiprazole,
15 with clozapine, 10 with quetiapine, and 15 with ziprasidone. 8 agematched drug-free patients served as control group. All subjects underwent dynamic PET scans over 180 minutes. Patients treated with aripiprazole were scanned after varying time points after the last drug administration (range 5-78 h). Binding potentials (BP) were calculated by means
of the simplified reference tissue model. Occupancy was calculated as
percent reduction in BP of treated patients relative to controls. Plasma
concentrations and percent binding data were fit to a simple one-site
ligand binding model by nonlinear regression.
Results: Mean D2/D3 receptor occupancy was significantly higher in aripiprazole-treated patients than in all other patient groups. Occupancy was
intermediate in patients treated with ziprasidone, and lowest with clozapine and quetiapine. While aripiprazole almost saturated D2/D3 receptors
41
in all brain regions, clozapine and quetiapine did not occupy more than
60% of striatal D2/D3 receptors. These two compounds displayed preferential extrastriatal binding over the whole range of plasma concentrations. Preferential extrastriatal binding was lost at higher plasma concentrations in patients treated with ziprasidone.
Conclusion: Clozapine and quetiapine occupy a maximum of 40-60% of
striatal D2-like dopamine receptors even at extremely high plasma levels,
which is most likely explained by their low affinity rather than their rapid
dissociation (koff) from the D2 receptor. Aripiprazole due to its high affinity to D2/D3 receptors and its long half-life of about 72 hours at clinical
doses occupies very high amounts of its target receptor homogenously
throughout the brain; dissociation from those receptors is very slow.
Preferential extrastriatal binding seems to especially characterize compounds with low affinity for D2/D3 receptors; high-affinity compounds
loose their preferential extrastriatal binding at high plasma concentrations.
S-26
Neuroimaging advances in psychiatry
T10 Neuroimaging
S-26-01
Serotonin transporter imaging and the treatment of
affective disorders
Siegfried Kasper
N. Klein, R. Lanzenberger, C. Spindelegger, M. Willeit, J. Sacher,
N. Mossaheb, R. Dudczak, S. Asenbaum, T. Attarbaschi, A. Holik,
J. Tauscher
With the introduction of the antidepressants over 50 years ago it become
evident that the serotonin-(5-HT) system should play a significant role
both in the pathophysiology and the treatment of depression. Peripheral
measurements, like the serotonin transporter activity in the blood platelet
gave the first hint of a serotonin pathology in depression. Thereafter, neuroendocrine challenge methods like the ones with fenfluramine, mcPP or
citalopram indicated a serotonin deficiency in depression, since the hormones studied after the exposure to the before mentioned chemicals
demonstrated a blunted response compared to healthy controls. More
specifically, brain-imaging methods using PET (DASB) as well as SPECT
(-CIT, ADAM) focused on 5-HT transporter activity and most studies,
which were rigorously performed, demonstrated a lower serotonergic
activity in specific brain areas. The serotonin transporter (SERT, 5-HTT) is
the primary target for selective serotonin reuptake inhibitors (SSRI), which
are commonly used for treatment of major depression and anxiety disorders. Occupancy rates for various SSRIs with the PET ligand [11C] DASB
have been found to be between 70% and 85% in a dose dependent
manner. Furthermore, it emerged that the in vitro EC50 does not correlate with affinity. This indicates that although target-specific affinity is
obviously a very important feature of a drug, it does not predict the occupancy value in vivo, even when plasma levels are known. As an example,
we studied the binding properties of citalopram compared to escitalopram and found that the significantly higher SERT-occupancy after multiple doses of escitalopram compared to citalopram indicates a more complete inhibition of SERT by escitalopram. Since the concentration of the
S-enantiomer was essentially the same, the lower occupancy seen with
citalopram cannot be explained by a competitive interaction of the Renantiomer at the primary site of the SERT. We discussed that the higher
occupancy of escitalopram may be due to an allosteric mechanism, e.g. a
specific mechanism on the 5-HTT. Further studies of the 5-HTT as well as
the other monoamine transporter activities and monoamine receptors
and their pharmacological influence of different antidepressants could
further help to characterize the clinical efficacy of various compounds in
translational research. Additionally, pharmacogenetic approaches will
thereafter link the specific treatment responses to biological variables.
The future will teach us, that antidepressants should be prescribed in a
target specific manner, based on the available genetic characteristics (like
the known polymorphism) as well as the current status of biological variables, e.g. the activity of 5-HTT. With this approach we could reduce the
number of initial nonresponders.
42
S-26-02
The emerging role of neuroimaging in drug development:
From biomarker for on-target pharmacology to surrogate
endpoint for the prediction of treatment response
Johannes Tauscher, MD
Translational Imaging Group, Lilly Research Laboratories, Indianapolis,
IN, USA
Over the last two decades, various new applications for imaging technologies in the neurosciences have emerged. Radio labeled tracers for PET
and/or SPECT can be used as biomarker in drug development (1) to assess
the distribution and concentration of a particular target (e.g. neurotransmitter receptor, beta-amyloid plaque, etc.); (2) to determine the target
occupancy of a therapeutic compound by quantitatively analyzing the
drug induced tracer displacement from the target; (3) to analyze the distribution of a very low dose (< 1 mg) of a radio-labeled drug (PET micro
dosing) to confirm brain penetration, and (4) to study drug induced
changes in brain glucose metabolism (e.g. FDG-PET) or regional cerebral
blood flow (HMPAO SPECT) as a proxy for brain activation or deactivation during treatment.
These Imaging biomarker studies can potentially provide evidence that:
a novel drug reaches a specific drug target in rodents (micro-PET),
non-human primates and/or humans
a mechanism is relevant to pathophysiology
a drug can be used to treat a disease in humans
Imaging biomarkers are a key tool not only to enable better and quicker
drug discovery and clinical drug development, they also are pivotal in
implementing are more targeted approach to find the right dose of the
right drug for right patient.
S-26-03
Jose Alexandre Crippa
Sao Paulo University, Hospital Das Clinicas, Ribeirao Preto, Sao Paulo,
Brazil
S-26-04
Population-based volumetric brain measurements in psychotic disorders: MRI studies at the disease onset and after
one year
Geraldo Busatto
Universidade de Sao Paulo, Psiquiatria, Brazil
Maristela Schaufelberger, Fabio Luis de Souza Duran, Marcia Scazufca,
Edson Amaro Jr., Claudia Costa Leite, Robin M. Murray, Philip K.
McGuire, Paulo Rossi Menezes
Introduction: Patients with schizophrenia in developing countries are
reported to experience better outcomes than those in developed countries. This raises the question whether the biological basis of the disorder
is the same in the two types of countries. However, most magnetic resonance imaging (MRI) studies of psychosis have been carried out in developed countries.
Method: We have conducted a morphometric MRI investigation in a
sample of 122 subjects with first-onset psychosis living in a circumscribed
geographical region of the city of Sao Paulo, Brazil, compared their mean
regional brain volumes to those of 94 asymptomatic subjects randomly
selected from the same geographical areas. MRI processing was performed using voxel-based morphometry (VBM).
Results: There were significant decreases in grey matter in first-episode
psychosis subjects relative to controls in the left superior temporal and
inferior prefrontal cortices, insula bilaterally and the right hippocampal
region (p<0.05, corrected for multiple comparisons). Patients with schizophrenia (n=62) exhibited a similar pattern of decreases in grey matter relative to controls as the first-episode psychosis group.
Conclusion: These results indicate that first-episode psychosis patients in
our environment present patterns of significantly decreased gray matter
relative to controls in the same fronto-temporal regions as seen in MRI
studies conducted in high-income nations. This suggests that the
supposedly distinct outcomes of schizophrenia between developing and
high-income countries are not related to differences in the patterns of
brain abnormalities at the first episode of the disorder. We are currently

completing the data collection of a follow-up MRI evaluation of the above
psychosis cases and a proportion of controls, one year after their first contact with mental health services. Such follow-up study will allow us to
investigate the longitudinal course of brain abnormalities in patients with
psychosis in Brazil. In addition, given that a proportion of these subjects
have had only intermittent pharmacological care for their condition, we
expect to be able to investigate whether brain abnormalities in subjects
who remain poorly treated for large periods of time are greater in comparison to those found in subjects who have remain under regular treatment.
S-39
Neuroimaging correlates of psychotic
symptoms
T10 Neuroimaging
S-39-01
Behavioral neuroimaging in psychiatry and psychotherapy
Frank Schneider
Dept. of Psychiatry, Aachen, Germany
Introduction: Neuroimaging has proved its capability to show structural
and functional disturbances in psychiatric diseases. Especially functional
imaging provides new insights into the correlates between brain and
behavior in mental diseases. Behavioral disturbances in psychiatric disorders are most often found in cognitive and emotional processes. In schizophrenia for example affective disturbances are amongst the most prominent symptoms. Functional imaging helps us to assess the neural basis of
these disturbed emotional processes. To gain further knowledge about
the neural correlates of these symptoms, different samples of schizophrenia patients have been investigated by functional Magnetic Resonance
Imaging (fMRI). Studies in juvenile schizophrenics, early-onset patients
and other subgroups of schizophrenia patients have shown stable characteristic dysfunctions in the cerebral networks underlying emotional
processes, such as emotion recognition and emotional experience.
Furthermore functional disturbances of regions modulating the interaction between emotion and cognition could be observed during working
memory demands. In these studies the most prominent findings were in
subcortical (esp. the amygdala) and in prefrontal areas. But functional
imaging has also been shown as a useful tool in illustrating the brainbehavior-relation of therapeutic interventions. Further advances in our
knowledge about psychiatric diseases will not only rely on a closer look at
the differences between specific syndromes in psychiatric diseases but will
also depend on the application of technical advancements. The sensitivity
of functional imaging will enhance an even better assessment of psychotherapeutic interventions. These new advances will comprise
enhanced protocols for data acquisition, new imaging paradigms, innovative approaches in the analysis of functional and strutural data as well
as adequate methods ensuring the quality of the data. All this will provide
new insights in the pathophysiology, the diagnosis and therapy of mental
diseases.
S-39-02
Gamma band oscillations and disordered perception and
cognition in schizophrenia
schizophrenia patients (SZ) and 20 healthy control subjects (NC), who

pressed separate buttons to indicate perception of an illusory square or its
absence. Phase-locking was used as a measure of neural synchrony in the
EEG, and was computed separately on stimulus-locked and responselocked single trials. The Morlet wavelet transform was applied to the 20100 Hz frequency range of the EEG on correct-response trials for stimulus-locked epochs and response-locked epochs (response onset was start
of the epoch). Confirming our previous study, SZ failed to show a stimulus-locked gamma oscillation in occipital electrodes. In what we believe to
be a novel finding of the present study, both NC and SZ showed an oscillation that was phase-locked to reaction time. However, the frequency
band of this oscillation was significantly lower in SZ (22-24Hz) than in NC
(31-44Hz). Furthermore, the stronger this abnormal frequency band of
phase-locking, the more SANS/SAPS/PANSS visual hallucinations, thought
disorder, and disorganization in the SZ. There were no correlations with
medication.The RT-locked oscillation may reflect processes associated
with conscious perception and feature binding of the stimuli prior to
response. These data suggest that, while synchronization must occur for
perception of the Gestalt, it occurs at a lower frequency in SZ due to a
reduced capability of neural networks to support high-frequency synchronization, an abnormality strongly associated with fundamental SZ symptoms. These data support our hypothesis of a fundamental deficit in SZ
neural circuitry supporting synchronization, which we suggest may be
related to abnormalities in NMDA neurotransmission and inhibitory
interneurons (Grunze et al., J. Neurosci., 1996; McCarley et al.,
Eur.Arch.Psych.Clin.Neurosci., 1999).Subsequent work has obtained evidence for steady-state gamma band abnormalities in manic psychosis,
which other data suggest may be state-related. Moreover individuals with
schizophrenia show a left laterality not present in manic psychosis.
S-39-03
Auditory hallucinations in schizophrenia - what makes
them real experiences?
Peter W. Woodruff
University of Sheffield, Academic Clinical Psychiatry, Sheffield, South
Yorkshire, United Kingdom
The propensity to hallucinate represents a natural characteristic of the
human brain. Rarely, except in severe neuropsychiatric conditions such as
schizophrenia, do hallucinations naturally predominate (Woodruff, 2004).
The neural basis of auditory verbal hallucinations has been investigated
using structural and functional neuroimaging techniques. So far, no studies have defined a model that explains why auditory hallucinations are
perceived in the absence of an external auditory stimulus.Recent
advances using functional MRI that allow us to examine spontaneous
activity of auditory cortex in health [in acoustic silence] go some way
towards enabling us to define such a model (Hunter et al., 2006). I will
discuss some recent neuroimaging research into the pathogenesis of
auditory hallucinations, which seeks to examine component perceptual
processes that lead to an individuals perception of auditory hallucinations
as real auditory events in the absence of external auditory signals.
References: Woodruff PWR (2004). Auditory hallucinations - insights and
questions from neuroimaging. Cognitive Neuropsychiatry 9 (1-2): 73 - 91
Hunter MD, Eickhoff S, Miller T, Farrow TFD, Wilkinson ID, Woodruff
PWR. (2006) Neural Activity in speech-sensitive auditory cortex during
silence. Proceedings of the National Academy of Sciences of the United
States of America Vol 103: 572-578
Robert W. McCarley
Harvard va med ctr, Psychiatry, Brockton MA, USA
Many current views of schizophrenia, including our own, suggest that it
results from abnormalities in neural circuitry, but empirical evidence in the
millisecond range of neural activity has been difficult to obtain. We previously demonstrated that schizophrenia is associated with abnormal patterns of stimulus-evoked phase-locking of the EEG in the gamma band
(30-100 Hz; Spencer et al., J. Neurosci., 2003). These patterns may reflect
impairments in neural assemblies, which have been proposed to use
gamma band oscillations as a mechanism for synchronization.In one study
to be described here we used a visual gestalt stimulus in 20 chronic
43
S-39-04
Dysfunctions of the language loop in schizophrenic
thought disorders and hallucinations
Werner Strik
University Hospital of Psychiatry, Berne, Switzerland
Mapping of psychotic symptoms on dysfunctions of specialized brain circuits requires a comprehensive understanding of the structural and functional abnormalities. Left hemispheric language related brain regions
show a complex pattern of structural and functional changes at rest and
during activation in schizophrenia. Arterial spin labeling (ASL), an MRI
method to measure regional prefusion, is apt to add important information about the functional dynamics of the language loop during thought
disorders and verbal hallucinations. First results will be presented.
S-39-05
Corollary discharge and auditory hallucinations
Daniel Mathalon
Yale University / VACHS, Psychiatry 116a, West Haven, USA
Judith Ford
Introduction: Synchronization of neural activity preceding self-generated
actions may reflect the operation of forward model, which acts to dampen
sensations resulting from those actions. If true, pre-action synchrony
should be related to subsequent sensory suppression. Deficits in this
mechanism may be characteristic of schizophrenia and related to positive
symptoms, such as auditory hallucinations. If true, schizophrenia patients
should have reduced neural synchrony preceding movements, especially
patients with severe hallucinations.
Method: In 24 patients with schizophrenia or schizo-affective disorder
and 25 healthy controls, we related pre-speech neural synchrony to subsequent auditory cortical responsiveness to the spoken sound, compared
pre-speech neural synchrony in schizophrenia patients and healthy controls, and related pre-speech neural synchrony to auditory hallucination
severity in patients. To assess neural synchrony, phase coherence of singletrial electroencephalography (EEG) preceding talking was calculated, at a
single site, across repeated trials. To assess auditory cortical suppression,
the N1 event-related brain potential to speech sound onset during Talking
and Listening were compared.
Results: In healthy controls, pre-speech neural synchrony was related to
subsequent suppression of responsiveness to the spoken sound as reflected in reduction of N1 during Talking relative to Listening. There was
greater pre-speech synchrony in controls than in patients, especially those
with severe auditory hallucinations.
Conclusion: These data suggest EEG synchrony preceding speech reflects
the action of a forward model system, which dampens auditory responsiveness to self-generated speech and is deficient in patients who hallucinate.
44
PSYCHOPHARMACOLOGY - Symposia
S-08
Neuropsychobiology and pharmacotherapy of
nonorganic sleep disorders
T11 Psychopharmacology
S-08-01
Sleep and stress regulation in children: Impact of prediction in psychiatry
Martin Hatzinger
University Hospital Basel, Psychiatric Outpatient Clinic, Switzerland
S. Brand, S. Perren, S. Stadelmann, A. von Wyl, K. von Klitzing
Introduction: Introduction: Sleep regulation and hypothalamic-pituitaryadrenocortical (HPA) system function are associated with psychiatric disorders such as depression. However, most of the data available so far are
from studies after the disorders onset. Thus, we started a project in children aiming to investigate sleep regulation, HPA axis function, and psychological/behavioural variables in order to identify risk factors early in
development. Here, we report the first cross-sectional investigation.
Method: Methods: 67 pre-schoolers (35 boys and 32 girls) at the age of
5 years underwent sleep EEG-monitoring according to standard procedures. Baseline HPA activity was assessed by the use of saliva morning
cortisol measurements after awakening (MC), whereas saliva samples
before, during and after psychological challenge were used to investigate
HPA function under stress conditions.
Results: Results: Boys showed significantly more REM sleep when compared to girls (p < .05). Independent of gender, cluster analysis revealed
that children labelled as bad sleepers (n = 27) showed significantly
increased MC values compared to normal sleepers, whereas good sleepers displayed the lowest MC values. Sleep EEG markers such as an
increased number of awakenings after sleep onset, more time in stage 1,
2, and in REM sleep were associated with increased cortisol values under
stress conditions. Moreover, an increased sleep efficiency was significantly
correlated with low degrees of impulsivity (p < .05), bullying and social
inhibition (p < .05), whereas a decreased sleep efficiency was significantly
correlated with the avoidance of perceiving social conflicts.
Conclusion: Conclusions: Our results show (1) that bad sleep is associated with heightened HPA system activity already in pre-school children,
and (2) that unfavourable sleep patterns are related to more difficult
behavioural/psychological dimensions. The longitudinal follow up will
demonstrate if these biological abnormalities are predictive for the onset
of clinically relevant psychiatric problems.
S-08-02
Somatoform pain disorder and sleep
Gerda Saletu-Zyhlarz
Medical University of Vienna, Department of Psychiatry, Austria
Wolfgang Prause, Peter Anderer, Martin Aigner, Olya Mikova, Bernd
Saletu
Introduction: There is a close interaction between chronic pain and
insomnia as 2/3 of pain patients and 80% of patients with fibromyalgia
and somatoform pain disorder (SPD) suffer from sleep disturbances
(Aigner et al. 2002). Polysomnography revealed reduced deep sleep, prolonged latency to deep sleep and increased stage shifts in SPD patients vs.
controls (Saletu et al. 2005). Pain disrupts sleep while in turn insomnia
lowers the pain threshold. Insomniac pain patients suffer more from their
pain and feel greater psychosocial impairment than patients without
insomnia. Apart from sleep hygiene and psychotherapy, antidepressants
have increasingly been applied in the treatment of insomniac pain
patients. The aim of this study was to investigate the effects of trazodone
CR, a sleep-promoting antidepressant (SARI), on objective and subjective
sleep and awakening quality as well as pain measures in SPD patients
(F45.4) with nonorganic insomnia (F51.0).
Method: Fifteen patients (8 males, 7 females, aged 50.1+11 years) participated in the single-blind, placebo-controlled, cross-over study on the
acute effect of 100 mg trazodone, followed by a six-week titration period
regarding the optimum dose. Polysomnographic evaluation (PSG) was
performed by the Somnolyzer 24x7 classification program in the adapta-
tion, placebo, 1st, 41st and 42nd trazodone night. Subjective sleep and
awakening quality was determined by the Subjective Sleep and
Awakening Quality Scale, objective awakening quality by psychometry,
pain intensity and psychosocial consequences by VAS.
Results: Clinical evaluation demonstrated a significant improvement in
the Pittsburgh Sleep Quality Index, Beck Depression Inventory, Zung
Anxiety Scale and State/Trait Anxiety Inventory after six weeks of trazodone (155.6+39.1 mg/d). PSG showed a significant decrease in nocturnal awakenings and an increase in S3 after both acute and chronic trazodone as well as a decrease in S1 after chronic treatment. Stage shifts
between S1, S2 and wake decreased, while after chronic treatment shifts
from SREM to S1 decreased and shifts from S2 to SWS increased. Average
pain intensity improved significantly as did the detrimental effects of pain
on social and family life.
Conclusion: Acute treatment with 100 mg trazodone CR resulted in a
significant decrease in light and increase in deep sleep as well as a
decrease in nocturnal awakenings and stage shifts from S2 to wakefulness. After six weeks of titration to the optimum dose, the improvement
of objective and subjective sleep quality was associated with an improvement of pain and its psychosocial consequences in addition to a reduction
of depression and anxiety.
S-08-03
Sleep in depression and dementia: Differential diagnostic
aspects
Ulrich Hemmeter
University of Marburg, Clinic of Psychiatry, Germany
Rodrigo Rocamora, Andreas Thum, Anja Haag, Marco Giesler, Andreas
Becker, Werner Cassel, Martin Hatzinger, Juergen Christian Krieg, Edith
Holsboer-Trachsler
Introduction: In older patients who suffer from depressive symptoms
and cognitive impairment the clinical decision between the diagnoses of
depression and dementia may be difficult. In addition, patients with
dementia and depressed patients frequently show a disturbance of sleep.
Method: Polysomnographic registration of sleep in depressed patients
and patients with dementia may provide additional information for differntial diagnosis.
Results: Sleep EEG registration in depression revealed a characteristic
sleep EEG profile concerning distinct alterations of sleep architecture and
REM-sleep (reduction of SWS, increase and advance of REM-sleep). In
dementia polysomnographic assessment has been done less intensively,
mainly in patients with dementia of Alzheimer type (DAT). The most significant polysomnographic finding in DAT is a reduction of REM-sleep,
which may reflect impaired cholinergic neurotransmission. Therefore, predominantly REM-sleep variables clearly differ between depressed patients
and patients with DAT.
Conclusion: In this presentation polysomnographic data in dementia and
depression will be reviewed. In addition, own long term studies in
patients with different types of dementia and in depressed patients will
be presented. The polysomnographic findings of these studies will be discussed with respect to differential diagnosis, prediction of treatment
response and the long term course of both diseases. In addition, the
results will be related to the current knowledge of the neurochemical and
neurendocrine regulation of sleep.
S-08-04
Pregabalin in insomnia related to neurotic and stress-related disorders and sleep-related movement disorders
Bernd Saletu
Peter Anderer, Magdalena Mandl, Georg Gruber, Halina Divos, Gerda
Saletu-Zyhlarz
Introduction: Pregabalin is a novel CNS drug, which blocks high-voltage
activated calcium channels, thereby reducing the release of glutamate,
nordrenaline and substance P (1). Thus, the drug is not only interesting
for treating epilepsy and neuropathic pain but also anxiety (2) and sleeprelated movement disorders such as restless legs syndrome (RLS) and periodic limb movements during sleep (PLMS), which have been shown to
45
react beneficially to anticonvulsants in addition to dopaminergic compounds (3-5). The aim of this study was to investigate the acute effects of
pregabalin on objective and subjective sleep and awakening quality in
insomniac patients with neurotic and stress-related disorders and comorbid RLS and PLMS.
Method: In the single-blind, placebo-controlled cross-over study,
13 patients (6 females, 7 males aged 47.4+12.2 years) with the diagnosis of nonorganic insomnia (ICD-10: F51.0) related to adjustment disorder
(F43.2, n: 6), generalized anxiety disorder (F41.1, n: 4), posttraumatic
stress disorder (F43.1, n: 2) and mixed anxiety and depression (F41.2,
n: 1) were included. All patients exhibited sleep-related movement disorders (9 RLS, 4 PLMS). Polysomnographic and psychometric measures were
obtained in 3 subsequent sleep laboratory nights (adaptation, placebo
and pregabalin 1 mg/kg).
Results: As compared with placebo, pregabalin significantly improved
total sleep time, sleep efficiency, wake during the total sleep period and
the frequency of nocturnal awakenings (p<0.05, Wilcoxon). Concerning
sleep architecture, it decreased S1 and increased S3 and S4 while shortening REM latency. Pregabalin tended to increase snoring and the snoring index (p<0.10) and to decrease PLM and the PLM index. PLM during
wakefulness, arousals and the arousal index were significantly decreased.
Pregabalin tended to increase arousals due to snoring, while it significantly
decreased arousals due to PLM and spontaneous arousals (p<0.05).
Subjective sleep quality was significantly improved by the drug, as were
mood and affectivity. Fine motor activity increased significantly, CFF tended
to decrease.
Conclusion: In conclusion, pregabalin has therapeutic benefits on subjective and objective sleep and awakening quality in neurotic and stressrelated disorders, but also in RLS and PLMS.
References: 1 Fink et al. Neuropharmacology 2002; 42(2): 229-236. 2
Feltner et al. J Clin Psychopharmacol 2003; 23(3): 240-248. 3 Saletu et
al. Eur Neuropsychopharmacol 2001; 11: 153-161. 4 Saletu et al. J Sleep
Res 2006; 15, Suppl 1: 92. 5 Happe et al. Neuropsychobiology 2003; 48:
82-86.
S-13
Recent update in pharmacogenetic studies
S-13-01
Recent update in pharmacogenetic studies in psychiatry
Ma-Li Wong
Miami, USA
Introduction: Molecular studies in Psychiatry still face the challenges of
established Clinical Epidemiology, while adding up to them problems pertaining to the genomics field. On the clinical side an optimum yield will
only be obtained if our data is rigorously collected. Phenotype assignment
is crucial, and while a judicious observation of our current Diagnostic
Manuals criteria is the best way to collect high quality data, we must bear
in mind that genomic tools are signaling to have the potential of reshaping established diagnostic entities. The long established importance of
familial history is being strongly revived by evidences from the laboratory,
and we can now only glimpse at other areas of the psychiatric interrogation which will intimately correlate with novel experimental findings. The
same issues apply to therapeutic areas. How adequately are traditional
methods of evaluating treatment response coping with the rigorous
demands of detailed treatment evaluations required by the area of pharmacogenetics? Are we still adequately served by categorical outcomes?
Can we move beyond traditional rating scales, and develop psychometric
instruments tailored to the challenges of present-day genetics? The work
to be done on the genetic side is just as notable. Although genome-wide
strategies stand as the way to the future, cost and feasibility issues still
reserve it to very few. The alternative option of addressing questions
through candidate approaches comes loaded with decisions to make.
Should we pursue evaluating one SNP at a time, one haplotype at a time,
one gene, or should we attempt an entire pathway at once? The unprecedented volume of information we have to deal has made bioinformatics
46
and advanced statistics an integral part of our laboratories. Although the

necessity of establishing multidisciplinary teams is unanimous, the implementation of such groups is easier said than done, and the research funding agencies have only recently adapted their policies to the magnitude
of the tasks before us. Albeit our most striking breakthroughs are probably in the future, we have already started to assemble databases and
results, specially in pharmacogenetics of antidepressants. Ma-Li Wong,
M.D. Vice-Chair for Translational Research, Department of Psychiatry and
Behavioral Sciences, University of Miami, Miller School of Medicine
S-13-02
Pharmacogenetic study of schizophrenia
Sang Woo Han
Soon Chun Hyang University, Psychiatry, Seoul, Republic of Korea
Introduction: Rapidly developing pharmacogenetics and pharmacogenomics are being recognized as means of maximizing the effect of treatment for each individual, helping select drugs that minimize side effects,
and understanding the pathophysiology of diseases.
Results: Until now, pharmacogenetic researches on schizophrenia have
been focused on functional candidate genes related to the therapeutic
effects and side effects of antipsychotics drugs. Research has been made
on dopaminergic receptors D2, D3 and D4, which are related to the clinical effect of clozapine, an atypical antipsychotic agent, and on serotonin
receptors 5-HT2A, 5-HT2C, 5-HT6 and 5-HT7 and serotonin transporter
(SLC6A4) gene. Among them, the polymorphism of 5-HT2A and
dopamine D2 receptor gene (DRD2) suggests a possible positive connection to antipsychotic efficacy on schizophrenia, so the possibility needs to
be examined.Pharmacogenetic studies on the side effects of antipsychotic
medication have been focused on tardive dyskinesia and weight gain.
Because D2 receptor gene (DRD2) is a main site on which typical antipsychotic medication works, it is a highly possible candidate but most
researches on genetic variation have produced negative results. It is
notable that the polymorphism of Ser9Gly DRD3 gene shows a relatively
consistent connection to tardive dyskinesia. In research on cytochrome
P450 genes, CYP2D6 gene variation was not relevant, but CYP1A2 polymorphism showed the possibility of a significant connection. 5-HT2A
receptor gene (HTA2A) showed a connection to TD in two separate
researches, but the results are not consistent. A common factor of
antipsychotics related to weight gain is that they are all not only histamine
H1 receptor antagonists but also 5-HT2C antagonists and 5-HT1A agonists. Investigated candidate genes include 5-HT2C, 5-HT2A and 5-HT1A
receptor genes (HTR2C, HTR2A and HTR1A), histamine H1 and H2 receptor genes (H1R and H2R), cytochrome P450 1A2 gene (CYP1A2), 3 and
1a adrenergic receptor genes (ADRB3 and ADRA1A), and tumor necrosis
factor gene (TNF-), but the results have not been consistent. Further
research is required to assess whether or not they predict weight gain.
S-13-03
Pharmacogenetic study of depressive disorders
Rhee-Hun Kang
Korea University, Seoul, Democratic Peoples Republic of Korea
Introduction: Modulations of serotonergic and noradrenergic systems
are thought to be critical to the therapeutic effect of most antidepressants, and their efficacies have been shown to depend on a functional
polymorphism within the promoter region of the serotonin transporter
gene (5-HTTLPR). Mirtazapine has a dual-action profile, combining the
enhancement of the noradrenergic neurotransmitter system with specific
actions on particular serotonergic receptor subtypes. The goal of this
study was to elucidate whether the 5-HTTLPR polymorphism is associated
with the mirtazapine antidepressant response in subjects with major
depressive disorder (MDD).
Method: One hundred and one MDD patients were evaluated during 4
weeks of mirtazapine treatment. The severity of depression was assessed
with the 21-item Hamilton Depression Rating scale, and the 5-HTTLPR
genotypes in the patients were determined using the polymerase chain
reaction.
Results: Our results showed that responses at the 2nd and 4th weeks
were significantly better for the s/s genotype of the 5-HTTLPR polymorphism than for l-allele carriers.
Conclusion: Notwithstanding these limitations, this study suggests that
the response to noradrenergic and specific serotonergic antidepressants is
significant associated with the 5-HTTLPR polymorphism, with the presence of the s/s genotype resulting in a better response to mirtazapine
treatment. We also found that the 5-HTTLPR s/s genotype acts as a predictor of an early response to the treatment of depression with mirtazapine.
S-13-04
Pharmacogenetic studies of anxiety disorders: Focused on
social anxiety disorder and panic disorder
0% (0%-14.2%) for amisulpride (n=23) and 0% (0%-10.3%) for aripiprazole (n=34). The overall incidence of pre-diabetes was 16.9% (11.8%22.5%). New onset diabetes was reversed in 11 patients following switch
to amisulpride (n=4), aripiprazole (n=7) or risperidone (n=1) and not
reversible in 1 patient switched to quetiapine.The incidence rate of ATPA metabolic syndrome was 20%, with significant differences between
antipsychotic agents. 17.2% of patients developed severe dyslipidaemia
requiring an intervention with a statin.
Conclusion: Metabolic abnormalities are frequently observed and can
occur fast after the initiation of antipsychotic medication. The liability to
induce metabolic abnormalities differs significantly between antipsychotics. The data underscore the need for screening for metabolic abnormalities in patients diagnosed with severe mental illness treated with
antipsychotics.
Se-Won Lim
Kangbuk Samsung Hospital, 108, Pyung-dong Chongro-gu, Seoul,
Republic of Korea
Kang-Seob Oh
S-28-02
Looking beyond the weight gain: Preclinical evidence of
antipsychotic - induced adiposity and pancreatic dysfunction
Introduction: The aim of this presentation is to review current research

perspectives of pharmacogenetic studies in anxiety disorders.
 Pharmacogenetics is one of the most active fields of biomedical
science in recent days. However, pharmacogenetic studies performed
specifically for anxiety disorders are still small in number.
Method: The current research and advances in pharmacogenetic studies
was extensively reviewed by searching available electronic databases. The
authors also performed some genetic and pharmacogenetic studies about
panic disorder and social anxiety disorder by using citalopram and
moclobemide. The severity of panic and social phobic symptoms was
measured before the beginning of treatment and after at least 4 weeks
of treatment.
Results: There were limited number of pharmacogenetic studies about
panic disorder and few studies about social anxiety disorders. Most studies were unreplicated report with small sample size.
Conclusion: Anxiety disorder tends to be comorbid with other anxiety
disorder and depressive disorders. Therefore, it is often hard to interpret
the relevance of pharmacogenetic studies of anxiety disorders. More studies
with large number of samples and controlling comorbidity issues are
necessary in these fields. The pharmacogenetic study of anxiety disorders
is still in its early stages
References: Binder EB, Holsboer F. Pharmacogenomics. Handb Exp
Pharmacol. 2005;(169):527-46
S-28
Management and mechanisms of antipsychotic
associated metabolic disturbances
S-28-01
Prevalence and incidence rates of metabolic abnormalities
and diabetes in a prospective study of patients treated
with second-generation antipsychotics
Marc De Hert
UPC KU Leuven, Psychotic Disorders, Kortenberg, Belgium
L. Hanssens, M. Wampers, D. van Eyck, A. Scheen, J. Peuskens
Introduction: Increased rates of medical comorbidity and mortality in the
mentally ill population are a topic of growing concern, and metabolic side
effects of psychotropic therapy are one factor that may increase this risk.
Method: All consecutive patients with schizophrenia (n=238) started on
antipsychotic medication at our university psychiatric hospital and affiliate
services were entered in an extensive prospective metabolic study including an oral glucose tolerance test and followed for 3 months.
Results: The overall incidence rate of new onset diabetes within
3 months of antipsychotic initiation was 4% (95%CI: 1.8%-7.4%, n=226).
Incidence rates by specific agent were 8.7% (1.1-%-28%) for clozapine
(n=23), 6.8% (1.9%-16.5%) for olanzapine (n=59), 6.7% (1.8%-22.1%)
for quetiapine (n=30), 1.8% (0.1%-10.3.%) for risperidone (n=57), and
Marilyn Ader
University of Southern California, Los Angeles, USA
Introduction: A common side effect of atypical antipsychotic therapy is
weight gain, with associated reports of increased risk of diabetes. Since
weight gain often reduces insulins ability to normalize blood glucose
(insulin resistance), it has been suggested that effects on weight are
the dominant metabolic disturbance caused by these agents. However,
weight gain and resistance alone are insufficient to cause diabetes
because of the feedback relationship between insulin sensitivity and
insulin secretion, such that resistance is normally overcome by hypersecretion from pancreatic <nothtml unicode=8>eta-cells. Diabetes during
antipsychotic use likely involves metabolic dysfunction beyond druginduced weight gain, although direct study of these effects has been minimal.
Method: Preclinical placebo-controlled studies were performed to examine the effects of the atypical antipsychotics olanzapine (OLZ) and
risperidone (RIS) on body weight, adiposity, insulin sensitivity, and pancreatic
function in normal dogs treated for 6 weeks. At baseline and after treatment, we measured (1) adiposity (total, visceral, and subcutaneous) by
abdominal MRI, (2) insulin sensitivity, and (3) pancreatic <nothtml unicode=8>eta-cell function using gold standard glucose clamp methods.
Results: OLZ caused weight gain similar to placebo, with no significant
change with RIS. Body weight changes did not reflect striking differences
between agents upon fat deposition. OLZ induced near-doubling of total
adiposity, with 80-100% increases in visceral and subcutaneous fat mass.
RIS effect on adiposity was modest and similar to placebo. OLZ also
induced a severe decrement in insulins ability to suppress glucose production (hepatic insulin resistance) not evident in RIS- or placebo-treated
dogs. Such resistance should engender enhanced pancreatic <nothtml
unicode=8>eta-cell function. However, no <nothtml unicode=8>eta-cell
upregulation was observed after OLZ treatment, indicating interference
with the pancreatic response necessary to compensate for insulin resistance and obesity. Drug-induced metabolic abnormalities were independent of observed changes in body weight.
Conclusion: Effects of atypical antipsychotics on body weight do not
reflect underlying metabolic effects on adiposity and insulin secretion.
Further studies are required to determine the mechanisms by which
observed defects may develop, and to quantify the effects of other agents
on factors other than body weight which can increase diabetes risk in the
psychiatric population.
S-28-03
A cross-sectional study of adiponectin in patients with
schizophrenia
Linda Hanssens
Universite de Liege, Public Health, Belgium
Marc De Hert, D. van Eyck, M. Wampers, A. Scheen, J. Peuskens
Introduction: Adiponectin is a recently identified adipocyte-derived protein associated with metabolic abnormalities such as obesity, insulin resistance and diabetes. Metabolic disorders are a growing concern in patients
treated with antipsychotic medication.
47
Method: Fasting adiponectin levels were assessed in a cross-sectional

sample of 294 patients with schizophrenia treated with antipsychotic
medication. The patients are enrolled in a prospective study evaluating
the metabolic effects of antipsychotics. All underwent an extensive metabolic screening, including an oral glucose tolerance test.
Results: Adiponectin levels are correlated with BMI, and differ significantly
between patients with normal weight, overweight or obesity (p=0.0001).
Patients meeting criteria for the metabolic syndrome, either with NCEP
ATP-III criteria (28.2%) or with the more recent IDF criteria (35.7%), have
significantly lower adiponectin levels than patients without a metabolic
syndrome (p=0.0001). Patients without glucose abnormalities (82.7%)
have significantly higher adiponectin levels compared to patients with
glucose abnormalities (IFG and/or IGT, 9.9%) or patients meeting ADA criteria for diabetes (7.5%) (p=0.004). Adiponectin levels are lowest in diabetic patients. After controlling for BMI, antipsychotic medication significantly influences adiponectin levels (p<0.01). Adiponectin levels are significantly lower (p<0.05) in patients treated with olanzapine.
Conclusion: In schizophrenic patients, adiponectin levels vary in the same
way as described in the normal, overweight and obese non schizophrenic
population. Also, adiponectin levels in schizophrenic patients with and
without metabolic syndrome mirror what is observed in the general
population. Preliminary data suggests that the antipsychotic treatment
may influence adiponectin regulation, a finding that should be verified in
longitudinal studies
S-28-04
Recommendations for monitoring and managing metabolic
disturbances during antipsychotic treatment
Dan Haupt
Washington University, School of Medicine, St. Louis, MO, USA
Introduction: Individuals with schizophrenia have elevated rates of mortality and medical comorbidity, related to increased rates of conditions
such as type 2 diabetes mellitus and cardiovascular disease. While it is
likely that lifestyle issues (e.g., reduced activity, poor nutrition) play a key
role, a range of evidence suggests that treatment with antipsychotic medications is associated with an increased risk for insulin resistance, hyperglycemia, and dyslipidemia. An American Diabetes Association (ADA)
Consensus Development Conference, co-sponsored by the American
Psychiatric Association (APA) and other organizations, recently addressed
this topic. Other international organizations have also published recommendations.
Method: The APA Committee on Research on Psychiatric Treatments
convened a workgroup to address outstanding questions and to provide
additional guidance to the field. Experts in endocrinology, cardiology, psychiatry and services research reviewed relevant literature in their respective areas of interest. Over 60 contributors submitted subsections for
review that are incorporated into the report, and over 80 participants
reviewed and edited the final report. Literature references were identified
primarily via Medline searches. The reports identified can be broadly divided
into 1) uncontrolled observational studies, 2) large, controlled, observational database analyses using prescription, administrative or - less commonly - population-based databases, and 3) controlled experimental
studies, including randomized clinical trials.
Results: On the specific topic of antipsychotics and diabetes or dyslipidemia risk, over 1000 papers are currently in the literature, with a more
limited literature of well-controlled experimental studies. The Workgroup
identified areas of consensus and discrepant results and/or discrepant
interpretations that will be incorporated into the final report.
Conclusion: Similar to the ADAs ongoing use of Consensus
Development Conferences, the APA Workgroup offers an opportunity to
address controversial areas of research with comprehensive expertise in
order to identify areas of consensus, discrepant results and directions for
future research. The APA workgroup identified opportunities for managing metabolic risk during antipsychotic treatment and improving health
outcomes.
48
S-33
Use of psychiatric drugs in the developing
world
S-33-01
The prescription pattern of neuroleptic in China
Tianmei Si
Peking University Insitute of Mental Health, Beijing, Peoples Republic of
China
China has a long history of traditional medicine, especially herbal medicine
and acupuncture. The modern era of treating psychotic disorders in China
began in 1950s. The earliest antipsychotic medication were rauwolfiae,
reserpine, promazine, and acetylpromazine. From early 1960s to late
1970s, these medications withdrew from the clinical practice. In 1956,
the domestic chlorpromazine was produced in Shanghai. Since then, the
typical drugs were gradually launched in the market. Beginning of the
1970s, domestic clozapine was developed in China, and used in the clinical practice till now without discontinuation. 10 provinces and cities
were selected according to the publishing CEIData of GDP(2000) by State
Statistics Bureau and the same sampling ratio of each economic level. The
investigation was conducted during 20th - 24th , May, 2002, using the
retested and revised self-made questionair. Second investigation was conducted during 23th-27th, may, 2006, using the same investigation tool.
The total number of sample was 4779 schizophrenia. the first 6 antipsychotic drugs used to treat the schizophrenia were clozapine, risperidone,
sulpride, chlorpromazine, perphenazine, and haloperidone, in turn. The
mean chlorpromazine equivalent dosage was (300 201)mg/d for the outpatients and (409 274) mg/d for the inpatients. 6.5% of the patients
were treated with antipsychotic depot. More than 2/3 patients were treated with monopharmacy. The second investigation entered 5857 schizophrenia. Data showed that the prescription pattern of neuroleptic in
China changes a lot. The second generation antipsychotic drugs are the
first line choice to treat the schizophrenia. More than 50% of the outpatients were treated with non-clozapine atypical antipsychotics, and about
one quarter of outpatients were treated with clozapine. Comparing with
4 years ago, the frequency of non-clozapine atypical antipsychotics
increases, and the useness of clozapine decreases. The factors related to
the prescription pattern changes include the new knowledge generalization, the changes of public concept to the mental disorders, medical system changes and novel medications availability, and so on. The use of psychotropic medication has the Chinese population-based characteristics.
References: 1. Kane J, Honigfeld G, Singer J, et al. Clozapine for the
treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine. Arch Gen Psychiatry, 1988, 45:789-796. 2. Chakos M,
Lieberman J, Hoffman E, et al. Effectiveness of second-generation antipsychotics in patients with treatment-resistant schizophrenia: a review and
meta-analysis of randomized trials. Am J Psychiatry, 2001, 158:518-526.
3. Kane JM, Marder SR, Schooler NR, et al. Clozapine and haloperidol in
moderately refractory schizophrenia: a 6-month randomized and doubleblind comparison. Arch Gen Psychiatry, 2001, 58:965-972. 4. Bhana N,
Foster RH, Olney R,et al. Olanzapine: an updated review of its use in the
management of schizophrenia. Drugs, 2001, 61:111-161. 5. Love RC,
Nelson MW. Pharmacology and clinical experience with risperidone.
Expert Opin Pharmacother, 2000, 1:1441-1453. 6. Feltus MS, Gardner
DM. Second generation antipsychotics for schizophrenia. Can J Clin
Pharmacol, 1999, 6:187-195. 7. Conley RR, Love RC, Kelly DL, et al.
Rehospitalization rates of patients recently discharged on a regimen of
risperidone or clozapine. Am J Psychiatry, 1999, 156:863-868.
S-33-02
Specific issues in the developing world: Hong Kong
Michael Wong
Queen Mary Hospital, Psychiatry, Hong Kong, Peoples Republic of
China: Hong Kong SAR
Introduction: The public psychiatric service in Hong Kong began to
develop in the 1950s. The drug budget was small which was mainly
based on the prescription of conventional antipsychotic and antidepressant. The expectation of patients and their carers has grown tremendously
in the past decade. There is growing demand for the prescription of
newer generation psychotropic medications which have improved side
effect profile and efficacy. This paper reviews the change of pattern of
prescription of antipsychotic and antidepressant medications in the past
decade in Hong Kong. The relationship of change in prescription pattern
and the increase of funding from the government was also studied.
Method: The precription of antipsychotic and antidepressant of all
patients who attended a psychiatric outpatient clinic of a regional general
hospital on a particular day in the last year was reviewed. The prescription
on the same day 5 and 10 years ago was also reviewed. The pattern of
prescription of antipsychotic and antidepressant medications was analyzed.
Results: There was changing pattern of the prescription of psychotropic
medications in the past decade. More newer generation medications
were available in the market and more patients were prescribed these
drugs. It also showed a relationship to the increase in funding from the
government.
Conclusion: The prescription of newer generation medications can be
influenced by the availability of the medications and the funding from the
government.
S-33-03
Specific issues in the developing world: India
E. Mohandas
India
Introduction: India, the largest democracy in the world with 1.09 billion
population has 0.4 psychiatrists/100000 population. Although India has
more than10000 pharmaceutical companies, it accounts for only 1-2% of
the global share. Almost all psychotropic agents marketed in developed
countries are available at affordable cost
Method: A review of the clinical practice guidelines and opinion survey
of psychiatrists
Results: National treatment guidelines are available, which are basically
imitated versions of the Western guidelines. Despite the thrust of
monotherapy or suggested practice guidelines, majority employ rational
polypharmacy. The current practice evolves around the use of conventional as well as newer generation antipsychotics. Tricyclic antidepressants
are still widely used even though newer generation antidepressants are
available. There is an upsurge in use of valproate in bipolar disorders.
There is growing trend in atypical antipsychotic augmentation apart from
lithium and thyroxine in difficult-to-treat depressives. ECT is a preferred
treatment modality.
Conclusion: The hither-to-available practice guidelines, the product of
wishful thinking considering the realities in a developing country, have to
be modified, as rational polypharmacy is so rampant
References: Mohandas E, Rajmohan V. Pharmacological Managment Of
Schizophrenia Indian Scene. Paper presented at: WAPR congress, Athens,
Greece. Oct 2006
Task Force on Clinical Practice Guidelines for
Psychiatrists in India. (2006) Clinical Practice Guidelines for Management
of Schizophrenia/ Mood disorders. Eds: S Gautam & A Avasthi, Indian
Psychiatric Society Publication
S-33-04
Specific issues in the developing world: Malaysia
Saroja Krishnaswamy
Penang Medical College, Department of Psychiatry, Malaysia
This talks relates the history of pharmocotherapy in Malaysia and discusses the current issues surrounding the advent of the newer psychotropics
in the last 2 to 3 decades.The pattern of drug use has changed and this
corresponds with the psychiatrisation of many stress related concerns.
Drug companies have in many ways capitalised on these trends and overtaken traditional modes of intervention including herbal and spiritual
means even for minor stress related ailments. The newer drugs like the
atypical antipsychotics, which have superior patient acceptabiliy also have
adverse effects , and many doctors are ill informed of this. The role of the
pharmaceutical industry in inflluencing therapeutic decisions is discussed
especially in newly emerging industrialised nations where in many places
the companies play a leading role in in educational activities in institution.
Some data on general drug itilisation versus alternative care is presented.
S-33-05
Psychiatric drugs used in Latin America. Mexicos case
Jose Luis Garcia-Aquirre
Mexico
Claudio Garcia-Barriga, Roberto Miranda-Camacho
Although in Mexico health care has been a constant point of concern,
attention has been mainly focused on infectious and chronic degenerating processes, neglecting mental health care most of the time; all this in
a country of 105 million people, even though predominately young,
showing signs of a sustained aging process according to the population
pyramid. According to the international disease classification, in its 10th
revision, 28.6% of the Mexican population presents some kind of disorder at least once in their lifetime; being affective disorders, Attention
deficit disorder, depression, and alcohol abuse the most common. Talking
about patients attention, for every 100 thousand inhabitants there exist
only 0.66 psychiatric beds, most of them located in psychiatric hospitals,
there are 2.7 psychiatrist, 0.1 psychiatric nurses, 1.2 neurologists and
0.2 social workers. Added to the insufficiency, there is a problem of distribution, due to the high concentration of professional in the mayor
cities. Also due to the insufficiency of specialized physicians, the use of
psychiatric drugs is limited. On the other hand there are the difficulties
incorporating the newly developed and highly efficient formulas to adequate treatment schemes, because of their high costs, which has forced
the implementation of new strategies as it is to incorporate the psychiatric drugs in to Social Security for formal workers and their families
which represent 55% of the total population; or the creation of the popular security program which will include psychiatric drugs, in order to
maintain the required doses and extent of the treatments. Amid these
strategies there is the creation, inside psychiatric hospitals, of Pharmacies
organized and managed by communitarian and support associations,
such as the Fray Bernardino Alvarez Psychiatric Hospital support committee pharmacy.
S-33-06
Specific issues in the developing world: South Africa
Soraya Seedat
MRC Unit on Anxiety & Stress, Disororder, Dept. of Psychiatry, Cape
Town, South Africa
Introduction: HIV/AIDS constitutes one of the biggest challenges to the
physical and mental health and to the social and economic development
of South Africans. Psychiatric disorders in HIV-infected individuals negatively impact disease prognosis, quality of life, antiretroviral (ARV) utilization and treatment adherence. They also increase the risk of becoming
infected, with relatively high rates of HIV noted in patients hospitalized
for mental illness. Over the past decade, the AIDS epidemic has had a
marked effect on mental health service provision in the country. Despite
ARVs being known to improve neurocognitive and functional performance in HIV-infected patients in sub-Saharan Africa, and arguably being
the single most effective intervention for some HIV-related mental disorders, measures to contain the epidemic in psychiatric hospitals in the
country have largely been inadequate. Furthermore, an integrated
approach to prevention and treatment of infected patients is lacking. One
big obstacle is the low ratio of mental health professionals, psychiatric
beds and services in proportion to the population. Additional barriers
include stigma and denial, very high rates of sexual and domestic violence
which have increased the spread of HIV among young women, lack of
49
political will and commitment, and the cost of treatment and access to
care. This presentation will discuss the status quo regarding use of psychotropic medications and ARVs in HIV-infected patients in state psychiatric facilities in South Africa.
S-33-07
Utilization patterns of antipsychotic agents in psychiatric
inpatients in Taiwan: An analysis of the medical claim
dataset Taiwan
El-Wui Loh
Taiwan
Sur-Fen Susan Gau, Keh-Ming Lin
Introduction: During early 1990s, typical antipsychotics were still the
major prescribed therapeutics for schizophrenic patients around the
world, including Taiwan. Atypical antipsychotics that are less likely to
cause extra-pyramidal symptoms have generated obvious changes of
antipsychotic prescriptions since their introduction. In Taiwan, the
changes might have been slowed down by the health policy and regulations of the National Health Insurance of the time which discouraged the
use of atypicals. This limitation was removed later. To examine the
changes of the utilization pattern of antipsychotics in Taiwan, we analyzed the Psychiatric Inpatient Medical Claim Dataset (PIMC) of National
Health Insurance Research Database, Taiwan.
Method: Patients hospitalized during 1996 to 2001 with a diagnosis of
ICD-9-CM 290 to 319 or A-code of A210 to A219, were identified and
medical claim records during1996 to 2003 retrieved. Un-valid data were
removed and trend tests were used to analyze the utilization patterns of
antipsychotics.
Results: Number of patients using typical antipsychotics significantly
decreased from 97% to 82% during 1997 to 2001, while that of atypicals increased from 3.4% to 28.8%. Further analyses on major antipsychotics prescribed, i.e., depot antipsychotics for typicals and clozapine for
atypicals, demonstrated significant decrement from 36% to 23.3% and
increment from 7.9% to 15%. The utilization patterns of typical and
atypical antipsychotics persisted and similar (1) between general and
mental hospitals and (2) among medical, regional and area hospitals.
Conclusion: In Taiwan, prescriptions of typical antipsychotics during
1997 to 2001 decreased significantly while those of atypicals increased,
although the speed of changes was slower than western countries.
However, whether such changes imply a better health for schizophrenic
patients is still to be investigated. Coming findings on disease etiology,
new development in pharmacology and possible introduction of pharmacogenetics into clinical practice may have further impacts on the patterns
of use and this should be monitored.
S-46
A role of glutamate receptors in mood disorders
S-46-01
The role of group I mGlu receptors in mood disorders
Gabriel Nowak
Institute of Pharmacology, Dept. Neurobiology, Krakow, Poland
Andrzej Pilc
Introduction: There is considerable evidence to indicate the involvement
of glutamate in the pathophysiology and treatment of affective disorders
(depression). The pioneering studies with NMDA/glutamate antagonists
opened glutamate-depression research avenue. Besides ionotropic, also
metabotropic Glu receptors seem to participate in the mechanism of antidepressants.
Results: Preclinical studies indicate that antagonists of group I mGlu
receptors demonstrate antidepressant-like activity. Compounds: MPEP,
MTEP, AIDA are effective in forced swim/tail suspension tests or olfactory
bulbectomy animal model of depression. Moreover, zinc, non-specific
antagonist of group I mGlu and NMDA receptors, exhibits antidepressant
50
activity in forced swim/tail suspension tests and animal models of depression (olfactory bulbectomy, chronic unpredictable stress, chronic mild
stress). Chronic treatment with MPEP, MTEP or zinc induced adaptation in
BDNF gene expression and adrenergic (-1, -1) receptors, similar to that
changes induced by most antidepressants.
Conclusion: All the preclinical data together with very limited clinical
reports indicate that possible antidepressant benefits might come from
reduction of the function of group I mGlu receptors.
S-46-02
NMDA receptors: A target of antidepressant action
Phil Skolnick
DOV Pharmaceutical, Discovery, Somerset, NJ, USA
Introduction: Converging lines of evidence indicate that dampening
NMDA receptor function can result in an antidepressant-like action
[reviewed in 1]. For example, NMDA antagonists exhibit antidepressantlike properties in preclinical procedures (such as the forced swim test, tail
suspension test, and chronic mild stress model) predictive of antidepressant action. Further, chronic treatment with a diverse group of biogenicamine based antidepressants has been reported to dampen NMDA receptor function as evinced by biochemical, molecular, electrophysiological
and behavioral techniques. These latter findings have led to the hypothesis [1] that NMDA receptors represent one of the downstream targets of
conventional antidepressants. A corollary of this hypothesis is that this
dampening of NMDA receptor function produced by biogenic-amine
based antidepressants contributes to the therapeutic lag (the >2-3
weeks of treatment required to produce meaningful symptom relief) characteristic of these agents. If this hypothesis is correct, then NMDA antagonists may provide a more rapid onset of action and perhaps greater
efficacy than biogenic-amine based agents. Such preclinical findings have
catalyzed clinical trials with NMDA antagonists in depressed individuals. A
recent [2] double-blind, placebo controlled study demonstrated a very
rapid and robust antidepressant action of the NMDA receptor antagonist,
ketamine. This study extended and confirmed an earlier, more modest
open label study conducted with ketamine in depressed individuals [3]. In
this presentation, I will review preclinical and clinical findings that NMDA
antagonists are antidepressant, and that chronic treatment with conventional antidepressants dampens or attenuates NMDA receptor function.
References: 1. Skolnick, P. Eur. J. Pharmacol. 375: 31-40, 1999. 2.
Zarate, C., et al. Arch. Gen. Psychiatry 63:856-64, 2006. 3. Berman, R.,
et al. Biol. Psychiatry 47:351-4, 2000.
S-46-03
The role of AMPA receptors in depression and antidepressant drug action
Jeffrey Witkin
Introduction: Although the monoamine hypothesis of depression
remains a cornerstone of our understanding of the pathophysiology of
depression, emerging data has suggested that the alpha-amino-3hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subtype of
glutamate receptor may also play a pivotal role in depression. Positive
allosteric modulators of AMPA receptors increase brain levels of brainderived neurotrophic factor (BDNF) that impacts the viability and generation of neurons in key brain structures.
Method: The present talk will summarize the data in the biochemical,
behavioral and neurobiological literature that links AMPA receptor function to mood disorders (see Alt et al., 2006 for overview).
Results: The evidence supporting the idea that AMPA receptors are a key
transduction link in the control of mood disorders is as follows: 1) AMPA
receptors are modified in brains of depressed patients, 2) AMPA receptor
potentiator molecules have antidepressant-like biochemical and behavioral effects in rodents, 3) the antidepressant fluoxetine alters the phosphorylation of GluR1 in a manner predicted to amplify AMPA receptor
function, and 4) Other potential antidepressants such as mGlu2/3 antagonists also appear to produce their effects in vivo via potentiation of
AMPA receptors.
Conclusion: AMPA receptor potentiation might be a general mechanism

through which the clinical outcome of antidepressant efficacy is achieved.
Small molecule potentiators of AMPA receptors have been discovered and
are in development for cognition and depression.
References: Alt, A., Nisenbaum E. S., Bleakman D. and Witkin, J. M. A
role for AMPA receptors in mood disorders. Biochemical Pharmacology
71:1273-1288, 2006.
S-46-04
Antidepressant effects of mGlu2/3 receptor antagonists
Shigeyuki Chaki
Taisho Pharmaceutical Co., Med Pharmacol Lab, Saitama, Japan
Introduction: Glutamatergic abnormalities are involved in several
psychiatric disorders. Glutamate acts at two classes of receptors,
ionotropic and metabotropic glutamate (mGlu) receptors, and latter has
eight subtypes (mGlu1-mGlu8). Among them, recent pharmacological
and histochemical studies suggest mGlu2/3 receptor has crucial roles in
the control of emotional states, and is implicated in the pathology of psychiatric disorders such as depression and anxiety. Therefore, we have
investigated the effects of mGlu2/3 receptor antagonists (MGS0039 and
LY341495) in animal models of depression.
Method: Antidepressant effects were evaluated in the forced swimming
test, tail suspension test and learned helplessness paradigm. Effects on
monoaminergic transmissions were investigated by microdialysis and electrophysiological studies. Effect on progenitor cell proliferation was investigated by immunohistochemical analyses after BrdU injection.
Results: Both MGS0039 and LY341495 reduced immobility in the forced
swimming test and tail suspension test, indicating antidepressant effects.
The antidepressant effect of MGS0039 in the tail suspension test was
partly attenuated by an AMPA receptor antagonist. Sub-chronic administration of MGS0039 for 7 days produced a significant antidepressant
effect in the learned helplessness paradigm. MGS0039 significantly
increased firing rate of the dorsal raphe nucleus serotonin neurons, serotonin release in the medial prefrontal cortex, and dopamine release in the
nucleus accumbens shell, indicating that MGS0039 enhanced serotonergic and dopaminergic transmissions. Moreover, sub-chronic administration of MGS0039 significantly increased progenitor cell proliferation in
the dentate gyrus in the hippocampus.
Conclusion: These results suggest that blockade of mGlu2/3 receptor
produces antidepressant effects in rodents, and mGlu2/3 receptor antagonists may represent a novel approach for the treatment of depression.
Although precise neuronal mechanisms underlying antidepressant effects
of mGlu2/3 receptor antagonists remain to be elucidated, increased serotonergic and accumbal dopaminergic transmissions, increase in hippocampal neurogenesis and potentiation of AMPA receptor may mediate
the antidepressant effects of mGlu2/3 receptor antagonists.
51
OTHER - Symposia
S-16
Current and future perspectives on Transcranial
Magnetic Stimulation (TMS) in psychiatric clinical practice
T12 Other
S-16-01
Neurophysiological bases of the efficacy of transcranial
magnetic stimulation in psychiatric disorders
Anastasios Konstantinidis
University of Vienna, Dept. for General Psychiatry, Austria
S. Kasper
Transcranial magnetic stimulation (TMS) was first introduced by Barker et
al. as a neurophysiological investigational method to study brain-behavior
relationships. In the course of time TMS was investigated in almost all
areas of cognitive neuroscience demonstrating putative effects in a number of psychiatric disorders. Due to the difficulty of evaluating the impact
of the induced magnetic field on brain systems and the still unknown
pathophysiology of most psychiatric disorders, the neurophysiological
mechanisms underlying TMS-induced changes in mood and behavior are
still for the most part unknown. TMS may be delivered as a single pulse,
in paired pulses, or as repetitive trains of stimulation (rTMS) inducing
regarding to stimulation frequency inhibition or excitation of the neural
circuitry. The basic mechanism of action is based on generating a focused
electrical stimulation which reaches unimpeded through scalp and cranium the underlying tissue inducing neuron-depolarization. Data supports
a possible antidepressant mode of action through modulation of circadian rhythms. Furthermore a triggering of dopamine release has been
implied using PET-scanning and 11C raclopride binding on dopamine
receptors of the prefrontal cortex regions. Although inconclusive several
studies documented effects of rTMS on plasma levels of cortisol, prolactin
and thyroid stimulating hormone indicating a mode of action through
alteration of the neuroendocrine function. The implementation of imaging techniques showed TMS as biologically active, both locally in tissue
under the coil and at remote sites, presumably through transynaptic
connections. Furthermore rTMS is able to increase the expression and
release of potential neuroprotective substances showing herewith a
potential in the treatment of neurodegenerative diseases. In conclusion
further studies to illuminate the possible neurophysiological mechanisms
underlying the therapeutic effects are needed.
References: Schlaepfer T.E., et al. Efficacy of repetitive transcranial magnetic stimulation (rTMS) in the treatment pf affective disorders. 2003,
Neuropsychoph 28, 201-205. Post M., Keck M.E. Transcranial magnetic
stimulation as a therapeutic tool in psychiatry: what do we know about
the neurobiological mechanisms? 2001, J Psychiatr Res 35, 193-215.
S-16-02
TMS-EEG measures of excitability and connectivity of the
human cerebral cortex: Possible applications in psychiatry
Mario Rosanova
University of Milan, DISC, Italy
Valentina Bellina, Federico Resta, Maurizio Mariotti, Marcello Massimini
Introduction: Several psychiatric disorders have been correlated with
anomalous activity and connectivity of different areas of the cerebral cortex. The combination of transcranial magnetic stimulation and high density electroencephalography (TMS/hd-EEG) allows direct, noninvasive
measure of the excitability and the connectivity of any cortical area. TMSevoked potentials (TMSEPs) may represent a new tool to study cortical circuits in psychiatric patients; however, their basic properties in health and
disease are still largely unknown. In this study we asked to what extent
TMSEPs are (1) specific for the stimulated site (2) reproducible over time
(3) changing in psychiatric patients.
Method: Using an MRI-guided infrared positioning system, we targeted
4 cortical areas (4, 6, 18 and 19) in each subject (n=5). We stimulated all
areas at 3 different intensities (100V/m, 130V/m and 160V/m on the cor-
52
tical surface). The EEG response was recorded using a TMS compatible,
60-channels amplifier. Traditional averaging procedures were used to calculate scalp potentials and cortical current density.
Results: TMSEPs waveforms from different areas displayed common features: initial fast (20-30 Hz) waves until 150 ms, followed by slower (5-10
Hz) components that lasted until about 300 ms. Voltage and current distributions of fast waves were highly specific for the stimulated site, indicating the recurrent engagement of a discrete cortico-cortical and cortico-thalamo-cortical modules. Higher stimulation intensities resulted in
increased amplitudes and latencies of fast waves. Targeting the same cortical site, a week later in the same subject, resulted in overlapping waveforms, voltage and current distributions.
Conclusion: These results indicate that TMSEPs: (1) reflect the excitability
and the connectivity of specific modules of the human thalamocortical
system, (2) are highly reproducible over time. Preliminary data about the
TMSEPs from prefrontal areas in depressed patients suggest the potential
research and clinical applications of TMS/hd-EEG in psychiatry.
S-16-03
Transcranial magnetic stimulation treatment of resistant
bipolar depression
Carlo Altamura
University of Milan, Dept. of Psychiatry, Italy
Bernardo DellOsso, S. Pozzoli, M.F. E. Bosi, M. Rosanova, M. Buoli, M.
Mariotti
Repetitive Transcranial Magnetic Stimulation (rTMS) of the Dorsolateral
Prefrontal Cortex (DLPFC) has shown some efficacy in patients with treatment-resistant depression either at low or high frequency1. The efficacy
of rTMS, however, has been mainly investigated in unipolar depression
and, only recently, in bipolar depressed patients2. A recent study reported prefrontal rTMS as safe and effective, although the effectiveness did
not reach statistical significance in a group of bipolar depressed patients2.
Moreover, another study showed that rTMS may be helpful as maintenance treatment for Bipolar Depression3. Throughout the presentation,
the state of the art of the use of TMS in Bipolar Depression will be critically discussed along with the results from an original study on bipolar
depressed patients performed at the Affective Disorders Unit (within the
University Department of Psychiatry of Milan). The study consisted of
three weeks of low-frequency (1Hz) rTMS combined to brain navigation
through a previous Magnetic Nuclear Resonance (RMN), administered to
10 patients with a diagnosis of Bipolar Disorder, either type I or II and a
Major Depressive Episode. To be enrolled in the study, patients had shown
partial or no response to antidepressants and, during TMS treatment, they
were maintained on the same treatment including antidepressants and
divalproex at fixed doses.
References: 1. Lisanby S.H., Kinnunen L.H., Crupain M.J. Applications of
TMS to therapy in psychiatry, J Clin Neurophysiol., 2002; 19: 344-60
2.Nahas Z., Kozel F.A., Li X., George M.S. Left prefrontal transcranial magnetic stimulation (TMS) treatment of depression in bipolar affective disorder: a pilot study of acute safety and efficacy. Bipolar Disord, 2003; 5:
40-7. 3. Li X, Nahas Z, Anderson B, Kozel FA, George MS. Can left prefrontal rTMS be used as a maintenance treatment for bipolar depression?
Depress Anxiety, 2004; 20: 98-100.
S-16-04
Comparison of TMS with ECT
Marco Antonio Marcolin
Sao Paulo, Brazil
Introduction: Repetitive transcranial magnetic stimulation (rTMS) can
induce significant antidepressant effects and might be an alternative to
electroconvulsive therapy (ECT). Although several studies have compared
the efficacy of rTMS and ECT, the results of these studies are mixed and
therefore the comparison of these two therapies needs to be further
explored.
OTHER - Symposia
Method: Randomized, single-blinded controlled trial comparing rTMS

and ECT. Forty-two patients between 18 to 65 years old, referred to ECT
due to unipolar non-psychotic depression refractoriness were offered to
enter the study. Patients received either rTMS (20 sessions, intensity of
100% of motor threshold, 10Hz, 2500 pulses per session) or ECT (6 to 12
sessions, right unilateral or bilateral ECT).
Results: There was no difference in the antidepressant efficacy of ECT
and rTMS as evaluated by a single blinded rater - the response rates were
relatively high in both groups (40% and 50%, respectively), with no significant difference between them (p=0.55) in an intent to treat analysis.
There was also no significant difference in the neuropsychological test
performance after either one of these therapies.
Conclusion: Both treatments were associated with a significant improvement in depression in a population with severe refractory depression and
therefore add to the literature that rTMS can be an effective substitute for
ECT as it is a less costly treatment and it is not associated with anesthetic
and other ECT risks.
References: Rosa MA, Gattaz WF, Pascual-Leone A, Fregni F, Rosa MO,
Rumi DO, Myczkowski M, Silva MF, Mansur C, Rigonatti SP, Jacobsen
Teixeira M, Marcolin MA. Comparison of repetitive transcranial magnetic
stimulation and electroconvulsive therapy in unipolar non-psychotic
refractory depression: a randomized, single-blind study. Int J
Neuropsychopharmacol. 2006 Dec;9(6):667-76
S-18
Treatment of sexual offending
T12 Other
S-18-01
H. Gordon
Oxford, United Kingdom
S-18-02
Antiandrogen treatment: Which indications?
Florence Thibaut
University Hospital Ch Nicolle, INSERM U 614, Rouen, France
Pharmacological treatment of sexually deviant behavior had historically
been based on studies that involved the surgical castration of sex offenders.
The assumption is that suppression of the sexual drive would decrease
paraphilic sexual behaviour. Ideally, successful treatment would mean that
deviant sexual behaviours were suppressed, while conventional sexual
fantasies and urges would be maintained or enhanced. Antiandrogen
treatments, which either drastically lower testosterone levels or antagonize the action of testosterone at the receptor level, have been used alone
or in conjunction with other treatment modalities. The efficacy of cyproterone acetate or GnRH analogs/agonists, which constitute promising
treatments for some sex offenders, will be reviewed.
S-18-03
Ethics of coerced treatment of sex offenders
Paul Cosyns
University Hospital Anwerp, Dept. of Psychiatry, Antwerpen, Belgium
Introduction: In case of involuntary judicial treatment of sex offenders,
the judicial coercer is a third party in the therapeutic relation. There is
even a fourth party that cannot be denied by the therapist, the past victims and potential new ones.
Method: We will focus on the main ethical issues of involuntary treatment:
How can involuntary treatment comply with the informed consent rule?
What about the criterion of dangerousness and risk of violence?
The principles of the least restrictive alternative.
Results: The ethical justification for involuntary treatment are:
The treatment redresses competence in incompetent patients
The treatment reduces the risk of violence toward third parties.
The patient benefits from the treatment or lack of treatment will be
detrimental for his mental health.
Conclusion: We will propose an ethical framework for the use of hormonal therapy (hormonal castration) to reduce the sex drive of paraphilic
patients.
S-18-04
Antidepressant treatment for the consequences of sexual
abuse
Flora de la Barra
University of Chile, Psychiatry, Santiago, Chile
Introduction: The existing evidence for the treatment of sexual offending with SSRIs is reviewed. The rationale for SSRI treatment is based on
the existence of underlying and comorbid psychiatric disorders, certain
similarities between paraphilias and obsessive/ compulsive disorders, and
association to brain monamine disregulation.
Method: A bibliographic search was made on Medline & Pubmed, internet and letters to authors. The following descriptors were used:
Antidepressants, sexual offenders. Papers were analyzed critically, to
assess current state of research.
Results: Controversy exists between clinicians that propose SSRI treatment only for patients with obsessive compulsive symptoms and others
that recommend it for paraphilic and not paraphilic sexual offenders. In
a recent specific meta-analysis of cost/ effectiveness of SSRIs in the treatment of sexual offenders, no RCT studies were found, a qualitative analysis was done of cohort and case studies. 9 studies were finally included
(Perilstein 91, Stein 92, Kafka 92, 94, 2000, Coleman 92, Bradford 95,
Fedoroff 95, Greenberg 96). 8 showed improvement in a wide range of
measures. Additional costs were due to the cost of the drugs.
Conclusion: All the clinicians treating sexual offenders agree that SSRIs
offer a promising alternative for some patients, within a broader treatment program. Researchers on the other hand, state that there is an
urgent need for blind randomized controlled studies.
References: -Adi Y, Ashcroft D, Browne K et als. Clinical effectiveness
and cost-consequences od selective serotonin reuptake inhibitors in the
treatment of sex offenders. Health Tcchnol Assess 2002; 6(28) -Kafka M.
The monoamine hypothesis for the pathophysiology of paraphilic disorders: an update. Ann.N.Y. Acad.Sci. 2003; 989: 86-94 -Hill A, Briken P,
Kraus C et als. International Journal of Offender Therapy and
Comparative Criminology 2003, 47: 4 , 407-421. -Bradford. The
Neurobiology, Neuropharmacology and Pharmacological Treatment of the
Paraphilias and Compulsive Sexual behavior.Can J Psychiatry 2001, 46;
26-34.
S-22
Rating scales in mental health: From research
into the clinical arena
T12 Other
S-22-01
Brief overview on the use of rating scales in research and
clinical practice
Martha Sajatovic
Case Western Reserve Univ., School of Medicine, Cleveland, Ohio, USA
Rating scales are useful tools to measure a variety of components of mental health including symptoms, disability, level of functioning, quality of
life and interpersonal relationships. Rating scales can be used to make a
diagnosis as well as to evaluate a disease state at a given moment.
Additionally, rating scales can be quite valuable in assisting with prognostic assessments and to measure outcomes of treatment. Rating scales are
often used in research settings, however many types of rating scales can
be easily used in clinical settings, where they can provide useful information. Steps to the successful use of mental health rating scales include
being familiar with the scale in question, using supporting information as
appropriate and performing a thorough and complete interview. There
are a variety of types of rating scales including diagnostic scales, symptom-based scales, diagnosis-specific scales, self-rated and interviewerrated scales as well that scales that measure a multitude of dimensions of
outcome. Use of rating scales in clinical practice may focus attention on
target symptoms or areas of clinical concern, and thus have implications with respect to psychoeducation, treatment adherence and treatment outcomes
53
OTHER - Symposia
S-22-02
Rating scales in psychotic conditions: From clinical anecdote to medical experience
Veronica Larach-Walters
Psychiatry, Santiago, Chile
Usual practice till not long ago considered not feasible or useful for everyday practice the use of rating scales, especially outside of research formal
settings. This presentation will review the organization of regular clinical
practice with the use of scales, in an outpatient clinic for psychotic
patients in a large hospital from its very beginning in 1979, with a depot
program to begin with and after with an atypical antipsychotic treatment
program. Scales were applied on regular visits for psychopathology,
adverse events, nurse observations, symptom checklists, global improvement and overall severity. We will discuss the advantages of this methodology for clinical practice that yielded both measurements on clinical outcomes and also for cost- effectiveness appraisals, plus possibilities of standardizing procedures and improving treatment strategies and the development of training and research.
S-22-03
Rating scales in mood disorders and anxiety disorders
Luis Ramirez
St. Vincent Charity Hospital, Psychiatry, Cleveland, USA
The scales utilized to assess mood and anxiety disorders can be classified
according to their function. For example: A.- Diagnostic scales are assessment tools that identify specific mental disorders. These scales are lengthy
and are basically utilized in research activities. Some of them are the
Present State Examination (PSE) and the Structured Clinical Interview for
Axis I DSM Disorders (SCID)B.- Symptom-based scales are based on the
assessment of a particular symptom or symptoms and are not targeted to
a specific diagnosis. The classic example in this classification is the Brief
Psychiatric Rating Scale (BPRS)C.- Diagnosis-specific scales highly utilized
in clinical research and in clinical activities in general. They are designed
to be used to assess patients with specific diagnosis like the Hamilton
Scale for Depression an the Hamilton Scale for Anxiety. Another classification to be considered is the one looking at the scales as self-rated
-vs- rater-administered scales. One of the best known self-rated scales is
the Beck Depression Inventory.During the presentation other scales to
evaluate depression and anxiety will be discussed.
S-22-04
Rating scales in child population
Roxana B. Galeno
Directora Instituto, Neurociencias, Mendoza, Argentina
Recently, several techniques for comprehensive evaluation have been
developed like diagnostic instruments and rating scales which measure
the variety and severity of symptoms in mental disorders in child and adolescents.The need for quantitative clinical evaluation tools to use in child
psychiatry is obvious. Structured Interviews and rating scales are useful for
comparing clinical and laboratory data, monitoring the effects of treatments, and enhancing communication between clinicians and investigators. The methodological principles used to construct and validate such
tools will be described. This approach is of benefit in most psychiatric disorders of children and adolescents. The questionnaires and scales most
widely used throughout the world will be reviewed. The advantages and
drawbacks of evaluation scales in everyday practice and in research will
be discussed. But it is very important to keep in mind that the instruments
that will be described can help identify a variety of symptoms affecting
children and adolescents. Do not assume that a particular score on any
rating scale or screening tool means a child has a particular disorder;
these instruments are only one component of an evaluation. Diagnoses
should be made only by a trained clinician after a thorough assessment.
54
S-30
Do latest research topics change our understanding of personality disorders?
T12 Other
S-30-01
Ten-year course of borderline personality disorder
Mary Zanarini
McLean Hospital, Belmont, MO, USA
Introduction: One purpose of this study was to assess the symptomatic
and functional course of a sample of carefully diagnosed patients with
borderline personality disorder (BPD) followed prospectively for 10 years.
Another purpose was to determine the best predictors of time to remission from BPD.
Method: The symptomatic and functional status of 362 former inpatients
participating in the McLean Study of Adult Development (MSAD) was
assessed every two years using semistructured interviews of demonstrated
reliability. 290 met both DIB-R and DSM-III-R criteria for BPD and 72 others
met DSM-III-R criteria for another axis II disorder (and neither criteria set
for BPD). 92% of the surviving borderline patients and 85% of the surviving axis II comparison subjects were reinterviewed at all five follow-up
waves.
Results: All told, 88% of the 275 patients with BPD reinterviewed at least
once experienced a remission of their BPD and 79% attained good psychosocial functioning. Recurrences of BPD and suicide were relatively rare:
18% and 4%, respectively. It was also found that some symptoms (e.g.,
self-mutilation, quasi psychotic thought) resolve relatively quickly and are
acute in nature, while other symptoms (e.g., intense anger, serious abandonment concerns) resolve relatively slowly and are temperamental in
nature. In addition, findings pertaining to a clinically meaningful set of
baseline predictors of time to remission will be presented.
Conclusion: The results of this study suggest that both symptomatic
remission and the attainment of a good level of psychosocial functioning
are common among even the most disturbed patients with BPD. These
results also suggest a more hopeful prognosis for BPD than previously
recognized.
S-30-02
Is there a common neuroanatomy underlying BPD symptoms?
Christian Schmahl
Central Institute of Mental Health, Psychosomatic Medicine, Mannheim,
Germany
Introduction: Structural and functional neuroimaging in borderline personality disorder (BPD) has revealed a dysfunctional network of brain regions that seem to mediate much, if not all of the BPD symptomatology.
Methods: This frontolimbic network consists of anterior cingulate cortex,
orbitofrontal and dorsolateral prefrontal cortex, hippocampus, and amygdala. FDG-PET studies have revealed altered baseline metabolism in prefrontal regions including ACC. Challenge studies using emotional, stressful, and sensory stimuli have consistently shown deactivation or failure of
activation of ACC in patients with BPD.
Results: ACC may be viewed as a brain region mediating affective control, and dysfunction in this area could be related to affective dysregulation which is characteristic of BPD.
Conclusion: Deactivation in ACC and amygdala could also be demonstated to be related to reduced pain perception in these patients.
OTHER - Symposia
S-30-03
Neurobiology of antisocial disorders
Sabine Herpertz
Rostock University, Psychiatry and Psychotherapy, Germany
B. Herpertz-Dahlmann
Introduction: Aggressive behavior in mental disorders may occur in
childhood in the context of conduct disorder or in adulthood as a leading
feature of personality disorders, psychopathic or borderline personality
disorder, in particular. Those children, who meet the criteria for conduct
disorder already in early life (early starters) tend to exhibit high levels of
aggression throughout development and continuation of violence in
adulthood. There are several lines of evidence that aggressive behavior at
any age is closely related to an individuals capability to regulate emotions.
Emotions of anger or fear trigger reactive, impulsive aggression whereas
a failure to experience fear, empathy or guilt facilitates instrumental
aggression.
Methods: A functional neuroimaging design was applied to study the
processing of emotional stimuli in boys with early-onset conduct disorder.
Functional magnetic resonance imaging data were analyzed in 22 male
adolescents aged 12 to 17 years with childhood-onset CD (16 of them
with co-morbid ADHD) compared to 22 age-matched male healthy controls. For functional data, pictures of either negative, positive or neutral
valence were presented in a passive viewing task.
Results: When comparing CD patients with healthy controls, we found
enhanced left-sided amygdala activation in response to negative compared to neutral pictures in the patient group. In addition, analyses
suggested that CD boys showed increased activation in the orbitofrontal,
rostral anterior cingulate and insular cortices. In response to positive
pictures no significant group effect was found.
Conclusion: Conclusions: The findings provide a neurobiological basis for
the notion that CD is closely related to dysregulated emotions. Further
studies should clarify whether the increased activation in fronto-limbic
networks resembles hyperresponsivity found in impulsive, emotionalunstable personalities or reflects a compensatory mechanism discussed
for callous, psychopathic individuals. In psychopaths, reduced amygdala
functioning has been hypothesized to be the most significant biological
factor underlying emotional detachment and instrumental aggression.
However, although psychopaths show considerable evidence of amygdala dysfunction, the direction of change is inconsistent with the majority of
studies showing reduced, but others increased amygdala activation.
References: work submitted
S-30-04
The pathophysiology of the schizophrenic disorders:
Perspective from the spectrum
Larry Siever
Mount Sinai School of Medicine, Psychiatry, New York, USA
Introduction: Schizotypal personality disorder (SPD) is closely related to
schizophrenia from pharmacologic, genetic, and neurobiologic perspectives. SPD patients shared cognitive impairment with schizophrenic
patients with deficits in prefrontal activation during cognitive tasks based
on reduced dopaminergic activity at D1 receptors. Both noradrenergic
activation of alpha2-adrenergic receptors and dopaminergic activation of
D1 receptors can increase efficiency of prefrontal cortical processing. The
pathophysiology of SPD and schizophrenia will be presented with our latest research study evaluating dopaminergic and noradrenergic interventions in SPD.
Method: 24 SPD and 20 OPD patients entered a double-blind placebo
controlled treatment trial and received guanfacine, an alpha2-adrenergic
agonist, at a dose at 2 mg/day over four weeks. 16 SPD patients entered
a double blind placebo controlled trial of pergolide, a mixed D1/D2 agonist, treatment; 10 received pergolide up to a maximum of .1 mg/wk over
four weeks.
Results: Guanfacine had significant beneficial effects on several cognitive
domains including substantial effects on maintenance working memory
measured by the DOT test of visuospatial working memory. Guanfacine
treatment in SPD subjects reduced long delayed BX errors (p<0.05,
covarying for baseline) and increased long delay AY errors. Pergolide
resulted in a significant decrease in BX errors (F(1, 16) = 6.62, p = .02)

reflecting an almost one third decrease in BX errors and a significant
increase in AY errors was observed as well. Preliminary results suggest
that D1 receptors in the schizophrenia spectrum may be increased in subcortical regions in schizotypal subjects with relative reductions in binding
associated with greater anhedonia (p < .05).
Conclusion: Both guanfacine and pergolide improved working memory
and reliance on context. Pergolide had a greater effect on an auditory
working memory task and guanfacine on a delay-dependent visuospatial
working memory task. These results will be discussed in terms of a model
of pathophysiology of SPD.
S-32
The transnosographic aspects of anhedonia:
From psychopathology to treatment
T12 Other
S-32-01
Anhedonia in contemporary classification systems
Michael Musalek
Anton Proksch Institute, Vienna, Austria
Summarizing the various publications on the nosological position, anhedonia is a nosological non-specific syndrome which may occur in the
course of all psychiatric disorders and illnesses. According to the results of
our psychopathological analyses, the pathogenesis of anhedonia has to
be considered as a multidimensional circular process in which various
mental, physical and social factors act as predisposing, triggering and disorder-maintaining factors. Stressors induced by particular experiences and
perceptions and by impaired health may lead to a state of anhedonia if
adequate coping mechanisms are missing. Anhedonia itself usually leads
to a deterioration in the mental and physical state of the patient, and
shows a clear impact on the patients social network. The reactions of
people close to the patient combined with the impaired mental and physical conditions of the patient cause the circle to restart. As contemporary
diagnostic entities do not refer to pathogenesis, classical categorical diagnostics cannot provide the basis for effective pathogenesis-oriented therapy. A change of paradigm in diagnostics from a categorical to a dimensional approach thus becomes necessary. Following a dimensional diagnostic approach based on a dynamic model of vulnerability, a precise differential diagnosis of the complex constellation of conditions and their
interactions becomes necessary in order to develop effective treatment
strategies. Disorder-maintaining factors determine the treatment of the
acute symptomatology, whereas predisposing and triggering factors serve
as the basis for the prophylactic treatment.
S-32-02
Exaggerated emotional responses following withdrawal
from hypnotic-sedative drugs or stress are associated with
the lack of feed-back inhibition on rat basolateral amygdala
Victor A. Molina
Univ. Nacional de Cordoba, Dept. de Farmacologia, Argentina
Numerous studies provide evidence that experiencing relevant threatening situations leads to subsequent exaggerated emotional responses and
anhedonia. Also, the emergence of a negative emotional state - characterized by distress, disphoria, anhedonia, anxiety and other exaggerated
emotional reactions - is a common behavioral output following the
abrupt abstinence from diverse drugs of abuse, providing a powerful
motivational factor to relapse after discontinuation of drug administration. It is known that the amygdala plays a major role in the generation
of such negative affective states. In this report we demonstrated that discontinuation from chronic ethanol (ETOH) and benzodiazepine (BDZ)
administration facilitated the formation of a new fear memory concomitant with a marked resistance to being extinguished. Similarly, previous
exposure to an uncontrollable stressor increased fear memory. In addition,
the infusion of bicuculline, a competitive antagonist of GABAA receptors,
55
OTHER - Symposia
into the basolateral amygdala complex (BLA), but not into the central
amygdaloid nucleus, induced the same behavioral effect. Pretreatment
with midazolam (MDZ) prevented the facilitating influence on fear memory of stress. Evoked potentials were studied in BLA slices from stressed
or withdrawn animals. Potentials evoked in the BLA by single stimuli
applied to the external capsule showed multispike responses, suggestive
of GABAergic disinhibition in BLA. Long-term potentiation (LTP) was
induced with a single train of high-frequency stimulation, which did not
induce LTP in control rats. Therefore, stress and withdrawal attenuates
inhibitory GABAergic control in the BLA, leading to neuronal hyperexcitability and increased plasticity that facilitates fear learning. In slices containing the BLA, inhibitory postsynaptic potentials (IPSPs) were studied
using whole cell patch-clamp. In control animals, a small picrotoxin-sensitive IPSP was evoked by sub threshold stimulation of cortical afferents
contained in the external capsule. When an action potential (AP) was
evoked by supra threshold stimuli, the IPSPs were considerably larger. It is
concluded that a history of severe stress or withdrawal to hypnotic-sedative drugs results in the suppression of feed-back inhibition in BLA projection neurons, which represents an essential mechanism underlying the
emergence of a negative emotional state, including exaggerated fear and
anxiety.
S-32-03
Anhedonia in substance use disorders
Luigi Janiri
Catholic University, Rome, Italy
Anhedonia is a condition in which the capacity of experiencing pleasure
is totally or partially lost, frequently occurring in mood disorders, as a
negative symptom in schizophrenia, and in substance use disorders. As to
drug dependence, anhedonia was found to be a frequent feature in alcoholics and addicted patients during acute and chronic withdrawal, as well
as in cocaine, stimulant and cannabis abusers. Anhedonia and craving,
along with typical withdrawal symptoms, may arise independently in the
phase of abstinence from rewarding psychoactive substances, but their
intensity, temporal pattern and treatment responsivity appear not to overlap. Particularly in the so-called protracted withdrawal, the syndrome that
is usually described as depression, but is better interpreted as anhedonia,
cannot be attributed solely to the psychological effects of abstinence.
From a psychobiological perspective a relationship between hypoactivity
of the dopaminergic system and anhedonia in substance use disorders
does exist and is supported by animal models, although in clinical studies
a central receptor dopamine dysfunction was shown to occur as a correlate of affective blunting rather than anhedonia. Imaging studies provided evidence of disrupted sensitivity to natural reinforces in the reward circuits of drug addicted subjects, which could represent a putative mechanism underlying dysphoria and anhedonia experienced during withdrawal.
The same decreased striatal dopaminergic responsiveness was found by
Volkow et al. in detoxified cocaine dependent subjects with craving and
a reduced high experienced in specific pleasant situations. Despite the
employment of various rating scales for its psychometric assessment,
anhedonia is rarely characterized in clinical studies, particularly in substance use disorders. Anhedonia can be measured by a series of specific
scales, such as the Chapmans Physical Anhedonia Scale (PAS) and Social
Anhedonia Scale (SAS), the Fawcett-Clarks Pleasure Scale (FCPS) and the
Snaith-Hamilton Pleasure Scale (SHAPS). The Snaith-Hamilton Pleasure
Scale, built from the responses of a large sample of the general population to the request to list six situations that afford pleasure, was
employed to assess anhedonia in different psychiatric conditions. Other
rating instruments were employed to evaluate anhedonia within broader
psychopathological dimensions, such as those of negative symptoms and
depression. The Scale for the Assessment of Negative Symptoms (SANS)
by Andreasen was used in schizophrenic patients with or without abuse
of cannabis. The Bech-Rafaelsen Melancholia Scale (BRMS) was administered not only to melancholic patients but also to acute schizophrenic
subjects, rating the latent dimension of depressive and negative symptomatology and showing a positive correlation with SANS. Anhedonia was
explored in dependence on substances other than cannabis (alcohol, opiates, cocaine) by using specific scales, such as PAS, SAS and FCPS or
instruments able to detect a broader psychopathological area, such as the
Beck Depression Inventory (BDI) or SANS. A set of instrument employed
56
to assess anhedonia in detoxified substance dependent subjects will be

presented and discussed, together with data concerning the prevalence
of anhedonia in an Italian sample of addicts.
References: Janiri L, Martinotti, G Dario T, Reina, D, Paparello F, Pozzi G,
Addolorato G, Di Giannantonio M, De Risio S: Anhedonia and substancerelated symptoms in detoxified substance dependent subjects: a correlation study. Neuropsychobiology 2005; 52: 37-44. Loas G, Pierson A:
Anhedonia in psychiatry: a review. Ann Med Psychol (Paris) 1989, 147:
705-717. Heinz A, Schmidt LG, Reischies FM: Anhedonia in schizophrenic, depressed, or alcohol dependent patients: neurobiological correlates. Pharmacopsychiatry 1994, 27: 7-10. Diana M, Pistis M, Muntoni A,
Gessa G: Mesolimbic dopaminergic reduction outlasts ethanol withdrawal syndrome: evidence of protracted abstinence. Neuroscience 1996, 71:
411-415. Volkow ND, Wang GJ, Fowler JS, Logan J, Gatley SJ, Hitzemann
R, Chen AD, Dewey SL, Pappas N: Decreased striatal dopaminergic
responsiveness in detoxified cocaine-dependent subjects. Nature 1997,
386 (6627): 830-833.
S-32-04
The role of anhedonia in depression
Hernan Silva
Universidad de Chile, Psiquiatria, Santiago, Chile
Introduction: The pathophysiology of major depressive disorder (MDD)
includes disturbances in several neuroanatomical substrates and neurotransmitter systems. The object of this presentation is to review the brain
mechanisms of MDD behavioral symptoms, chiefly those of anhedonia.
Method: We review the neuroanatomical substrates and the neurotransmitter systems involved in the brain mechanisms of anhedonia in MDD.
Results: Several lines of evidence are consistent with a role of dopaminergic (DA) systems in the pathophysiology of depression, including evidence of altered DA function in depressed patients, pathological mood
symptoms in patients suffering from other diseases that affect DA systems
(principally Parkinsons disease), and the effects on mood of psychopharmacological agents that alter DA neurotransmission. Moreover some antidepressants appear to enhance and may even predominantly act via a
dopaminergic action. Decreased CSF HVA levels have been reported in
depressed patients, as well as in depressed subjects who attempted suicide. The urinary concentrations of DA metabolites are significantly lower
in depressives compared with controls. Another line of evidence is suggested by the mood symptoms that occur in up to 50% patients with
Parkinsons disease. The symptoms of depression often precede the
development of the physical manifestations of the disorder. Results of
neuroendocrine challenge tests are concordant with DA dysfunction in
depression. Functional neuroanatomical studies concludes in altered brain
activation in the ventrolateral prefrontal cortex and the orbitofrontal cortex
and the caudate and putamen in MDD patients. The actions of a number
of different drugs suggest that increasing DA transmission is associated
with improvement in depressive symptoms. The psychostimulants
d-amphetamine and methylphenidate increase DA release, with resultant
increased energy, activation and elevated mood. Although these drugs
cause transient mood elevations in depressed and euthymic individuals,
they are ineffective as antidepressants, at least as monotherapy. Effective
antidepressants as bupropion, amineptine and sertraline are antagonists
of DA transporter. Postsynaptic DA antagonists (haloperidol and chlorpromazine) can produce a syndrome that resembles depression.
Conclusion: Dopamine-related neuroanatomical substrates are involved
in MDD, shedding light on the neurobiology of the anhedonic symptoms
and suggesting these substrates as future therapeutics targets.
References: - Garlow SJ, Nemeroff ChB. The neurochemistry of depressive disorders: clinical studies. In Neurobiology of Mental Illness. Charney
DS, Nestler EJ. (eds). New York, Oxford University Press, 2004. - Trembley
LK, Naranjo CA, Graham SJ, Hermann N, Mayberg HS, Hevenor S, Busto
UE. Functional neuroanatomical substrated of altered reward processing
in major depressive disorder revealed by a dopaminergic probe. Arch Gen
Psychiatry 2005;62:1228-1236
OTHER - Symposia
S-32-05
Anhedonia as a specific target of treatment
Giovanni Martinotti
Univ. Cattolica d. Sacro Cuore, Inst. Psychiatry & Psychology, Rome, Italy
Introduction: The treatment of anhedonia is a complex and poorly discussed issue. The dimension of anhedonia is usually associated with the
broader concept of depression and therefore psychopharmacological
treatments such as SSRI, SNRI are usually proposed as the golden standard. However, anhedonia may be separately considered from both a psychobiological and theoretical point of view. Theories concerning the role
of the dopaminergic mesolimbic system in the origin of pleasure are well
known, therefore it has been often hypothesized that anhedonia is associated with a dysfunction of the mesolimbic dopaminergic reward system.
Some authors have hypothesized that anhedonic subjects might need
intense stimulation in order to compensate for their low emotional reactivity, mediated by a low dopamine tone. Conversely, studies in humans
and non-human animal models indicate that dysfunction of central
dopaminergic neurotransmission interferes with the process of motivation
rather than with the ability to experience pleasure; the latter may be more
mediated by the opioidergic and serotonergic neurotransmission. In other
words, dopamine systems are necessary for wanting incentives, but not
for liking them or for learning new likes and dislikes However, as to
drug addiction, a relationship between hypoactivity of the dopaminergic
system and anhedonia in substance use disorders does exist and is supported by animal models. Imaging studies provide evidence of disrupted
sensitivity to natural reinforcers in the reward circuits of drug addicted
subjects. The role of dopaminergic agents such as pramipexole, dopaminergic partial agonists such as aripiprazole, and tiapride will be discussed.
Besides, promising results concerning the employement of Acetyl-L-carnitine in the treatment of detoxified alcohol dependent subjects with anhedonia will be presented. Acetyl-L-carnitine is an endogenous substance
which plays a fundamental role in the functionality of cell membranes and
in the energetic metabolism; at the CNS level it has shown important
pharmacological activities such as stimulation of the receptor binding,
increase in the NGF levels and improvement of neuronal function, acting
as an acetylcholine precursor.
References: Schmidt K, Nolte-Zenker B, Patzer J, Bauer M, Schmidt LG,
Heinz A: Psychopathological correlates of reduced dopamine receptor
sensitivity in depression, schizophrenia, and opiate and alcohol dependence. Pharmacopsychiatry 2001, 34: 66-72. Willner P: Validity, reliability
and utility of the chronic mild stress model of depression: a 10-year
review and evaluation. Psychopharmacology 1997, 134: 319-329.
Berridge KC, Robinson TE. What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience? Brain Res Brain Res Rev.
1998 Dec;28(3):309-69 Janiri L, Martinotti, G Dario T, Reina, D, Paparello
F, Pozzi G, Addolorato G, Di Giannantonio M, De Risio S: Anhedonia and
substance-related symptoms in detoxified substance dependent subjects:
a correlation study. Neuropsychobiology 2005; 52: 37-44.
S-40
Symposium in memoriam Helmut Beckmann
T12 Other
S-40-01
The contribution of Helmut Beckmann to European
Biological Psychiatry
Siegfried Kasper
focused on psycho-social characteristics. Helmut Beckmann built up a

working group in this department which embarked on several areas of
biological psychiatry like brain imaging, post mortem brain pathology,
biochemical changes in plasma and liquor cerebrospinalis, psychopharmacology as well as psychoneuroimmunology. Helmut Beckmann managed
to bring in international thought leaders on the theme including Dennis
Murphy from NIMH as well as Hans Hippius from Germany. Soon his
interest was focused also on psychopathological characteristics as outlined by Karl Leonhard, an area which he thereafter developed in specific
working groups on national as well as international levels. The way
Helmut Beckmann taught to understand and develop thoughts trained a
large number of young colleagues and made them ready for further steps
in their academic careers: quite a few of them hold now prestigous positions in European psychiatric university institutions. The community dedicated to a biological understanding of mental disorders owe Helmut
Beckmann a lot and is thankful for his contributions.
S-40-02
Working and learning with Helmut Beckmann: Results of a
20 year collaboration
Wagner Gattaz
Sao Paulo, Brazil
This is a presentation of a very personal experience during two decades
of close contact and friendship with Helmut Beckmann, in memorian of
this who was one of the most influential German psychiatrists in the
second half of the 20th century.
S-40-03
The contribution of Helmut Beckmann to the WKL school
of Psychiatry
Alberto Monchablon
University of Buenos Aires, Faculty of Medicine, Argentina
Fifteen years ago I had the honour to meet Prof. Helmut Beckmann in
Buenos Aires. He was invited by Prof. Jorge Ciprian by the time the latter,
assumed as President of the World Federation of Societies of Biological
Psychiatry. With Prof. Beckmann we had an immediate affinity and I invited
him to the Neuropsychiatric Hospital for Women Braulio A. Moyano.
During his visit I introduced him to Prof. Dr. Juan Carlos Goldar, whom
introduced us, at the same time, into the Wernicke-Kleist-Leonhards
thought. It was a privilege for me to visit the hospital, including the
Jackobs Museum, along with these personalities and showing Prof.
Beckmann the rich tradition of the German Psychiatry we had in Buenos
Aires. In the preceding Congresses of the Argentinean Association of
Psychiatrists, we held seven Symposiums of the International WKL Society,
where not only Prof. Beckmann attended but also Professors Ernst
Franzek, Gerald Stber, Klaus-Jgen Neumrker among others. Along the
years, I had the fortune to visit the city of Wrzburg, where
Prof. Beckmann used to work and to participate in several International
Congresses of the WKL held at Budapest, Asuncion del Paraguay,
Gttingen etc. The knowledge I received from Prof. Beckmann was
extraordinary. He distinguished me at Berlin with the Vice-presidency of
the International Wernicke-Kleist-Leonhard Society. During his last stay in
Buenos Aires he gave to me, as a testimony of our friendship and the
respect and recognition we had to each others work, all the clinical cases
he filmed in the Neuropsychiatric Clinic of Wrzburg. Independently of
the political facts that generate changes, the absence of Prof. Beckmann
saddened us all very much as he was a great pillar of world-wide psychiatry and a noble friend.
Introduction: Helmut Beckmann has learned and studied the basis of

understanding mental disorders at the psychiatric department of the
University of Munich and later on at the National Institute of Mental
Health(NIMH)/USA. When he returned from his research at the NIMH
which was dedicated to biochemical changes in depression, he soon was
appointed as Full Professor of Psychiatry at the Central Institute of Mental
Health in Mannheim/Germany,a part of the University of Heidelberg. In
this department the understanding of psychiatric disorders was primarily
57
OTHER - Symposia
S-45
Newer frontiers of biological psychiatry in the
Indian subcontinent
T12 Other
S-45-01
Neuroimaging in alcohol addicts
Vivek Benegal
India
Introduction: Alcohol dependence is a common, etiologically complex
disorder with genetic underpinnings. The disorder aggregates in families
and the morbid risk to relatives of alcoholics is significantly higher than
the risk to individuals in the general population. Subjects at High Risk for
Alcoholism (HR) have been found to differ from low risk individuals (LR),
on a range of neurobiological markers.
Results: We present new data, which demonstrate differences in brain
morphology between alcohol-nave High Risk subjects (child, adolescent
and young adult offspring of early onset male alcoholics with a high family loading for alcoholism) and Low Risk subjects (offspring of nonalcohol dependent fathers without family history for alcohol dependence).
These morphological differences appear to correlate with differences in
attentional processing (P300 wave of the ERP and other indices of central
nervous system hyperexcitability) and manifest externalizing behaviors
which are also known to differentiate these two groups.
Conclusion: These endophenotypic differences may predispose the HR
children to early experimentation with alcohol as well as lowered subjective response and increased reinforcement to ethanol, leading to early
and frequent use of ethanol. We hypothesize that this may represent an
integral pathway for the known susceptibility of these individuals to early
alcohol related problems.
References: Benegal V, Venkatsubramanian GV, Antony G, Jaykumar P.N
(2007) Differences in brain morphology between subjects at high and low
risk for alcoholism. Addiction Biology Chagas Silva M, Mukundan CR,
Benegal V (2007) Marfatia Award Paper: P300 Deficits in Children at High
Risk for developing Alcohol Dependence. Indian Journal of Psychiatry [In
press] Muralidharan K, Venkatasubramanian G, Pal PK, Benegal V.
Transcallosal Conduction Abnormalities in Alcohol-naive Male Offspring
of Alcoholics. [Under review] Venkatasubramanian G, Anthony G, Reddy
US, Reddy VV, Jayakumar PN, Benegal V. (2007)Corpus Callosum
Abnormalities Associated with Greater Externalizing Behaviors in Subjects
at High Risk for Alcohol Dependence. Psychiatry Research: Neuroimaging
S-45-02
Psychiatric genetic research in India
Rajesh Nagpal
Manobal Klinik, New Delhi, India
Introduction: The concept of family tree (vansha)is inherent in Indian culture. The genealogy of specific families (gotra) is preserved with the
priests in holy towns in India. With the human genome project, there is
growing interest in genetic research in India.
Method: The studies conducted are disparate, ill coordinated & lack a
coherent core. A strategic approach to psychiatric genetic research is
imperative in our national interests. Ethical safe guards, laws regarding
transfer of biological material, intellectual property, genetic counseling
merit review at the highest levels. Epidemiological information, ongoing
gene mapping efforts & exciting breakthroughs like RGS4 are reviewed.
Results: The ongoing research is compared to the Western initiatives &
putative time line of progress mapped.
Conclusion: Genetic epidemiological studies of several psychiatric disorders are in progress in India, but these studies do not appear to be coordinated. It is vital in the national interest, to develop a coherent core of
clinical genetic research programmes.
References: 1. Aravindakshan M, Sitasawad S, Debsikdar V, Ghate M,
Evans D, Horrobin DF, Bennett C, Ranjekar PK, Mahadik SP. Essential
polyunsaturated fatty acid and lipid peroxide levels in never-medicated
and medicated schizophrenia patients. Biological Psychiary
2003;53(1):56-64. 2. Blouin JL, Dombroski BA, Nath SK, Lasseter VK,
58
Wolyniec PS, Nestadt G, Thornquist M, Ullrich G, McGrath J, Kasch L,

Lamacz M, Thomas MG, GehrigC, Radhakrishna U, Snyder SE, Balk KG,
Neufeld D, Swartz KL, DeMarchi N, Papadimitriou GN, Kikeos DG,
Stefanis CN, Chakravati A, Childs B, Pulver AE. Schizophrenia susceptibility loci on chromosomes 13q32 and 8p21. Nature Genetics
1998;20(1):70-73. 3. Chowdari KV, Xu K, Zhang F, Ma C, Li T, Yong Xie
B, Wood J, Trucco M, Tsoi W, Saha N R, Rudert WA, Nimgaonkar VL,
Immune related geneti polymorphisms and schizophrenia among the
Chinese, Human Immunology 2001b;62(7)714-724. 4. Ganguli M.
Chandra V, Kamoboh MI, Johnston JM, Dodge HH, Thelma BK, Juyal RC,
Panday R, Belle SH, DeKosky ST. Apolipoprotein E polymorphism and
Alzheimers disease: The Indo-US cross-national dementia study. Archives
of Neurology 2000;57(6):824-830. 5. Reddy PS, Janardhan Reddy YC,
Srinath S, Khanna S, Sheshadri SP, Girimaji SC. A family study of Juvenile
obsessive compulsive disorder. Canadian journal of Psychiatry
2001;46:346-351. 6. Saleem Q, Dash D, Gandhi C, Kishore A, Benegal
V, Sherrin T, Mukherjee O, Jain S, Branmachari SK, Association of CAG
repeat loci on chromosome 22 with schizophrenia and bipolar disorder,
Molecular Psychiatry 2001b; 6(6):694-700. 7. Verma IC. Burden of genetic disorders in India. Indian Journal of Pediatrics 2000;67(12):893-898
S-45-03
John Alex
India
S-45-04
Role of SPECT in depression
G. Prasand Rao
India
Introduction: The role of Brain Spect in Depression was studied initially
and significant changes in the drug naive patients of major depressive disorder (DSM IV R ) were studied. As compared to age, sex, matered controls, significant difference emerged.
Method: Brain Single Photon Emission Tomograph is a useful tool to
measure the brain blood perfusion. As it is relatively cheap as investigative tool, in developing countries like India it has been used as useful tool
of investigation.
Results: The useful role of Electro convulsive treatment in major depressive disorder is well established. The exact mechanisms of action of ECT
is not yet established. The regional cerebral blood flow ( r CBF) changes
in varieties of psychiatric disorders are well recognised investigation in
recent times to understand the biological basis of psychiatric disorders.
Brain Single Positron Emission Tomograph ( Brain SPECT) is used as a tool
in the measurement of r CBF. In this prospective study patients (N 10) who
are Drug Naive and suffering from major depressive disorder (MDD) diagnosed according to DSM IV criteria were taken as study sample. The r CBF
in the sample were studied using Brain SPECT during Drug Naive period,
during the first ECT and after six weeks of completion of course of ECT.
Significant changes of hypo perfusion was observed in Orbito frontal,
ant. Parietal, post.Parietal, and temporal bilaterally. This hypo perfusion
changes returned to normalcy six weeks after the course of ECT. No
statistically significant differences of rCBF of post ECT values and normal
controls were observed indicating the reduction in hypo perfusion is possibly a state dependent phenomena.
Conclusion: An early study of PET scan in few patients of major depressive disorder is being attempted. Results would be presented. Limitations
with Brain spect & PET studies would be discussed.
References: *Abdel-Dayem HM, El-Hilu S. SchweilA et al. Cerebral perfusion changes in schizophrenic patients using TC.99M hexa methyl
propylene amine oxime (HMPAO) Clinical Nuclear Med 1990 15: 468472 . *American Psychiatric Association. The practice of E.C.T. recommendation for treatment, training and privileging convulsive therapy
1990, 6, 85-120 *American Psychiatric Association; Diagnosis and statistical Manual for Mental Disorders Edition 4. Washington DC. APA 1994.
*Amsterdam J.D., Mozley P.D.; Temporal lobe assmymmetry with iofetamine (IMP) APECT Imaging in patients with major depression; J. Affect
Disorder 1992, 24, 43 - 53.
OTHER - Symposia
S-48
Current biological studies and theories of personality disorders
T12 Other
S-48-01
What neuroimaging can tell us about symptoms found in
patients with personality disorders
Kenneth Silk
University of Michigan Health, Psychiatry, Ann Arbor, USA
T. Love, S. Guduri, J. Zubieta
Brain circuitry and neurochemical systems involved in pain regulation may
be implicated in emotion regulation. There is evidence that the -opioid
system is involved in regulation of affective responses to emotional and
stressful stimuli and is known to be activated to suppress sensory aspects
of negative internal affective states. Emotion dysregulation (lability) has
been proposed as an endophenotype in borderline personality disorder
(BPD). In healthy women, a reduction of -opioid neurotransmission
occurs in anterior cingulate, ventral pallidum, and amygdala in response
to sustained sadness induction. Our hypothesis: subjects (Ss) with BPD
would present with (a) higher baseline -opioid system activity than controls and (b) abnormal activity enhancements (increased activation) in
response to a negative (sustained sadness) state. Method: R-handed
females > 18 years old who meet SCID-II criteria for BPD. Exclusions: no
head trauma, ongoing medical problems, medications for two weeks, axis I
disorder other than mood disorder, history of chronic, prolonged substance misuse. Ss underwent [11C] carfentanil PET scans for two cued
recall conditions: NEUTRAL state and SAD states that were randomized,
counterbalanced, at 5-45 min and 45-100 min post tracer. Ratings:
PANAS sadness q10 min during scan and PANAS Negative and PANAS
Positive Affect ratings before and after each state. N= 8 BPD Ss; 18 controls. Ss were age-matched. Results: (1) Neutral condition: BPD Ss showed
increased -opioid binding potential (BP [a measure of regional deactivation of -opioid neurotransmission]) of the tracer compared to controls in
the L orbitofrontal and R temporal cortex and R and L caudate. Controls
showed decreased BP in the dorsal anterior cingulate. (2) Sad: BPD Ss
showed regional deactivation (increased BP) in L nucleus accumbens, R
ventral basal ganglia, and extended amygdala. (3) Neutral minus sad: BPD
Ss showed regional -opioid activation (decreased BP) in L and R amygdala and hypothalamus while controls showed little change from neutral
to sad state in most of these areas. Conclusions: Emotion regulation (sadness) appears to be mediated by the -opioid system, but BPD Ss respond
differently from controls in terms of (1) activation and deactivation and (2)
in regions reacting.
S-48-02
The biological bases of the integrative treatment of personality disorder
Nestor Koldolbsky
La plata national medicine, school-iaepd, Argentina
Personality disorders are going to be a bridge and an integrative aspect
between biological and psychosocial factors that are behind them. There
is a group of therapeutic techniques that necessarily have to recognize
the existence of temperamental and character basis for etiology, development, clinics and therapeutics of PD. Temperament as a resume of biological aspects and character, of the psychosocial aspects, could not be considered from a dichotomous view. Psychopharmacology and psychotherapy themselves had an increasing connection with the neuroscience
advances that permit the knowledge of the biological basis of their mechanism. The increasing of evidence mechanism: the neurobehavioral systems underlying higher order personality traits, anxiety and neuroticism,
impulsivity, neurobiology of affective traits, biological/genetic vulnerabilities, neurobiology of trauma, etc. will permit to integrate biological and
psychological aspects to get much more sophisticated and integrated
treatment systems.
S-48-03
NMDA neurotransmission and the neurobiology of borderline personality disorder
Bernadette Grosjean
Harbor u.c.l.a., Psychiatry, Torrance, USA
Introduction: Studies of the neurobehavioral components of borderline
personality disorder (BPD) have shown that symptoms and behaviors of
BPD are, in part, associated with disruptions in basic neurocognitive processes, in particular in the executive neurocognition and memory systems.
Recently, a growing body of data indicates that the glutamatergic system,
in particular the N-methyl-D-aspartate (NMDA) subtype receptor, plays a
major role in neuronal plasticity, cognition and memory, and may underlie the pathophysiology of multiple psychiatric disorders.
Methods: This presentation reviews and articulates recent neurobiological data in dysfunctions of NMDA receptor-mediated neurotransmission
in the etiopathology and symptomatology of BPD.
Results: Multiple cognitive dysfunctions and symptom presentations like
dissociation, psychosis and impaired nociception in BPD may result from
the dysregulation of the NMDA neurotransmission. This impairment may
be the result of the combination of biological vulnerability and environmental influences mediated by the NMDA neurotransmission.
Conclusion: The role of NMDA neurotransmission as a critical modulator
for neuroplasticity is well recognized. Dysfunctions of the NMDA neurotransmission by environmental factors, in particular by stress, trauma, or
neglect, impacts cognition, emotion, affect, motivation, appraisal and
evaluation of environmental stimuli. These may be particularly evident in
the psychopathology of BPD and could suggest a new therapeutic
approach for BPD.
References: Grosjean.B.,Tsai.G."NMDA Neurotransmission as a Critical
Mediator of Borderline Personality Disorder." Journal of Psychiatry and
Neuroscience (under review 2006.)
S-48-04
How trauma reinforces the symptoms of borderline personality disorder
Ernesto Figueroa
Saint Joseph Mercy Hospital, Psychiatry, Ann Arbor, USA
Introduction: The study of Borderline Personality Disorder (BPD) has
evolved from primarily a psychoanalytic approach towards an integration
of psychological and biological factors. This integration into conceptualizing personality as well as personality disorders in terms of having roots
in both biological as well as life or environmental factors has provided an
impetus to investigate the biological underpinnings of dimensions or
components of personality. Those dimensions, including dimensions
most impacted in BPD, include impulse, affective regulation and cognitive perceptual dimensions. Neurobiology and brain imaging techniques
provide us with new tools to examine the brain, and recent efforts have
tried to tie more closely the dimensions of personality to these neurobiology and structural findings. This presentation is an effort to review the
current research of basic trauma and how it may affect the dimensions
mentioned above.
Method: The literature on the neurobiology and imaging of BPD was
reviewed with the purpose of conceptualizing BPD in terms of the core
dimensions that are presented as symptoms or criteria of BPD. These
include impulse dyscontrol/hostility, affective instability and cognitive perceptual distortions.
Results: The strongest evidence is for a relationship between impulsivity
and serotonin dysregulation. There is some evidence that affective instability might be mediated at least in part by GABA and glutamate and that
cholinergic and noradrenergic circuitry might be involved in affect regulation. There is also evidence suggesting that dopamine pathways might
mediate cognitive perceptual distortions. When these disturbances are
combined in a unique way, we come to the clinical presentation of the
phenomenon called BPD. In addition, a growing body of evidence indicates that early trauma results in HPA axis hypersensitivity, which in turn
might be related to dysfunction of the hippocampus.
Conclusion: Further understanding of the core dimensions of psychopathology of BPD may provide us with more order and less chaos in
our thinking about and application of treatments to a disorder where
chaos and inconsistency are often part of its clinical presentation.
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ADDICTIVE DISORDERS - Free Communications
Free Communications
FC-13
Addictive Disorders
FC-13-01
Internet addiction: The Bolivian college students case
Guillermo Rivera
Santa Cruz, Bolivia
Introduction: This study explores Internet addiction among some of the
Bolivas college students. Also covered are a discussion of the Internet as
a form of addiction, and related literature on this issue.
Method: Two hundred and ten valid surveys were collected from 12 universities and colleges around Taiwan.
Results: The results indicated that Internet addiction does exist among
some of Bolivia`s college students. In particular, 14 students were identified as Internet addicts. It was found that Internet addicts spent almost
triple the number of hours connected to the Internet as compare to nonaddicts, and spent significantly more time on BBSs, the WWW, e-mail and
games than non-addicts. The addict group found the Internet entertaining, interesting, interactive, and satisfactory. The addict group rated
Internet impacts on their studies and daily life routines significantly more
negatively than the non-addict group.
Conclusion: The study also found that the most powerful predictor of
Internet addiction is the communication pleasure score, followed by BBS
use hours, sex, satisfaction score, and e-mail-use hours.
References: - Kyunghee Kima, Eunjung Ryu & cols. Internet addiction in
Korean adolescents and its relation to depression and suicidal ideation: A
questionnaire survey. International Journal of Nursing Studies. Volume 43,
Issue 2 , February 2006, Pages 185-192 - Ng Brain, Wiemer-Hastings
Peter. Addiction to the Internet and Online Gaming. CyberPsychology &
Behavior. Apr 2005, Vol. 8, No. 2: 110-113
FC-13-02
Prospective memory impairments associated with ecstasy
use: A comparative study of users and non-users
Thomas Heffernan
Northumbria University, Division of Psychology, Newcastle-Upon-Tyne,
United Kingdom
Introduction: Persistent use of MDMA or ecstasy' has been associated
with a range of psychological problems, including memory deficits.
Despite this, little research has investigated the possibility of deficits in
prospective memory (PM) ability (memory for future intentions) in ecstasy
users. The present study extended this research by comparing ecstasy
users and non-users on both self-report and objective measures of PM
whilst controlling for age, use of strategies to assist remembering, use of
other substances and mood states.
Methods: A non-experimental design was used. An opportunity sample
of 53 participants comprising 23 ecstasy users and 30 non-users participated in the study. Each participant completed a video-based prospective
memory task and the self-report Prospective Memory Questionnaire
(PMQ) which measured PM lapses. A substance-use questionnaire measuring weekly use of cannabis and other substances, and a Profile of Mood
States questionnaire (POMS) which measured a range of mood states
were also used. The order of presentation of the measures was held constant across participants.
Results: A series of ANCOVAS revealed that ecstasy users did consume
more alcohol, smoked more cigarettes, and used more cannabis, than the
non-users, with no differences between the groups on age, strategy-use,
or mood scores. After controlling for alcohol, cigarettes and cannabis, a
MANCOVA revealed that ecstasy users reported more long-term PM lapses and recalled less items on the video-based PM task, than non-users.
Conclusion: This research supports the notion that everyday PM deficits
are associated with recreational use of ecstasy.
60
FC-13-03
Opioid maintenance therapy in pregnant women consequences?
Nina Ebner
Klosterneuburg, Austria
Klaudia Rohrmeister, Bernadette Winklbaur, Andjela Baewert, Reinhold
Jagsch, Alexandra Peternell, Kenneth Thau, Gabriele Fischer
Introduction: Treating opioid-dependent pregnant women poses a
major challenge to treatment providers. The aim of our study was a comparison of birth parameters and assessment of incidence and timing of
neonatal abstinence syndrome (NAS) in 53 neonates of opioid-dependent
women, who were maintained on three different synthetic opioids during
pregnancy (22 women received methadone, 17 women oral slow-release
morphine and 14 women were maintained on buprenorphine).
Furthermore, two different pharmacological approaches in the treatment
of the NAS were examined (phenobarbiturate versus morphine
hydrochloride).
Method: Fifty-three neonates born to opioid maintained mothers, who
showed no concomitant consumption, were scored four-hourly using a
modified version of the Finnegan Score to assess the NAS. 15 of the 32
infants, who required pharmacological treatment, received phenobarbital, 17 received morphine hydrochloride. Maternal treatment and outcome in neonates (APGAR-Scores, weight, length, head circumference)
were compared.
Results: We could not find significant differences in regard to APGAR
Scores, weight, length or head circumference in the three groups. Sixty
percent (n=32) of infants required treatment for NAS. Seven neonates of
this group were born to methadone-treated mothers, three to oral slowrelease morphine and eleven to buprenorphine-maintained mothers. A
significant proportion of infants of buprenorphine-maintained mothers
did not require medical treatment of NAS (p=0.002). The mean duration
from birth to initiation of treatment was 33 hours for slow-release morphine, 34 hours for buprenorphine and 57 hours for methadone.
However, the difference was not statistically significant (p=0.17). Infants,
to whom oral morphine hydrochloride was administered had a significantly shorter duration of NAS-treatment (9.9 days) than neonates treated with phenobarbiturates (17.7 days).
Conclusion: Efficient pharmacological maintenance treatment of opioiddependent women during pregnancy and of their neonates after delivery
(NAS-treatment) result in positive outcomes.
References: Jones, H.E., Johnson, R.E., Jasinski, D.R., OGrady, K.E.,
Chisholm, C.A., Choo, R.E., Crocetti, M., Dudas, R. Harrow, C., Huestis,
M.A., Jansson, L.M., Lantz, M., Lester, B.M., Milio, L., 2005.
Buprenorphine versus methadone in the treatment of pregnant opioiddependent patients: effects of the neonatal abstinence syndrome. Drug
and Alcohol Depend. 79, 110.
FC-13-04
Mu opioid receptor regulation in human cocaine users
Karley Little
University of Michigan, Dept. of Psychiatry, Ann Arbor, USA
Courtney Roland, Bader Cassin
Introduction: Brain dopamine neuronal function is altered in human
cocaine users, perhaps contributing to withdrawal effects and persistent
dysphoria. Animal data suggests that changes in post dopamine circuitry
may cause long term craving. The present experiment tested the hypothesis that striatal and ventral pallidal mu opioid receptors would demonstrate signs of supersensitive function in human cocaine users.
Method: Mu opioid receptor function was autoradiographically assessed
using [3H ]DAMGO binding, a mu receptor agonist, and DAMGO-invoked
[3H]GTP binding. Sections from anterior striatum, including accumbens,
and ventral pallidum, were examined from 21 subjects diagnosed as
cocaine dependent prior to death, and 21 age-, sex-, post mortem interval-, and race-matched controls. All specimens were dissected 24 hrs or
less after death. Both cocaine-dependent and control subjects died suddenly of cardiovascular cause or trauma.
ADDICTIVE DISORDERS - Free Communications
Results: Both [3H ]DAMGO and DAMGO-invoked [3H]GTP binding were

increased in cocaine dependent subjects. There was a direct correlational relationship between increases in mu receptor measures and dopamine
transporter binding increases.
Conclusion: Both dopaminergic and opioidergic alterations occur in
human cocaine users. Each type of pertubation may contribute to distinct
symptoms that complicate efforts to control cocaine use.
References: Little, K.Y. Zhang, L., Desmond, T., Frey, K.A., DalackG.W.,
Cassin, B.J. Striatal dopaminergic alterations in human cocaine users. Am
J Psychiatry, 156:238-245, 1999 Little, K.Y., Krolewski, D.M., Zhang,
L.Cassin, B.J. Loss of striatal vesicular monoamine transporter (VMAT2) in
human cocaine users. Am J Psychiatry 160:47-55, 2003
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AFFECTIVE DISORDERS (BIPOLAR) - Free Communications
FC-02
Affective Disorders (Bipolar)
FC-02-01
Bipolar depression in children and adolescents, an
overview
Margarita Garcia-Amador
Hospital Clinic, Psychiatry, Barcelona, Spain
Marc Valenti, Eduard Vieta, Josefina Castro
Introduction: Bipolar depression (BDp)is a difficult diagnosis and affects
importantly the functionality of a population in an outstanding period of
learning, acquiring social skills and neurocognitive development.
Method: Studies were identified through electronic searches of MEDLINE, EMBASE and Biological Abstracts using index terms for bipolar disorder, bipolar depression;combined with children and adolescents,suicide;and combined with terms for risk,longitudinal studies.
Results: Population studies reveal a prevalence of bipolar disorder in1%
of adolescents. Postpuberal girls present more frecuently bipolar depression. Clinical presentation is heterogenous. Moreover, bipolar depression
is the first clinical presentation in a percentage as high as 40% percent of
this population (1). Familiar humor disorder history, high irritability, lability, high recurrence and substance abuse are highly represented in
depressed children that would become bipolar. The COBY study (2)
showed that the majority of recurrences of bipolar disorder are depression
(57.5%) in the different bipolar subtypes (I, II, NOS) for children.
Moreover, patients were symptomatic during 60% of the prospective
study and presented generally depressive symptoms. Suicidal ideation
raise in depressive phases (3). Functionability is highly compromised specially in depressed phase. Comorbidity is important due to the increase of
suicidability and its bad prognosis: Anxiety and substance abuse, the most
important. As far as we know, treatment for bipolar depression in children and adolescents does not differ from the treatment in adults:
Indeed, lithium is the most used treatment. New indications are recently
increasing in importance, specially for the lamotrigine, but also for the
second generation antipsychotics. Antidepressives are to be used but
always in association with mood stabilizers and the ECT is to be considered. Nonetheless extensive studies in this special population are to be
done.
Conclusion: BDp is a complex diagnose that can be the first presentation
of bipolar disorder. Acurate diagnose and treatment are of extreme
importance for the disease evolution and the future functionality.
Research on bipolar offspring is of high interest for prospective control.
References: 1.Geller B, et al. Bipolar disorder at prospective follow-up of
adults who had prepubertal major depressive disorder. Am J Psychiatry
2001; 158: 125-127. 2.Birmaher B, et al. Clinical course of children and
adolescents with bipolar spectrum disorders. Arch Gen Psychiatry. 2006
Feb;63(2):175-83. 3.Goldstein TR, et al. History of suicide attempts in
pediatric bipolar disorder: Factors associated with increased risk. Bipolar
disorders. 2005; 7: 525-535.
FC-02-02
Effects of psychotropics on glycosylated hemoglobin
(hba1c) in a cohort of bipolar patients
Ruby Castilla-Puentes
University of North Carolina, Department of Psychiatry, Philadelphia, PA,
USA
Introduction: Research suggests that certain psychotropics may induce
glucose regulatory dysfunction. Hyperglycemia increases levels of HbA1c.
This study investigated the relationship between psychotropic use and
concentration of HbA1c in presumptively nondiabetic bipolar patients.
Method: Analysis was conducted on 76,671 bipolar (BPD) patients from
the Integrated Healthcare Information Services (IHCIS). Included were
381 patients with at least two measurements of HbA1c from January 1,
1997 through June 30, 2002. Individuals with only one HbA1c measure,
diagnosed with Type 1 or Type 2 Diabetes in ICD-9, and/or using any
antidiabetic medication were excluded from the cohort. HbA1c levels
62
from first to final HbA1c measurements were compared. The type of psychotropic medication used by the patients was also examined.
Results: One hundred ninety seven (51.9% ) of BPD patients had an
abnormal initial HbA1c test result (defined as: HbA1c >7) .Of 231 patients
who were taking psychotropic medication, 30 patients were taking
antipsychotics, 24 mood stabilizers (anticonvulsants), 10 lithium, 51 antidepressants, 116 were taking a combination of medications and 150
patients were not taking psychotropic medications. HbA1c levels declined
significantly in patients taking psychotropic medication(s) (mean, SD
7.4+/-2.0% vs. 6.9 +/-1.8%, p=0.001) and in patients not taking psychotropic medication(s) (7.5+/-2.1% vs. 6.9 +/-1.8%, p=0.001). The only
exception to this finding was among patients taking antipsychotics,
where there was a slight increase (not statistically significant) during this
period (7.0+/-1.8% vs. 7.2 +/-3.7%, p<0.791).
Conclusion: These results support findings suggesting an increased risk
of type 2 diabetes in BPD patients. Mood stabilizers (anticonvulsants),
antidepressants, and lithium monotherapy and combination were associated with a decrease in HbA1c levels. Although not statistically significant, antipsychotic medications were associated with an increase in
HbA1c in this population.
References: 1. Brambilla P, Barale F, Soares JC. Atypical antipsychotics
and mood stabilization in bipolar disorder. Psychopharmacol
2003;166(4):315-332.
FC-02-03
Cognitive and neural mechanisms of emotion dysregulation in affective and non-affective psychoses
Melissa Green
University of NSW, Psychiatry, Black Dog Inst. Building, Randwick,
Australia
Gin Malhi
Introduction: Emotion regulation involves the cognitive manipulation of
subjective and physiological experiences of emotion. Recent neuroimaging studies implicate distinct patterns of prefrontal cortical inhibition of
sub-cortical regions in association with particular cognitive regulatory
strategies, alongside modulation of autonomic responses associated with
various forms of negative affect (Green & Malhi, 2006). The use of maladaptive cognitive regulatory mechanisms is associated with altered neural activity in healthy individuals, and increased negative affect in healthy
and clinical populations. Cognitive and neurophysiological models of
affective and non-affective psychoses may emerge from further investigation of emotion dysregulation in these disorders using integrative
methodology within a cognitive neuroscience framework.
Method: The role of emotion dysregulation in the development and
maintenance of affective and psychotic symptoms is considered from a
cognitive neuroscience perspective. Neuropsychological and social-cognitive processes involved in emotion regulation are discussed in the context
of neural mechanisms of cognitive control and emotion processing in
healthy individuals. The symptoms of affective (bipolar, schizoaffective)
and non-affective (schizophrenia) psychotic disorders are considered as
manifestations of emotion dysregulation according to known neuropsychological and social processing deficits, and clinical neuropathology.
Results: Emotion regulation relies on synergy within bidirectional frontostriatal-thalamic and brainstem networks involved in emotion perception,
affect generation, and control of the autonomic nervous system.
Convergent evidence from cognitive neuropsychological and neurobiological investigations in affective and non-affective psychoses implicates
differential dysfunction in these neural systems supporting the cognitive
regulation of emotion.
Conclusion: The cognitive control of emotion may be disrupted by
abnormalities in cognitive and/or neural processes subserving social perception, affect generation, or regulation. Consideration of the neuropsychological and social-cognitive profiles of affective and non-affective psychoses alongside regional neuropathology suggests the existence of distinct patterns of emotion dysregulation in these conditions.
References: Green, M.J. & Malhi G.S. (2006). Neural mechanisms of the
cognitive control of emotion, Acta Neuropsychiatrica, 18, 144-153.
AFFECTIVE DISORDERS (BIPOLAR) - Free Communications
FC-02-04
Serum lipid levels in female patients with affective disorders
Dorotea Muck-Seler
R.Boskovic Institute, Division of Molecular Medicine, Zagreb, Croatia
Marina Sagud, Alma Mihaljevic-Peles, Nela Pivac, Miro Jakovljevic,
Ljubomir Hotujac
Introduction: Lipids are the important constituent of the neuronal cell
membrane. The role of the serum lipids (total cholesterol, high-density
lipoprotein cholesterol /HDL-C/, low-density lipoprotein cholesterol /LDLC/, triglycerides /TG/) in the pathophysiology of the mood disorders is not
clear. The aim of this study was to determine serum lipids profiles in
patients with major depression, bipolar depression and healthy control.
Method: The study included medication free female subjects: 41 patients
with bipolar disoder (22 in manic and 19 in depressive phase), 34 patients
with major depression and 37 healthy controls. Patients were classified
according to DSM-IV criteria. Serum lipids levels were determined using
standard laboratory tests.
Results: Patients with major depression and bipolar disorder in both
phases had lower HDL-C levels than healthy controls. Increased TG levels
were found in patients with bipolar disorder as compared to healthy subjects. The changes in lipids profiles persisted when data were adjusted for
age and smoking. There were no changes in the other lipids levels. A significant differences were found in the ratios of the cholesterol/HDL-C and
LDL-C/HDL-C (atherogenic index) among groups. A negative correlation
between cholesterol levels and YMRS total score was observed in manic
patients.
Conclusion: The results suggest that low HDL-C levels and the ratios of
the cholesterol/HDL-C and LDL-C/HDL-C could be the hallmarks of the
affective disorders. Since low HDL-C levels could be a risk factor for the
development of coronary heart disease, further investigation of the lipids
metabolism in affective disorders is warranted
63
AFFECTIVE DISORDERS (UNIPOLAR) - Free Communications
FC-06
Affective Disorders (Unipolar)
FC-06-01
Neuroplasticity and treatment-resistant depression
Wolfgang Kaschka
University of Ulm, Psychiatry I, Ravensburg, Germany
Martin Jandl
Introduction: In recent years, developments in the field of treatmentresistant depression not only brought about improved definition and classification, but also led to an increase of our knowledge on the etiology
and determinants of treatment resistance.
Results: A number of novel treatment strategies, such as different brain
stimulation methods, have been suggested which will have to be critically evaluated and integrated into an evidence-based therapeutic concept.
Conclusion: The present contribution provides an overview of these
developments with special regard to neuroplasticity and reveals promising
research perspectives which can be expected to bring about an extension
of our knowledge on the etiology and pathogenesis of depressive disorders and may thereby lead to the development of innovative therapeutic
strategies for treatment-resistant depression.
References: Kaschka, W.P., Jandl, M.: Treatment-resistant depression - an
update. Nervenheilkunde 2005; 24: 317-321
FC-06-02
Somatic symptoms in depression-body and the mind
David Wong
University of Hong Kong, Peoples Republic of China: Hong Kong SA
Siu Wa Tang
Introduction: Patients when alerted by physical symptoms assume that
they are physically wrong when they attend their family doctors. Both are
often puzzled when causes cannot be identified. In fact, somatic symptoms are highly prevalent in depressed patients in primary care. Analysis
of the symptom prevalence in an European survey of 1884 patients under
treatment for depression(the Depression Research in European Society II
Study - DEPRESS II ) showed 2 of the 3 commonest symptoms reported in
current depressive episode were somatic. An observational study in by
Tamayo,J.M.et al showed that 100% patients with MDE reported some
forms of somatic symptoms on initial visits. The somatic symptoms of
insomnia, fatigue, appetite and weight changes were included in the
DSM IV and represent one third of the total nine items. The Hamilton rating scale for Depression listed a total of twenty one items and eight of
them are somatic symptoms. Not included in these scales are many other
somatic symptoms observed frequently in family practices most of which
cannot be explained medically. One important example is severe pain. Of
all symptoms, pain, especially its diffuseness and the extent to which daily
activities are interfered is a strong predictor of depression. Severe pain as
a somatic symptom at baseline has also been shown to be a strong predictor of poor response to treatment. A series of cases with initial complains of pain and other somatic symptoms with a final diagnosis of major
depression and their response to antidepressant treatment at a private
practice clinic will be presented.
Method: The records of patients suffering from depression of a private
clinic in general practice were reviewed. A retrospective analysis of the
presenting symptoms were performed with respect to the diagnosis,
course of illness and treatment of depression.
Results: Most depressed patients present to the general practitioner with
somatic symptoms. Presence of such symptoms may have an impact on
diagnosis (in terms of predictive value,confusion and missed diagnosis),
the course of illness (in terms of response, remission and recurrence,
severity and length of illness) and treatment. Antidepressants may stop
somatic symptoms.
Conclusion: The mind is closer to the body than previously thought.
Whilst the mechanism of the linkage awaits clarification observational evidence supports that depression is a disease not only of the mind but the
body as well.
64
FC-06-03
Immunology: Schizoprenia and depression
Enrique Galli
Clinica Ricardo Palma, Psiquiatria, Lima, Peru
Introduction: The first Immunological studies in schizophrenia (Heath,
1954 - 1969), are pioneering works that suggest the inflammatory nature
of this disease. Then the Russian authors like (Korenevskaya, 1967),
(Pospisilova and Janik, 1968) found increase of the immunoglobulin in
schizophrenia. The subscribed one in 1971 - 1972 studied immunoglobulin in schizophrenics and depressed patients and found them elevated,
in addition we found non specific antibrain antibodies. In the last 20 years
there has been found a series of alterations in the cytokines, the Th1 and
the Th2, among others. With regard to depression, Fessel (1961, 1962
and 1963), finds increased rheumatoid factor in depressed just like the
subscribed one in 1972 and at the moment there is abundant evidence
on that the immune system can modulate the central neurotransmission
function and the endocrine function in depression. The inflammatory
cytokines are increased in depression. Cytokines IL-4 and IL_10 are lowered in depression. Would depression and the schizophrenia medical
inflammatory disease?
References: 1.Galli E. (1996): Investigacin Inmunolgica en Pacientes
Esquizofrnicos. Anales del I Congreso Peruano de Psiquiatria Biolgica.
Noviembre. Lima Peru. 2.Petitto J. M.(1999): Clinical Neuroinmunology:
Understanding the Development and Pathogenesis of Neuropsychiatry
and Psychosomatic Illnesses. Oxford Neurobiology of Mental Illness.
3.Galli E. (1999): Neuroimmunologic Aspects in Schizophrenia. Anales del
XI Congreso Mundial de Psiquiatria. Hamburgo. 4.Stuebner S. et al.
(1999): Interleukin-6 and the Soluble IL-6 receptor are Decreased in
Cerebrospinal Fluid of Geriatric Patients With Major Depression: No
Alteration of Soluble gp 130. Neurosci. Left. 259:145-8. 5.Leonard B.
(2005): Immunology in Depression and Anxiety: The Role of Cytokines.
Focus on Psychiatry. The Netherlands.
FC-06-04
Past and present major depression predicts in-hospital
mortality in medical inpatients
USA
E.D. e. Aguas
Introduction: To determine whether a history of depression and current
depression predicts mortality independent of severity of medical condition.
Method: Of 2,350 consecutive medical inpatients, 1,457 were interviewed within the first 5 days of admission and 893 were excluded from
the study. A clinical interview that included the Schedule for Affective
Disorders and Schizophrenia was used to determine demographic variables and psychiatric diagnoses. Diagnoses included major depressive disorder and dysthymia diagnosed according to DSM-IV criteria that included all symptoms regardless of etiology and according to criteria modified
for the medical condition (depressive symptoms were eliminated if easily
explained by medical illness, treatments, or hospitalization; anhedonia,
hopelessness or depression were used as the qualifying affective symptoms). A chart review was used to identify past psychiatric history and diseases measures. The Charlson combined age-comorbidity index was used
to measure severity of medical disease.
Results: A diagnosis of major depressive disorder for patients with medical disease predicted mortality. A past history of depression and the
Charlson combined age-comorbidity index predicted in-hospital mortality,
but demographic variables, dysthymia, pain, length of stay and medical
diagnoses did not. In the final multivariate logistic regression model, the
Charlson combined age-comorbidity index, a diagnosis of major depressive disorder, and a history of depression were independent predictors of
in-hospital death.
Conclusion: Diagnosis of major depressive disorder, a past history of
depression and severity of medical illness, independently predicted in-hospital mortality in medical inpatients.
References: 2. Whooley MA, Browner WS (Study of Osteoporotic
Fractures Research Group): Association between depressive symptoms
and mortality in older women. Arch Intern Med 1998; 158:15-24
FC-14
Affective Disorders (Unipolar) II
FC-14-01
Prevalence of major depressive disorder in a populationbased sample of German adults: Preliminary results
Pablo Toro
Psychiatr. Unveristtsklinik, Sektion fr Gerontopsychiatrie, Heidelberg,
Germany
Introduction: Affective disorders are among the most frequent conditions in the elderly, but only a few epidemiological studies are available for
the German population. We therefore established the prevalence and clinical course of affective disorders within the Interdisciplinary Longitudinal
Study on Adult Development and Aging (ILSE).
Methods: Incidence and prevalence of affective disorders were investigated in 500 community-dwelling subjects from the birth cohort 1930/32 of
two German urban regions. Participants were carefully screened for physical and mental health. In all subjects, the structured clinical interview
according to DSM-III-R (SCID) was applied. The first examination wave (t1)
was performed in 1994, t2 in 1998. Currently we are completing the t3
which was initiated in July 2005.
Results: Until now, 249 patients (121 females, 128 males) of the cohort
have been examined in T3. Mean age was 62.42.4 years at baseline (t1),
66.71.1 years at t2 and 73.90.84 years at t3. Lifetime prevalence rates
of MDD rose from 8.1% at t1 to 11.2% at t2. Preliminary analyses of the
current examination wave led to lifetime prevalence rates of 15.3%. The
point prevalence of MDD was 0.7%, 0.5% and 4.4% for t1, t2 and t3
respectively.
Conclusion: These preliminary results show an important increase in the
point prevalence rate of MDD in the third wave and emphasize the high
prevalence of affective disorders in elderly people. Since this condition
also affects general health and may contribute to an increased risk of
developing dementia, these results emphasize the clinical importance of
affective disorders in the elderly.
References: Stordal E, Mykletun A, Dahl AA.The association between
age and depression in the general population: a multivariate examination. Acta Psychiatr Scand. 2003 Feb;107(2):132-41.Voss E., Barth S.,
Pantel J., Martin M., Schmitt M., Schrder J. Age differences in prevalence
and course of major depression. Psychiatry Res, in press.
FC-14-02
Neurotrophic tyrosine kinase receptor type 3 as a gene
contributing to childhood-onset mood disorders
Cathy Barr
The Toronto Western Hospital, Genetics and Development, Canada
Yu Feng, Karen Wigg, Agnes Vetro, Eniko Kiss, Krisztina Kapornay,
Gabriella Darczy, Ildik Baji, Julia Gadoros, James Kennedy, Maria
Kovacs
Introduction: Major depressive disorder (MDD) is multifactorial disorder
with moderate heritability. Family and twin studies show the highest relative risk for MDD in families of probands with early age at onset and/or
recurrent episodes compared with the risk in the general population.
Chronic antidepressant treatment up-regulates the neurotrophin signaling pathway which is involved in neural plasticity and survival and deficits
in neural plasticity have been suggested to underlie the development of
depression. A genome scan of families multiply affected with recurrent,
early onset MDD by Holmans et al. (2004) revealed significant linkage on
chromosome 15q25.3-q26.2 (LOD = 3.73). One candidate gene located
in this 15q region, neurotrophic tyrosine kinase, receptor type 3 (NTRK3)
was particularly interesting because NTRK3 is a key gene in neural plasticity.
Method: We investigated the relationship of this gene to childhoodonset mood disorders (onset before age 14) in a sample of 607 families
with 725 affected children recruited from mental health facilities across
Hungary.
Results: The results of family based association studies of the NTRK3

gene show a significant association with 6 markers in our sample. The
most significant association was with the marker rs1369430 located in
intron 16.
Conclusion: These results support neural plasticity as a mechanism and
this gene specifically in the genetic susceptibility to mood disorders that
onset in childhood.
FC-14-03
The MTHFR gene, major depressive disorder and intermediate phenotypes
Daria Gaysina
Biochemistry and Genetics, Human Genomics, Ufa, Russia
Sarah Cohen, Farzana Hoda, Ania Korszun, Mike Owen, Nick Craddock,
Ian Craig, Anna Farmer, Peter McGuffin
Introduction: Indications that folate deficiency increases the risk for
depression have been obtained from biochemical and in vitro studies. The
enzyme 5,10-methylentetrahydrofolate reductase (MTHFR) is responsible
for the final step in the conversion of dietary forms of folate to 5-methyltetrahydrofolate. A single base mutation in the MTHFR gene (C677T)
results in the production of a mildly dysfunctional thermolabile enzyme.
The MTHFR 677T/T genotype and, to a lesser extent the 677C/T genotype, is associated with a significant elevation in the circulating concentrations of the homocystein and a decrease in serum folate concentrations, which may parallel a similar reduction in 5-methyltetrahydrofolate
in the CNS and may lead to a reduction in monoamine neurotransmitter
function and elevated risk of depressive disorder. Moreover, a recent
genome-wide linkage analysis for recurrent MDD has suggestive evidence
for linkage on chromosome 1p36 where the MTHFR gene is located. The
purpose of our study is to check the hypothesis that the MTHFR gene can
be involved in predisposition to special phenotypic subtypes of unipolar
depression based on personality traits measures.
Method: The sample of 1222 patients with diagnosis of unipolar depression/MDD (ICD10/DSMIV) recruited from 3 clinical sites: London, Cardiff
and Birmingham, UK (Men/Women = 381/841) and 833 control mentally healthy subjects (Men/Women = 371/464) was genotyped for the
C677T polymorphism. Such personality traits as Neuroticism, Extraversion
or Psychoticism were assessed in all subjects with the Eysenck Personality
Questionnaire (EPQ). We used Dominant 677T allele model to conduct
statistic analysis of our data with GLM and ANOVA (SPSS 13.0).
Results: There are not significant differences in genotype or allele frequencies between depressive patients and controls, neither in total samples, nor in females and males separately. No significant differences were
obtained in scores of three EPQ scales (Neuroticism, Extraversion,
Psychoticism) between patients-carriers of the T allele (+T group) and
homozygotes of the C allele (-T group) using GLM analysis.
Conclusion: In our study we failed to confirm the involvement of the
MTHFR gene in whole phenotype of MDD or personality traits in depressive subjects. We are currently testing the locus in relation to other intermediate phenotypes of MDD. This work was supported in part by INTAS
Postdoctoral Fellowship 04-83-3802.
References: Coppen, A., Bolander-Gouaille, C. 2005 Treatment of
depression: time to consider folic acid and vitamin B12. J Psychopharmacol 19, 59-65.
FC-14-04
The effect of mirtazapine on SSRI induced sexual dysfunction in depressive patients
Ali Bozkurt
Gulhane Askeri Tip Akademisi, Psikiyatri (Psychiatry), Ankara, Turkey
Tunay Karlidere, K. Nahit Ozmenler, Sinana Yetkin
Introduction: Sexual dysfunction is a common side effect of SSRIs.
Pharmacologic treatment of SSRI induced sexual dysfunction is studied
but the number of studies is limited. There are more studies of switching
to different agents than augmenting another agent. The aim of this study
is to analyze the effect of mirtazapine in SSRI induced sexual dysfunction
patients.
65
Method: 49 outpatients who were were in remission from major depressive disorder which were using SSRIs and experiencing sexual dysfunction
have been included in the study. All patients received mirtazapine 15 mg
and the medication has been increased to 30 mg after the first week.
Sexual functioning were measured with PRSexDQ of Montejo and
Golombock-Rust Inventory of Sexual Satisfaction (GRISS) before mirtazapine treatment and on week 1, 2, 4, 6, and 8 weeks during treatment.
Patients remission has been scored with Hamilton Rating Scale for
depression and has also been measured during the same days with other
scales. Patients who did not want to continue the study or who did not
come to appointments have been excluded. 33 patients (25 female, 8
male) have completed the study.
Results: All 33 patients maintained their remission from depression. 18
patients did have better sexual functioning and 15 did not according to
both PRSexDQ and GRISS. The mean and standart deviation of PRSexDQ
at the beginning and the week 8 is 9.87+/-2.39 and 5.94 ± 3.33
respectively. These scores are 47.19 ± 3.33 and 35.12 ±
15.59 in GRISS. The paired sample t-test analyzes is showing statistically
significant change in both scores.
Conclusion: Mirtazapine is an effective antidepressant for many patients
experiencing SSRI induced sexual dysfunction. It could be effective on sexual symptoms as an augenting agent due its postsynaptic 5HT2A antagonist activity.
References: 1. Gelenberg AJ, McGahuey C, Laukas C, Okayli G, Moreno
F, Zentner L, Delgado P. Mirtazapine substitution in SSRI-induced sexual
dysfunction. J Clin Psychiatry. 2000 May; 61 (5): 681. 2. Michelson D,
Kociban K, Tamura R, Morrison MF. Mirtazapine, yohimbine or olanzapine augmentation therapy for serotonin reuptake-associated female sexual dysfunction: a randomized, placebo controlled trial. J. Psychiatric
Research 2002 May-Jun; 36 (3): 147-52. 3. Farah A. Relief of SSRIinduced sexual dysfunction with mirtazapine treatment. J Clin Psychiatry
1999 Apr; 60 (4): 260-1.
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FC-18
Anxiety
T4 Anxiety
FC-18-01
Emotional numbing and salivary cortisol in male and
female Bosnian refugees with PTSD
Aida Spahic-Mihajlovic
University of Illinois, Department of Psychiatry, USA
John W. Crayton, E.J. Neafsey
Emotional numbing is an important symptom of PTSD, but it is not clear
whether it affects both positive and negative affect equally or not. To
address this question we administered Lang's Looking at Pictures test, in
which a series of pictures are rated on cartoon scales for valence (pleasant--unpleasant) and arousal (high--low), to 10 male and 11 female
Bosnian refugees suffering from PTSD (DSM-IV criteria) and to control
groups of 11 male and 10 female Bosnian refugees with similar trauma
exposure but without PTSD or any other major mental illness. All subjects
were also characterized using Foa's PTSD Symptom Scale and the
Hamilton Rating Scale for Depression. In addition, male subjects provided
salivary cortisol samples at 8AM on two consecutive days, with a 0.5 mg
tablet of dexamethasone taken at 11PM of the first day (between the two
saliva samples). The mean change in 8AM cortisol levels was not different
between the control (-0.067 ug/dl) and PTSD (-0.137 um/dl) male subjects
(t=-0.6277,df=12.92, p=0.54), in agreement with a recent review that
concluded that "no single pattern of HPA axis adaptation characterizes
posttraumatic stress disorder" (Rasmusson et al., CNS Spectr 8:651-6,
665-7, 2003). The mean valence ratings for unpleasant, neutral, and pleasant pictures of control males and females and of PTSD males were similar to normal ratings, but PTSD females rated neutral and pleasant pictures as significantly less pleasant than control females (ANOVA). Likewise,
the mean arousal ratings for unpleasant, neutral, and pleasant pictures of
both control males and females were similar to normals, with both
unpleasant and pleasant pictures rated more arousing than neutral pictures. In contrast, in both PTSD males and females pleasant pictures were
rated as almost completely non-arousing and significantly lower than
controls (ANOVA). Thus, in Bosnian refugees affective numbing is seen
primarily with pleasant or positive stimuli. The loss of "pleasant arousal"
in PTSD may correspond to the "reward deficit" seen in PTSD by Elman
et al. (Psych Res 135:179-183,2005), who found that male PTSD subjects
expended less effort thancontrols to extend the viewing time for pictures
of beautiful female faces.
FC-18-02
A single episode of acute psychosocial stress reduces cell
survival in adult hippocampal neurogenesis
Daniel Peterson
Rosalind Franklin University, Neuroscience, North Chicago, USA
Greg Hotsenpiller, Letia Peterson, Rosanne Thomas
Introduction: Factors modulating neurogenesis may contribute to the
pathophysiology of affective disorders, such as major depression.
Environmental stressors in animal models have been proposed to alter
neurogenesis, suggesting a mechanism for this contribution. The effect
of an acute psychosocial stressor on either proliferation or survival (immediate, short-, and long-term) was examined along with subsequent neuronal differentiation in the hippocampus of adult male Sprague-Dawley
rats.
Method: Subjects were exposed to a widely used social dominance paradigm that elicits behavioral and physiological responses to an acute psychosocial stressor. Naive young adult male rats (termed intruders) were
placed into a stable colony of retired breeder male rats from which a
young female had just been removed, resulting in the colony male rats
attacking the intruder rat. Intruder rats received injections of halogenated thymidine analogs at various timepoints relative to the stress experience and changes in the number of newly generated cells were assessed
by confocal stereology.
Results: We found that exposure to an acute psychosocial stressor at the

time of cell generation resulted in a decreased number of newly-generated
cells in the hippocampus. Using sequential thymidine analog administration to provide temporal discrimination of DNA replication, we demonstrate that short-term survival but not initial proliferation or immediate
survival was altered in response to stress. Furthermore, we determined
that stress experienced subsequent to proliferation also diminished longterm survival of cells.
Conclusion: An acute episode of a social stress produces long lasting
effects on the incorporation of new hippocampal neurons by reducing
their survival. This social dominance paradigm may mimic human relational stress more realistically than laboratory stressors and provides a socially
relevant model in which structural plasticity may contribute through alteration of neurogenesis.
References: 1) Peterson, D.A. (2002) Stem Cells in Brain Plasticity and
Repair. Current Opinion in Pharmacology 2:34-42. 2) Thomas, R.M. and
Peterson, D.A. (2003) A neurogenic theory of depression gains momentum. Molecular Interventions 3:441-444. 3) Thomas, R.M., Urban, J.H..
and Peterson, D.A. (2006) Acute exposure to predator odor elicits a
robust increase in corticosterone and a decrease in activity without altering proliferation in the adult rat hippocampus. Experimental Neurology
201:308-15.
FC-18-03
Metabolic syndrome in war veterans with post-traumatic
stress disorder with and without depression comorbidity
Miro Jakovljevic
Univ. Hospital Zagreb, Psychiatry, Croatia
Dragan Babic, Marko Martinac, Boris Maslov, Radmila Topic
Introduction: Post-traumatic stress disorder (PTSD), depression and
metabolic syndrome are growing public health problems in post-war
countries. High co-occurrence rates of PTSD and major depression have
been reported in different study samples. Understanding the co-morbidity
between PTSD, depression and metabolic syndrome has an important
clinical and theoretical issue. The objective of this study was to examine
the relationship between combat-related PTSD, co-morbid depression
and metabolic syndrome.
Method: Metabolic syndrome and its components as well as co-morbid
depression were investigated in 100 male war veterans with combat PTSD
and in 79 males who needed medical attention in dispensary of family
medicine.
Results: Metabolic syndrome according NCEP: ATP III was found in 25 %
of war veterans with PTSD patients. In 34.3 % of war veterans with comorbidity of PTSD and major depression in comparison with 6.1 % of
PTSD patients without co-morbid major depression, criteria for metabolic
syndrome were fulfilled. PTSD with moderate and severe co-morbid
depression was associated with higher rates of metabolic syndrome,
71.4% and 63.6% respectively.
Conclusion: PTSD and metabolic syndrome may be mediated by current
depressive symptomatology. Treatment of war veterans with PTSD should
address co-morbid depression and metabolic syndrome as well as the clinical features of PTSD.
FC-18-04
Genetic study of monoamine oxidase type B in combat
related posttraumatic stress disorder
Nela Pivac
Rudjer Boskovic Institute, Division of Molecular Medicine, Zagreb,
Croatia
Jelena Knezevic, Dragica Kozaric-Kovacic, Martina Dezeljin, Maja
Mustapic, Jasminka Pavelic, Dorotea Muck-Seler
Introduction: Several neurobiological systems are dysfunctional in posttraumatic stress disorder (PTSD). An enzyme monoamine oxidase (MAO)
occurs in two forms that differ in location, substrate and inhibitor specificities. MAO oxidizes different amines and neurotransmitters and regulates their concentration. Altered platelet MAO-B levels have been found
in different psychopathologies, suggesting that it may be a biomarker for
the particular disorders, personality traits and behaviors. The most com-
67
ANXIETY - Free Communications
mon polymorphism of MAO-B gene is an A to G change, present in intron

13. The hypothesis was that PTSD would be associated with altered
platelet MAO-B activity, due to the different distribution of the allele frequencies of the MAO-B genotype.
Method: Platelet MAO-B activity and MAO-B intron 13 polymorphism (a
G/A substitution) were determined in 103 war veterans with DSM-IV
diagnosed current and chronic PTSD, 41 combat exposed war veterans
who did not develop PTSD, and 242 healthy control male subjects. PTSD
patients were subdivided, according to the presence of psychotic symptoms (hallucinations or delusions on the psychotic module of the SCID, or
specific disturbance in form of thoughts by mental status examination),
assessed by the Positive and Negative Syndrome Scale, into subgroups of
28 patients with and 78 without psychotic features.
Results: One-way ANOVAs showed that veterans with psychotic PTSD
had significantly higher platelet MAO-B activity than veterans with or
without PTSD, or healthy subjects, and that smokers had significantly
lower platelet MAO-B activity than non-smokers in all groups. Two-way
ANOVAs revealed significant effects of smoking, or diagnosis and smoking, but no significant effect of genotype, or interaction between genotype, smoking or diagnosis, on platelet MAO-B activity. The allele frequencies of the MAO-B genotype (chi-square test) were similarly distributed
among healthy controls and veterans with or without PTSD and/or psychotic symptoms.
Conclusion: The MAO-B intron 13 polymorphism was not functional,
and did not affect platelet MAO-B activity, indicating that other polymorphisms should be assessed to determine functional significance and associations with different traits or disease. The results suggest that platelet
MAO-B activity, controlled for smoking status, might be used as a peripheral marker of the psychotic symptoms in PTSD.
68
CHILDHOOD & ADOLESCENT DISORDERS - Free Communications
FC-05
Childhood & Adolescent Disorders
FC-05-01
Comorbidity in autism spectrum disorders
Roberto Canitano
University Hospital of Siena, Child Neuropsychiatry, Italy
Valeria Scandurra
Autism spectrum disorders (ASD), namely Pervasive Developmental disorders as described in DSMIV, are characterized by three symptom domains:
impaired development of social interaction and reciprocity, communication difficulties affecting language and non verbal skills, repetitive
patterns of movements and behaviors which include restricted interests
and activities. A number of clinical manifestations that are not part of the
core symptom domains of Autism Spectrum Disorders are emerging over
time In some cases it is not straightforward to define these as additional
clinical manifestation because the phenomenology might be overlapping
with symptoms of Autism Spectrum Disorders (ASD) and it is unclear if
they stand for another disorder in its own right. Comorbidity in ASD
therefore is still awaiting for statistical and diagnostic validation in current
classification systems. It is important to underline that there is a mismatch
between the stability over time of the nuclear symptoms of ASD against
the variability of these associated symptoms. A developmental effect and
other unknown factors are probably at play and differences are found
according to the age band examined. Nevertheless on clinical ground different additional disorders need to be addressed. A strong vulnerability to
hyperactivity, stereotipies and tics/OCD is recognized in ASD. At present
there are several methodological flaws when evaluating the cooccurence
of symptoms in ASD and therefore the prevalence rates are unclear. In the
present study the main clinical problems and controversies on this issue
will be dealt with. Furthermore personal research data will be presented
regarding the following comorbidity issues: epilepsy in autism spectrum
disorders; tics and Tourette syndrome in autism spectrum disorders.
References: - Leyfer OT, Folstein SE, Bacalman S, Davis NO, Dinh E,
Morgan J, Tager-Flusberg H, Lainhart JE. Comorbid Psychiatric Disorders
in Children with Autism: Interview Development and Rates of Disorders. J
Autism Dev Disord. 2006 Jul 15; [Epub ahead of print]. - Matson JL,
Nebel-Schwalm MS. Comorbid psychopathology with autism spectrum
disorder in children: An overview. Res Dev Disabil. 2006 Jun 7; [Epub
ahead of print] - Canitano R, Vivanti G. Tics and Tourette syndrome in
autism spectrum disorders. Autism in press
FC-05-02
Ruptures in the communication between the autistic child
and its mother: Rethink the primary maternal concern
Celia Souza
Universidade Metodista, de Sao Paulo, Sao Bernardo do Campo, Brazil
Introduction: Recent studies on the autismo point with respect to a neuronal deficit in the calls neurons of mirrors, that would constitute one of
the neuronais bases of the social cognition, that] generates the establishment of our relations with the others [1. Winnicott emphasizes the paper
of the trauma, the privation and the intrapsquico conflict in the formation of the psicopatologia, attributing the health and the creativity to the
quality of the initial cares, primariamente for the mother. Supported in
the winnicottiana theory that sees in the autista the denunciation of the
imperfection of the primary concern materna (the capacity materna to
take care of of the baby in degree enough to prevent an agony) [2], and
worried in understanding what it is possible to a mother, in accordance
with its proper resources, in terms of minimizao of the effect of the
autismo, this objective work to argue the vicissitudes in the clinical evolution of autistas children from alterations of the primary concern materna,
through the psicanaltica intervention.
Methods: The delineation of the work is a documentary research, including consults books, periodic and the electronic article recovery in specific
databases in the WEB: PsycInfo, Vestibule of Pesquisa (CAPES), Dedalus,
BVS - Psi and Lilacs/Bireme, enclosing the period of 1949 the 2005.
Results: It was examined, in the consulted materials, the description of

some cases in treatment, to conclude the work.
Conclusion: Autistas children taken to the psycotherapy, had shown clinical evolutions in its state. The mother, perceiving the necessities of the
son, consequentemente will take it the treatment; this in makes them to
believe, that it has primary concern materna, that she is not failed in
this process and keeps it. Consequentemente, the child who the mother
does not lead to the psycotherapy, does not evolve, being able itself to
think that the parents had not had conditions of berar this child and
the mother, in special, has the primary concern materna diminished or
absent. However, how much the child will go or be able to evolve, it does
not depend only on the mother, the quality of the primary concern materna, nor so only of the support of the therapist. The autista child, as displayed in the work, presents a neuronal deficit, a deficiency of activity in
the neuron of mirrors, and this limitation must be considered.
References: [1] Thoret, H. New research suggests that a malfunctioning
mirror-neuron system could be behind the social isolation of autism. APA
Monitor on Psychology. v. 36, n. 9, October 2005. Disponvel em: . Acesso
em: 02 abr. 2006.
[2] Winnicott, D. W. (2000). Preocupao materna primria. In: Textos
Selecionados: da pediatria psicanlise. (D. L. Bogomoletz, trad.). Rio de
Janeiro, RJ: Francisco Alves (Trabalho original publicado em 1956).
FC-05-03
Cognitive function and skills performance of children with
attention deficit disorder
Hussein Abdeldayem
Alexandria University, Department of Pediatrics, Cairo, Egypt
Omayma Selim, Nabil Kitchener
Introduction: ADHD is considered as the most common neurobehavioral
disorder of childhood
Method: 1-Full medical history and clinical examination 2-Psychometric
study (Conners rating scale, Stanford Binnet, PAP, Adaptive behavior
assessment.) 3-Visual acuity and hearing assessment 4-Thyroid function
5-EEG
Results: The girls in the present study demonstrated more cognitive
impairments, particularly in the area of language function. All studied
case with ADHD showed normal thyroid function. The present study
showed higher abnormal EEG findings as compared to controls. The
present study revealed significant failure of academic achievement in
ADHD pupils as compared with normal controls. Whereas 87.5 %, who
showed poor scholastic achievement had ADHD, while only 14.3 % of
those who had excellent level had ADHD. IQ level of ADHD children in the
present study showed no significant difference from controls but perceptual reasoning showed a significant difference in ADHD children as compared with controls that might have a negative effect on the scholastic
achievement. deficits in intellectual functioning in ADHD children are best
accounted for by the multiple subtests grading and implications of
Stanford Binnet rather than a total IQ level. The studied ADHD children in
the present study also showed significant poor cognitive skills. Cognitive
difficulties would also explain the associated impaired academic performance. ADHD children in the present study showed a significant poor social
skills. Social skills defect might be because of frustrations and failures they
experience in academic performance which might cause problems in
their relationships with their teachers, peers, and families.
Conclusion: 1-Assessing the sub-areas and divisions of intellectual functions especially perceptual reasoning together with the functioning level
of all developmental skills were suggested. These findings, though are not
needed for diagnosis but are essential for full assessment, management
and follow up the effects of treatment strategy and interventions 2Implicating a four dimensional management program including: - Medical
treatment. - Cognitive training. - Behavioral and social therapy. - Parental
guidance and assurance.
References: 1-Goldman, L, Genel, M, Bezman, R, & Slanetz, P: Diagnosis
and treatment of attention deficit/hyperactivity disorder in children and
adolescents JAMA 1998, 279:1100 1107. 2-American Academy of
Pediatrics. Clinical practice guideline: diagnosis and evaluation of the
child with ADHD . Pediatr 2000; 105: 1158 3-Barkley RA, Fischer M, et al.
the adolescent outcome: an 8 year prospective follow up. J of Child and
Adolesc Psychiatr 2002 ; 29: 546-557
69
FC-05-04
Pediatric autoimmune neuropsychiatric disorders associated
with streptococcal infections (PANDAS)
Nabil Kitchener
Mataryia Teaching Hosp., Neuropsychiatry Dep., Cairo, Egypt
Introduction: A group of childhood-onset neuropsychiatric disorders has
been found to have a postinfectious autoimmune-mediated etiology,
related to infections with group A beta-hemolytic streptococci. This group
has been designated by the name: pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections(PANDAS). Some
clinical characteristics define the PANDAS group : presence of OCD and/or
tic disorder, prepubertal symptom onset (controversial as adult cases were
reported), sudden onset or abrupt exacerbations, association with neurological abnormalities during exacerbations (adventitious movements or
motoric hyperactivity), and the temporal association between symptom
exacerbations and streptococcal infections.
Method: Review of litrature and Documented case study was incited.
Results: The proposed post streptococcal inflammatory etiology provides
a unique opportunity for treatment and prevention, including immunomodulatory therapies such as plasma exchange and intravenous immunoglobulin.
Conclusion: Further research is required before such regimens can be
implemented in clinical practice. Until that time, children in the PANDAS
subgroup should be managed with standard therapies (e.g., serotonin
reuptake inhibitors and cognitive-behavior psychotherapy) and followed
prospectively for GABHS infections. Once an association between GABHS
infection and neuropsychiatric exacerbation is confirmed, aggressive
screening and early treatment for GABHS infections should then become
indicated adjuncts to the standard therapies.
References: 1.Kushner, HI, Kiessling, LS: Rethinking the diagnostic
boundaries of TS: The possible role of streptococcal antibodies in TS.
Tourette Syndrome Association, 1993; 4, 6. 2.Mattarazzo, EB: Tourettes
syndrome treated with ACTH and prednisone: report of two cases.
Journal of Child and Adolescent Psychopharmacology, 1992, 2, 215-226.
3.Swedo SE: Sydenhams chorea (SC): A model for childhood autoimmune neuropsychiatric disorders. JAMA, 1994, 272: 1788-1791.
FC-17
Childhood & Adolescent Disorders II
FC-17-01
Association between the vasopressin V1b receptor gene
(AVPR1B) and childhood-onset mood disorders
Cathy Barr
The Toronto Western Hospital, Genetics and Development, Canada
Emma Dempster, Karen Wigg, Eniko Kiss, Krisztina Kaparnai, Julia
Gadoros, Zsuzsanna Tamas, James Kennedy, Maria Kovacs, Agnes Vetro
Introduction: Disturbances in stress hormones have been implicated in
depression, in particular hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. Arginine vasopressin (AVP) plays a crucial role in modulating the HPA-axis under stress, and does so through a G-protein coupled
receptor, vasopressin V1b receptor (AVPR1b).
Method: To determine if genetic variation in AVPR1B could be contributing to vulnerability to depression we genotyped single nucleotide polymorphisms (SNPs) across this gene in sample of families with children
diagnosed with a mood disorder with onset before the age of 14. Six
SNPs were genotyped; 2 were novel non-synonymous polymorphisms and
the further 4 were constituents of a haplotype that has been previously
shown to be protective against depression. The sample was comprised of
378 Hungarian nuclear families ascertained through affected probands
with a diagnosis of a mood disorder.
Results: Two of the AVPR1B SNPs showed association individually
(Lys65Asn: c2 = 7.81, P =0.005; S4: c2 = 4.58, P=0.032), of particular
interest is Lys65Asn that causes an amino acid change in an intracellular
protein domain. Haplotype analysis demonstrated significant over trans-
70
mission of the most frequent haplotype (c2 =22.42 df3, P=0.00005).

Further, stratifying the sample by sex established that the association was
predominantly in affected females, which is consistent with previous
observations.
Conclusion: Our results support AVPR1B as contributing to depression,
particularly in females. Antagonists of AVPR1b exhibit antidepressant
qualities hence genetic variation in AVPR1B may have implications on the
HPA-axis dysregulation in depression.
FC-17-02
Rapid cycles in bipolar children and adolescents:
Hospitalization and treatment
USA
Introduction: Clinical literature refers to the rapid cycling in children and
adolescents with Bipolar Disorder (BD). It is useful to provide data on this
prevalent conception because rapid cycling in adults is associated with
more hospitalizations as a more treatment-resistant picture.
Method: The frequency of hospitalization and treatment of rapid cycles
(>=4 episodes per year) in Children and adolescents (<=18 y.o.) with BD
was examined using the Integrated Healthcare Information Services
(IHCIS) National Managed Care Benchmark. The database includes medical history for more than 30 million managed care lives, from more than
35 US health, HMO, POS and PPO plans, covering eight census regions
(mostly East coast) and patient demographics, including morbidity, age
and gender. Over 90% of patients had medical and pharmaceutical benefits. From June 30, 2000 to July 1, 2003, a total number of 8,129
patients (<=18 y.o.) with BD were identified (using ICD-9 codes).
Results: Among children and adolescents with rapid cycles, 58.6% were
females, 75.9% were between 12-17 y.o, and all had history of at least
one hospitalization for any reason. Children and adolescents with rapid
cycles (n=58) versus those without rapid cycles (n=8071) were differentiated in their hospitalization and treatment as follows: higher rate of hospital admission for any reason, for depression, and for medical conditions.
As we expected, they also exhibited a significantly higher use of antidepressants, antipsychotics and mood stabilizers.
Conclusion: Following the adult criteria for rapid cycles, our findings support that children and adolescents with rapid cycles require more pharmacological treatment than those with non-rapid cycles.
FC-17-03
Behavioral disorders in multiply handicapped Egyptian
children
Nabil Kitchener
Mataryia Teaching Hosp., Neuropsychiatry Dep., Cairo, Egypt
Magdy Khalaf, Ahmed Raouf, Nilly Nagy
Introduction: Behavioral disorders are not only very distressing to multiply handicapped patients and their families but also have a negative
impact on their learning at school or other facility, peer relationships and
social competence.
Method: A total of 3800 consecutive multiply handicapped patients
were retrospectively studied. Criteria for inclusion were regular follow-up
period for at least 24 months. Types and prevalence of behavioral disorders were correlated with the different forms of disabilities. Other factors
associated with mental retardation such as degree of disability, etiology,
correlation between degree of disability and percentage of behavior disorders; and types of behavioral disorders encountered were also analyzed.
Results: Follow-up ranged between 24 and 153 months (mean
61 months). Total group composed of 3800 multiply handicapped
patients, of which 94% suffered from mental retardation, 25% suffered
from cerebral palsy, 16% suffered from sensory deficits, and 29% suffered from epilepsy. The overall prevalence of behavioral disorders was
13% in the total group; (n=494 patients with behavioral disorders included pervasive developmental disorders(190), attention deficits with(152) or
without hyperkinesis (114) and disruptive behavior (253) disorders, those
include 38 patients with pure disruptive behavior, all patients with ADHD,
2 patients with ADD, and 61 patients with PDD). It was 13.8% in mental
retardation group; 4.3% in Cerebral palsy group; 3.8% in sensory deficits

group; and 16.3% in epilepsy group. In mental retardation group 1.3%
suffered from profound mental retardation, 5% suffered from severe
mental retardation, 36.6% suffered from moderate mental retardation,
and 57% suffered from mild mental retardation. Behavioral disorders are
more prevalent in the moderately retarded group(18%). The proposed
etiologies for disabilities were: Perinatal injury (41%); prenatal (37%);
Postnatal (9.5%); and Indeterminate (12.5%).
Conclusion: More attention should be paid to diagnose (detect and classify) and aggressively treat behavioral disorders by pharmacological, educational and environmental interventions.
References: 1-Einfeld SL, Tonge BJ. Population prevalence of psychopathology in children and adolescents with intellectual disability:
Irationale and methods. J Intellect Disabil Res 1996; 40: 91-98. 2-Emerson
E. Prevalence of psychiatric disorders in children and adolescents with and
without intellectual disability. J Intellect Disabil Res 2003; 47: 51-58.
3-Molteno G, Molteno CD, Finchilescu G, Dawes AR. Behavioural and
emotional problems in children with intellectual disability attending
special schools in Cape Town, South Africa. J Intellect Disabil Res 2001;
45: 515-520.
FC-17-04
Mental health of Malaysian teenagers. Is the situation the
same as seen in adults? Malaysian Mental Health Survey
(MMHS)
Saroja Krishnaswamy
Kavitha Subramaniam, Abdul Aziz Jemain, Tishya Indran, Abdul Hamid
Abdul Rahman, Vikram Patel
Introduction: Population based epidemiological studies accept people
aged 16 years old and above as adults. It is of note that those aged
between 16-19 years old are adolescents or teenagers at the brink of
adulthood, which is an important period of self-development. The expectations and responsibilities of this group are of difference from older
adults, moreover in a culture bound society like Malaysia, where the adolescents are still under strict control of parents or guardians. Could these
differences actually impact mental health situations of this group or
would it be the same as found in the adults? Objective: This study aims
to describe the prevalence of mental disorders and factors associated with
presence of mental disorders among the teenagers in the MMHS population.
Method: MMHS subjects aged 16-19 years old were included in this substudy. Descriptive statistics and logistic regression models were used to
determine prevalence and associated factors.
Results: Teenagers had a prevalence rate of 12% for mental disorders,
which is double the prevalence rate for the general population. Factors
found to be associated with presence of mental disorders among
teenagers were female gender (OR= 3.05, p=0.013), presence of serious
financial problem in the past year (OR=3.52, p=0.02), occurrence of serious illness or injury to parents or siblings (OR=6.15, p=0.001) and exposure to physical violence (OR=6.386, p=0.002). Some of the factors are
common between adults and adolescent in the sample.
Conclusion: The full paper will describe the methodology of the MMHS
study and provide explanatory model for these results.
71
NEURODEGENERATIVE DISORDERS - Free Communications
FC-07
Neurodegenerative Disorders
FC-07-01
Electrophysiological changes in the depressive symptoms
of Alzheimer's disease
Ezra Holston
University of California, School of Nursing, Los Angeles, USA
Introduction: Approximately 1.6 million Americans (7.2 million worldwide)
with Alzheimer's disease (AD) have depressive symptoms that do not fulfill the diagnostic criteria for depression. Neurobiological changes of
depressive symptoms have been associated with the progression of AD.
The proposed diagnosis depression of AD reflects the occurrence of
depressive symptoms in persons with AD. However, little is known about
the electrophysiological changes that may be associated with the depression of AD. Thus, the purpose of this descriptive, cross-sectional preliminary study was to retrospectively describe the abnormal electrophysiological changes in persons with AD and depressive symptoms to enhance
the diagnosing of AD.
Methods: The sample included 14 community residents (aged 51-89
years) with AD and depressive symptoms. Data were extracted from the
medical records and clinical EEG laboratorys database in a university hospital. Electrophysiological data were log-transformed and converted to
Z-scores with the NeuroGuide software for analysis and comparison to
NeuroGuides normative database. All data were analyzed with descriptive statistics and t-test, p.05. Topographic brain images were used to visually display the distribution of electrophysiological features.
Results: Participants (females = 8 (57%), males = 6 (43%)) had a mean
age of 70.12 8. Absolute and relative theta significantly increased (p =
.0001) from frontal to posterior regions. Age and gender had no significant effect on the electrophysiological features except for a significant
increase in absolute theta in the right lateral frontal regions (t-test =
-2.314 to -2.393, p = .034 to .039) in female participants. There was no
significant difference in the absolute and relative delta, alpha, and beta.
Conclusion: Depressive symptoms may be part of the constellation of
symptoms associated with AD, supporting the depression of AD. Further
analysis is warranted to further understand the abnormal electrophysiological changes, specifically theta, of depressive symptoms in AD to improve
the diagnosing of AD.
FC-07-02
Antagonism of organophosphate toxicity by donepezil
protected AChE activity against the almost total inhibition of AChE by

DFP. This was sufficient to completely prevent the induction of c-fos
mRNA in the brain by DFP.
Conclusion: Donepezil protected a significant proportion of AChE activity
against the almost total irreversible inhibition by DFP. The remaining AChE
activity effectively prevented the excessive excitation of the brain by DFP.
References: Janowsky DS, Davis JM, Overstreet DH. Antagonism of anticholinesterase (DFP) toxicity by donepezil plus scopolamine: a preliminary
study. Pharmacol Biochem Behav. 2004 Feb;77(2):337-43.
FC-07-03
Gender differences in brain reserve: An 18F-FDG PET study
in Alzheimers disease
Robert Perneczky
Technische Universitt Mnchen, Psychiatrische Klinik, Germany
Alexander Drzezga, Janine Diehl-Schmid, Yi Li, Alexander Kurz
Introduction: Neuropathological studies suggest that the association
between neurodegenerative brain damage and clinical symptoms is
stronger in women than in men and that therefore women are more likely
to express neurodegeneration as clinical dementia. The objective of the
present study was to test the hypothesis that cerebral metabolic deficits
due to neurodegeneration are more pronounced in men than in women
at the same level of clinical disease severity.
Method: 93 patients with mild Alzheimers disease (AD; 50 men, 43
women) and 16 age-matched healthy control subjects (7 men, 9 women)
underwent an extensive clinical and neuropsychological examination and
18F-FDG PET imaging at a university-based outpatient unit for cognitive
disorders. An analysis of covariance (with age, total score of the CERAD
neuropsychological battery, and years of school education as covariates)
was conducted in each study group to identify gender differences in glucose metabolism.
Results: Controlling for age, education, and clinical severity, cortical
regions were identified in the AD group, where glucose metabolism was
significantly reduced in men as compared with women. These regions
were located in areas typically affected by AD pathology (right inferior
frontal, superior temporal and insular cortex, and hippocampus).
Conclusion: These data suggest that the same clinical severity of dementia is associated with greater reductions in rCMRglc in men than in
women suggesting a greater degree of brain reserve in men.
FC-07-04
CSF tau protein differentiates geriatric major depressive
disorder from mild cognitive impairment
Peter Pregelj
Un. Psychiatric Hosp. Ljubljana, KOKP, Slovenia
Mehdi Saghafi, Marko Zivin, Robert Dolnicar
Peter Schoenknecht
Ruprecht-Karls-University, Geriatric Psychiatry, Heidelberg, Germany
Pablo Toro, Elmar Kaiser, Aoife Hunt, Johannes Pantel, Johannes
Schroeder
Introduction: Diisopropyl fluorophosphate (DFP) exerts its effect in the

brain by irreversibly inhibiting acetylcholinesterase (AChE)and results in
the overstimulation of central cholinergic activity. This study evaluated the
possible protective effects of reversible acetycholinesterase inhibitor
donepezil ( 2 mg/kg i.p.), on hypothermia, locomotor activity, AChE activity indicated by AChE staining and c-fos mRNA levels (marker of excessive
excitation) in the brains of rats treated with (DFP -1.3 mg/kg s.c.).
Method: Wistar rats were divided in subgroups: saline+H2O; saline+DFP;
donepezil+H2O sacrificed after 1 hour; donepezil+H2O sacrificed after 2
hours and donepezil+ DFP. Adjacent 10 mm cryosections processed for
AChE activity (Koelle hystochemical staining) and for c-fos mRNA levels
(radioactive method with 35S-labelled 45-mer antisense oligonucleotide).
Body temperature, locomotor activity and appearance of fasciculation
and oral dykinesia was recorded.
Results: 1.) Donepezil induces hypothermia per se 2.) Donepezil pretreatment partially protected locomotor activity against the almost total inhibition of locomotor activity by DFP 3.) Donepezil pretreatment partially
protected against appearance of fasciculations and oral dykinesia induced
by DFP 4.) DFP almost completely inhibited AChE and induced c-fos
mRNA in hippocampus and in striatum. 5.) Donepezil per se only partially and reversibly inhibited AChE activity. This was insufficient to induce
c-fos mRNA in the cerebral cortex. 6.) Donepezil pretreatment partially
Introduction: In Alzheimers disease (AD), an accelerated neurofibrillary

tangle formation is associated with increased tau protein release into the
cerebrospinal fluid (CSF). Significantly increased CSF tau protein levels
were found in patients at risk to develop AD indicating its potential as an
early marker. Though mild cognitive impairment in preclinical AD often
overlaps with depressive symptoms making early diagnosis difficult, to
date no CSF marker has been probed to support the differential diagnosis of geriatric major depressive disorder and mild cognitive impairment
eventually converting to AD.
Method: 81 patients with mild cognitive impairment (aging-associated
cognitive decline criteria), 54 patients with geriatric major depressive disorder and 27 cognitively healthy controls were included. In all participants, CSF levels of tau protein were determined by ELISA at baseline. All
patients were re-assesed clinically after a follow-up period of at least 12
month.
Results: During follow-up, 29% of the patients with mild cognitive
impairment but only one patient with geriatric major depressive disorder
converted to AD. CSF tau protein levels at baseline distinguished significantly between mild cognitive impairment, geriatric major depressive disorder and controls. Already at baseline converters to AD were characterized by significantly higher tau protein levels compared to any of the
other diagnostic groups.
72
Conclusion: CSF tau protein levels distinguish geriatric major depressive

disorder from preclinical AD and may predict conversion to AD in the
course of disease.
FC-20
Neurodegenerative Disorders II
FC-20-01
Sleep EEG in patients with Alzheimers and frontotemporal
dementia before and after long term treatment with
cholinesterase inhibitors
Rodrigo Rocamora
Tarragona, Spain
A. Thum, M. Giesler, A. Haag, S. Canisius, R. Dodel, J. C. Krieg,
U. Hemmeter
Introduction: Besides cognitive impairment, patients with dementia
commonly present with a disturbance of sleep wake rhythm. The most
robust polysomnographic finding in dementia is a reduction of REM-sleep
in Alzheimers dementia (AD). Cholinesterase inhibitors (Che-I) are the
treatment of choice in AD. Furthermore, sleep-EEG in frontotemporal
dementia (FTD) has been assessed only in one small study showing a disturbance of sleep continuity and a fragmentation of REM-sleep. The
objective of this ongoing study is to evaluate the effects of Che-I on sleepEEG variables, predominantly on REM-sleep in AD and FTD during longterm treatment.
Method: 13 patients with low to moderate dementia were examined. 7
patients had criteria for AD (5 men, 2 women, age 68.1 8.0 years,
MMSE 23.0 4.2) and 6 for FTD (4 men, 2 women, age 56.8 10.6
years, MMSE 23.4 3.7). A polysomnography was performed in all
patients 1) before therapy with a Che-I and 2) after 5-10 months, while
patients were on a monotherapy with a Che-I without further psychotropic medication.
Results: In all patients a severe sleep continuity disturbance was
observed. Patients with AD showed a more accentuated REM sleep reduction compared to FTD (REM%, AD 7.62 1.15 vs. FTD 16.04 9.41,
p<.05, U-test). FTD patients presented with an unstable and disrupted
REM-sleep. Treatment with Che-I did not improve sleep continuity variables. However, REM-sleep increased in patients with DAT (REM min.:
23.3 22.2 (t1) vs. 42.2 23.3 (t2), but not in patients with FTD (REM
min.: 67.0 51.5 (t1) vs. 62.1 41.9 (t2)). In FTD REM-sleep became
more stabilized reflected by a reduction of the number of sleep cycles.
Conclusion: The observed REM-sleep reduction in patients with AD compared to FTD may suggest that cholinergic neurotransmission is more disturbed in AD than in FTD. Long-term treatment with a Che-I monotherapy in patients with AD and FTD increases REM-sleep in AD and stabilizes
REM sleep in FTD. The observed increase of REM-sleep after long-term
treatment with Che-I in AD may reflect a pharmacological effect, but otherwise this increase may be related to the efficacy of anti-dementia treatment and course of the disease.
FC-20-02
Prevalence and natural course of aging-associated cognitive
decline (AACD) in a longitudinal population-based study
(ilse) in Germany: Preliminary results of the third wave
Methods: Within the population-based Interdisciplinary Longitudinal

Study on Adult Development and Aging (ILSE), neuropsychological
functioning was assessed in 500 community-dwelling subjects who were
born during 19301932 in Heidelberg and Leipzig. The participants were
carefully screened for physical and mental health in 1994 (t1), 1998 (t2)
and are being re-examined since July 2005 (t3). MCI was diagnosed
according to the "aging-associated cognitive decline (AACD)" criteria. All
diagnoses including conversion to AD were result of a consensus conference under supervision of senior consultant in old age psychiatry.
Results: Until now, 249 patients (121 females, 128 males) of the cohort
have been examined in T3. Mean age was 62.42.4 years at baseline,
66.71.1 years at t2 and 73.90.84 years at t3. At baseline, 13.4% of the
subjects fulfilled the AACD criteria. In t2 AACD prevalence rates rose to
23.6% and in t3 to 26.1%. In t3 there where 11 (4,4%) patients who fulfilled the criteria for an Alzheimers Disease (AD), and one (0,4%) for a
Vascular Dementia (VaD).
Conclusion: As indicated by the longitudinal population-based study
(ILSE), AACD is a frequent condition in the general population. While
AACD prevalence increased in the longitudinal course, a subgroup of the
AACD patients developed AD.
References: Levy R. Aging-associated cognitive decline. Int Psychogeriatr
1994;6:6368Schonknecht P, Pantel J, Kruse A, Schroder J. Prevalence
and natural course of aging-associated cognitive decline in a populationbased sample of young-old subjects. Am J Psychiatry. 2005
Nov;162(11):2071-7.
FC-20-03
The depression as a risk factor and complication for
Alzheimers Disease
Farhan Ul Haq Subhani
Bolan Medical College Quetta, Student, Pakistan
Aman Ul Haq Subhani
Introduction: Alzheimers Disease is most common form of dementia.
25% elderly depression patients develop Alzheimers disease. Over 80%
of patients with Alzheimers dementia develop noncognitive neuropsychiatric symptoms at some point during course of their illness and these
symptoms become sever as stage of disease advances. Depression affecting up to 50% of AD patients with lifetime symptoms in which 50%
patients suffer from major depression.
Method: It is a review to study pathophysiological effects and management of depression before and in Alzheimers disease.
Results: Approximately 25% or above elderly depressed person develop
Alzheimers disease in the upcoming few years. The patients complaining
memory failure and having a history of apathy are possibly at the early
stages of Alzheimers. The severity of depression increases as the
Alzheimers advances. The decreased level of brain-derived neurotrophic
factor (BDNF), in both Alzheimers disease and major depression is suggestive of molecular and chemical link between condition associated
combination. Molecular mechanism for decrease BDNF in brain has to be
studied with neuronal relational to treat it. Depressed patients are unable
to develop a positive affective bias of judgment for previously heard
melodies while Alzheimers patients could. As number of depressive
symptom increases, risk for Alzheimers disease increases by about 20%
for each. The depressive symptom in-patients of Alzheimers disease especially in developed world have a major cause that patients know, about
incurablity of disease.
Conclusion: These all suggest that depression is a major psychotic symptom in Alzheimers and may be a risk factor in old people for the disease.
Pablo Toro
Germany
P. Schoenknecht, J. Pantel, A. Kruse, J. Schroeder
Introduction: Little is known about prevalence and conversion from mild
cognitive impairment (MCI) to dementia of subjects at risk in the general
population.
73
FC-20-04
Wine and cognition
Roger Pinder
York, United Kingdom
Introduction: Alcohol is both a tonic and a poison. It all depends upon
the dose. However, there is substantial evidence that regular consumption
of moderate levels of alcohol (<25g daily) reduces the risk of coronary
heart disease by 35-40%, of stroke by 20-30%, and of type 2 diabetes
by 30%. Wine seems to be better than beer or distilled spirits.
Method: Population-based epidemiological studies have followed
cohorts of subjects over many years to correlate alcohol consumption and
cognition. Case control studies have also been performed. Similar studies
have focussed more specifically on alcohol consumption and the risks for
developing dementia.
Results: The risks of cognitive decline in older adults and of dementia are
substantially reduced by regular consumtion of alcohol, particularly (red)
wine. Female drinkers seem to benefit more than males in maintaining
cognitive function. The risks for cognitive decline and dementia follow a
J-shaped curve - moderate drinkers fare better than both abstainers and
heavy drinkers.
Conclusion: Regular consumption of red wine protects against cognitive
decline and dementia. Plausible biological mechanisms include antiinflammatory and antioxidant effects - for example, wine polyphenols may
inhibit development of, or even degrade, amyloid plaques. Wine and diet
may play important roles in preserving cognition.
References: Pinder RM, Sandler M (2004). Alcohol, wine and mental
health: Focus on dementia and stroke. Journal of Psychopharmacology
18:449-456.
74
PSYCHOTIC DISORDERS - Free Communications
FC-04
Psychotic Disorders
FC-04-01
Birth order - a culture dependent risk factor for schizophrenia?
Alexandra Strnad
Medical University Vienna, General Psychiatry, Austria
H. R. Chaudhry, S. Gschaider
Introduction: Factors like birth order, rank of birth, age difference
between siblings, family size, and parental age, are discussed as potential
risk factors for schizophrenia. In an earlier paper we identified the cultural
background as a variable, modifying the effect of the sib-position: Being
the first born predicted an elevated risk only for male Pakistanis, not for
female Pakistanis and also not for Austrians at all (Stompe et al.1999).
The aim of this study was to test the hypothesis whether or not first born
males with schizophrenia are over-represented in samples from traditional
societies.
Method: The position in the birth order of 78 patients with schizophrenia according to DSM-IV from Ghana, a West African country with hierarchical structured positional family systems was raised using a standardized questionnaire. The observed birth positions were compared with
the expected values by means of non-par chi-square tests.
Results: Like in Pakistan, being the first-born was a risk-factor for schizophrenia only for male patients from Ghana (first born: observed = 15,
expected = 6.1, intermediate: observed = 15, expected = 24.8, lastborn:
observed = 7, expected = 6.1; Chi-Square = 17; Asympt. Sig. = .000). All
other position in the birth order of male as well as of female patients did
not show statistically significant differences to the expected values.
Conclusion: Eldest sons have a prominent position in traditional patrilinear and patriarchal societies. They have more privileges but also more
responsibilities compared with their younger siblings, which may be an
excessive demand for individuals with vulnerability to develop schizophrenia. An alternative explanation for the unequal distribution of birth-order
in male schizophrenia subjects from Ghana might be a differential utilization of psychiatric facilities.
FC-04-02
Familial risk and prodromal features of psychosis in adolescents aged 15-16 years in the Northern Finland 1986
birth cohort
Pirjo Maki
University of Oulu, Department of Psychiatry, Finland
Jouko Miettunen, Anja Taanila, Irma Moilanen, Hanna Ebeling, Matti
Joukamaa, Erika Lauronen, Marjo-Riitta Jrvelin, Peter B. Jones, Markus
Heinimaa, Juha Veijola
Introduction: Subjects with family history of psychosis and with prodromal symptoms are at risk for schizophrenia. The aim was to study whether
adolescents with familial risk have more commonly prodromal features.
Method: Members (N= 9,215) of the Northern Finland 1986 Birth
Cohort, an unselected general population cohort, were invited to participate in a field survey conducted during 2001-2002. At the ages of 1516 years, the study included a 21-item PROD-screen questionnaire developed for screening prodromal psychotic symptoms with 12 specific questions for psychosis (Heinimaa et al. 2003). The scale measured symptoms
for last six months. The Finnish Hospital Discharge Register was used to
find out parental psychoses during 1972-2000.
Results: Of the males 24% and 37% of the females were screen positives for prodromal features at the age of 15-16 years. Of the offspring,
1.8% had parents with psychosis. The prevalence of screen positives was
26% in males and 36% in females with familial risk for psychosis.
Conclusion: Prodromal features of psychosis are prevalent in adolescence. It may be difficult to screen adolescent subjects at risk for developing schizophrenia with a questionnaire in a general population, especially
as these symptoms do not appear to be more common among subjects
with familial risk.
References: Jrvelin M-R et al. (1993) Br J Obst Gyn 100: 310-315

Heinimaa M et al. (2003) Int J Methods Psychiatric Res 12(2): 92-104
Acknowledgements: The Academy of Finland, the National Institute of
Mental Health, the Signe and Ane Gyllenberg Foundation and the Thule
Institute, Finland
FC-04-03
Estrogen, menstrual cycle phases, and psychopathology in
women suffering from schizophrenia
Niels Bergemann
University of Heidelberg, Dept. of General Psychiatry, Germany
Peter Parzer
Introduction: Estrogen has been hypothesized to have a protective and
antipsychotic-like effect in women at risk for schizophrenia. The aim of
the present study was to evaluate the association between menstrual
cycle and/or the estrogen levels and psychotic symptoms in a sample of
women with schizophrenia.
Method: 125 premenopausal women with schizophrenia and regular
menses were examined. The levels of 17-estradiol and other hormones of
the gonadal axis were assessed in the follicular, peri-ovulatory, and luteal
phases of the menstrual cycle. The effects of the menstrual cycle phase
and/or the estradiol level on The Positive and Negative Syndrome Scale
(PANSS) and the Brief Psychiatric Rating Scale (BPRS) scores were calculated by means of regression analyses.
Results: Significant improvement in psychotic, but not depressive symptoms was observed during the luteal phase, compared with other days of
the menstrual cycle.
Conclusion: The present findings indicate that estradiol may have specific
antipsychotic-like effect on the symptoms of schizophrenia. It thus may
be worthwhile to further investigate the therapeutic effect of estrogen.
FC-04-04
Weight issues in patients with first-episode schizophrenia
Kok Yoon Chee
University Malaya Medical C., Psychological Medicine, Kuala Lumpur,
Malaysia
Introduction: Body weight issue has always been a concern among
patients with schizophrenia especially those on atypical antipsychotics.
Allison et al. (2003) found 14% of 286 schizophrenia individuals being
treated with antipsychotic medications for 6 months had weight gain
more than 20 pounds. This is the first outcome study in Malaysia on firstepisode schizophrenia and related disorders in regards to their weight
issue and subjective quality of life.
Methods: I performed a cross-sectional study of patients diagnosed with
schizophrenia and related disorders by DSM-IV, and treated regularly
under routine clinical treatment setting for at least 12 months duration.
Data on first contact was taken from National Mental Health Registry for
Schizophrenia 2003-2005. Each subject was assessed with their weight,
height, and WHOQOL-BREF for their subjective quality of life.
Results: 124 patients were included in the study. Baseline weight was
57.712.9kg (mean BMI=21.54.1kgm-2) for patients taking typical
antipsychotics and 59.721.2kg (mean BMI=22.66.8kgm-2) for those
taking atypical antipsychotics. After treatment, weight has increased from
mean weight 57.92kg on contact to 65.46kg after treatment (p<0.005).
The group treated with typical antipsychotics has smaller mean weight
gain of 6.75kg compared to 10.0kg in the atypical antipsychotics group
but not statistically significant. The group taking atypical antipsychotics
after treatment presented with mean BMI 26.19kgm-2, which is considered class 1 overweight according to WHO. No relationship was found
between weight, weight gain or BMI with subjective quality of life.
Conclusion: Although no relationship with subjective quality of life was
noted with weight gain among patients, but the great weight gain and
the issue of overweight among patients with schizophrenia cannot be
overlooked as it predispose to greater medical co-morbidity. Asian population has a lower treshold for BMI in regards to cardiovascular diseases,
i.e. BMI between 22-25kg/m2 is considered a cutoff point for observed
risk (WHO, 2004). Therefore, regardless of type of antipsychotics, all our
patients do have at least observed risk for health due to overweight.
75
References: Allison D., Mackell J., McDonnell D.D., (2003).The impact of

weight gain on quality of life among persons with schizophrenia,
Psychiatr Serv 54:565-567.WHO Expert Consultation, (2004). Appropriate
body-mass index for Asian populations and its implications for policy and
intervention strategies, Lancet. 363:157-163.
FC-12
Psychotic Disorders II
FC-12-01
Flexibility and variability in lexicon usage among Yoruba
speaking Nigerian outpatients with schizophrenia: A controlled study
Abiodun Adewuya
OAUTHC, Dept. of Mental Health, ILESA, Osun State, Nigeria
Introduction: The studies on language dysfunction in schizophrenia are
few, inconclusive and have all been done in the western culture. There
may be cross-cultural and cross-lingual differences in problems with
speeches of patients with schizophrenia. This study aims to examine the
flexibility or variability in the use of words among a group of Nigerian
patients with schizophrenia compared with healthy controls.
Method: The spoken samples of 48 outpatients with schizophrenia and
48 matched controls were assessed using the mean segmental type token
ratio (MSTTR). The sociodemographic and clinical variables of the patients
with schizophrenia were also compared with their MSTTR scores.
Results: The MSTTR score for the patients with schizophrenia was significantly lower compared with those of healthy controls (P<0.001). The factors independently associated with lower MSTTR in patients with schizophrenia include younger age at onset of illness, presence of negative formal thought disorder and simple or hebephrenic subtype of schizophrenia.
Conclusion: Problem with flexibility and variability in lexicon usage
among patients with schizophrenia is a cross-cultural phenomenon. The
MSTTR may have value in predicting clinical judgements of thought disorder or in identifying deviant language. These may have broad potentials
for application in longitudinal and pathogenetic studies of schizophrenia.
FC-12-02
No evidence for a preferential transmission of the methylenetetrahydrofolate reductase 677T allele in families with
schizophrenia offspring
Jan-Willem Muntjewerff
GGz Nijmegen, Mental Health Institute, Netherlands
Mechteld Hoogendoorn, Maartje Aukes, Rene Kahn, Richard Sinke,
Henk Blom, Martin den Heijer
Introduction: The methylenetetrahydrofolate reductase (MTHFR)
677C>T polymorphism has been associated with an increased risk of
schizophrenia in various case-control studies. However, case-control studies are sensitive to population stratification, which is not an issue in familybased studies.
Method: We conducted a family-based study comprising 120 families
with a schizophrenic family member to explore the association between
the parental MTHFR 677C>T polymorphism and schizophrenia risk in offspring. In addition, a meta-analysis was performed using the available
studies with data on this subject.
Results: Transmission Disequilibrium Test (TDT) analysis showed no preferential transmission of the 677T allele from parents heterozygous for the
MTHFR 677C>T polymorphism to schizophrenia offspring (P=0.27). The
genotype relative risks were 1.43 (95% CI: 0.83-2.47) for the 677TT and
1.42 (95% CI: 0.54-3.78) for the 677CT genotype, relative to the 677CC
genotype. A meta-analysis using data from family-based studies, with a
total of 416 parent-child triads, yielded no evidence implicating the 677T
allele in schizophrenia risk (P=0.58). By applying a log-linear model, we
found no asymmetry within parental mating type.
76
Conclusion: Our data provided no evidence that transmission of the

MTHFR 677T allele is associated with schizophrenia risk. In addition, we
found no evidence that the maternal genotype influences the risk of having schizophrenia offspring substantially. Future studies should take into
account maternal environmental factors, such as nutritional deficiency,
because the phenotypic expression of the MTHFR genotype varies with
individual folate status. The same maternal genotype could have a variable outcome depending on the combination of severity of folate deficiency and the specific reproductive stage of the pregnancy in which
maternal folate status is low.
References: Muntjewerff JW, Kahn RS, Blom HJ, den Heijer M. 2006.
Homocysteine, methylenetetrahydrofolate reductase and risk of schizophrenia: a meta-analysis Mol Psychiatry 11:143-149.
FC-12-03
Metformin in the treatment of weight gain and metabolic
dysfunction during olanzapine administration: A doubleblind, placebo controlled study
Trino Baptista
Los Andes University, Physiology, Merida, Venezuela
Yamily ElFakih, Euderruh Uzcategui, Virginia Fernandez, Edgardo
Carrizo, Nairy Rangel, Mary Celvia Uzcategui, Ana Serrano, Tatiana
Galeazzi, Doritza Vargas
Introduction: Excessive weight gain, hyperglycemia and dyslipidemia are
often observed during olanzapine administration (1). The antidiabetic
metformin may counteract these side effects as it does in subjects with
type 2 diabetes or polycystic ovary. However, few studies have been conducted with this agent in psychiatric patients (2).
Method: In a double blind protocol, 80 patients with schizophrenia or
bipolar disorder receiving olanzapine for more than 4 consecutive
months, were randomly assigned to metformin (850-2550 mg/day, n = 40)
or placebo (n = 40). Body weight, body mass index, blood lipids, the
insulin resistance index (HOMA-R) and serum leptin levels were assessed
before and after treatment. Paired t-test were considered significant at
p < 0.05.
Results: Metformin was well tolerated at the maximal dose. Subjects in
the metformin group displayed a significantly decrease in body weight (p
= 0.04) and leptin levels (p = 0.03) while their HOMA-R remained stable
(p > 0.2). Body weight and leptin levels did not change in the placebo
group(p > 0.4), but the HOMA-R significantly increased (p = 0.02).
Conclusion: Metformin is a safe alternative to assist olanzapine-treated
patients to control body weight and carbohydrate metabolism.
References: 1) Newcomer JW. Second-generation (atypical) antipsychotics and metabolic effects: a comprehensive literature review. CNS
Drugs 2006; 19 (Suppl 1)1-93. 2) Baptista T, Martinez J, Lacruz A. et al.
Metformin for prevention of weight gain and insulin resistance with olanzapine: a double-blind placebo-controlled trial. Can J Psychiatry. 2006;
51192-196. Funded by FONACIT; G-2005-000-384 and Lilly Lab.
FC-12-04
Antipsychotics drug effect and cerebral activity in first
episode psychosis - SPECT assessment
Mihai-Dumitru Gheorghe
Euroclinic Hospital, Psychiatry, Bucuresti, Romania
Adriana Rambu
Introduction: Background: Therapeutical options in first episode psychosis (FEP) includ second genration of antipsychotics (SGA). If SGA are a
heterogenous pharmacological group and they have different mechanisms of action this means that their clinical effects must be different. This
thing must be evident at the patients with FEP to whom SGA treatment
is initialised. There is a few data which can prove that there are correlations between pharmacological profile, clinical effects and regional cerebral blood flow (rCBF) in FEP.
Method: 27 inpatients (18 males, 9 females;mean age 24.5 years) diagnosed with FEP according to DSM-IV-TR criteria and assessed with Positive
and Negative Syndrome Scale (PANSS). Single photon emission computed
tomography (SPECT) was performed before and after three months of
treatment with olanzapine (mean doses 12.5mg/day) in 10 patients with
predominantly positive symptoms, risperidone (mean doses 5.1mg/day) in

7 patients with predominantly negative symptoms, ziprasidone (mean
doses 120mg/day) in 5 patients with predominantly negative symptoms
and quetiapine (mean doses 540mg/day) in 5 patients with predominantly positive symptoms.
Results: SPECT assessment before the treatment revealed an important
low perfusion in the temporal and parietal left cortex and also in right
frontal cortex in 11 out of 14 patients with predominantly positive symptoms. In the patients with predominantly negative symptoms was
remarked a low perfusion in bilateral frontal cortex and especialy in the
left orbitofrontal cortex (9 patients). The cortical abnormalities observed
in patients at baseline persisted after treatment. In subcortical level
(16 patients) after treatment appears an increased perfusion in left striatal
ganglia indifferent to the type of psychotic symptomatology and SGA
use.
Conclusion: The data suggested the cortical abnormalities of perfusion
can be associated with the type of symptomatology. The subcortical
changes in striatal ganglia can be correlated with the antipsychotics use
but not with type of symptomatology or with one specific drug. It is difficult to establish a correlation between clinical features of FEP, the administration of one specific SGA and SPECT changes.
References: M.D. Gheorghe, A.V. Baloescu, G. Grigorescu, A. Petrescu,
Functional neuroimaging in first episode psychosis,Dialogues in Clinical
Neuroscience, 2005,7,1:50-52
FC-22
Psychotic Disorders III
FC-22-01
Insulin resistance in adolescent subjects at risk for psychosis
Juha Veijola
University of Oulu, Psychiatry, Finland
Pirjo Maki, Irma Moilanen, Anja Taanila, Jaana Laitinen, Tuija Tammelin,
Hannu Koponen
Introduction: It is unclear if there is a potential genetic vulnerability to
develop metabolic syndrome in subjects with psychosis. We were able to
study the signs of metabolic syndrome in subjects at risk for psychosis in
their adolescence.
Method: The Northern Finland 1986 Birth Cohort is a longitudinal oneyear birth cohort study from an unselected population (N=9,362). When
adolescents were 15-16 year-old they were asked to participate in a comprehensive field study. The procedure included fasting blood sample of
lipids, glucose and insulin, and measures of blood pressure and waist circumference. Subjects also completed a questionnaire concerning their
level of physical activity and daily dieting habits. Among participants of
the field study there were 117 subjects (51 boys) at risk for psychosis, ie
mother or father appearing in the Finnish Hospital Discharge Register
between 1972-2000 for any psychosis. Comparison group was altogether
6,470 participants (3,197 boys) without risk for psychosis.
Results: In boys at risk for psychosis the level on insulin was increased as
compared to those without risk for psychosis (mean level 12.5 mmol/L vs.
10.9 mmol/L). There were no other significant differences in the measures
of metabolic syndome between the two groups in boys or girls. Subjects
at risk for psychosis (both boys and girls) had somewhat lower level of
physical activity and poorer dieting habits compared to those without risk
for psychosis.
Conclusion: Increased level of insulin may be the first sign of metabolic
syndrome; our finding in boys suggests that there could be a a potential
genetic vulnerability to develop metabolic syndrome in subjects with
familial risk for psychosis. On the other hand the lower level of physical
activity and poorer dieting habits may as well explain the finding.
References: Henderson DC. Schizophrenia and comorbid metabolic disorders. J Clin Psychiatry. 2005;66 Suppl 6:11-20
FC-22-02
An evolutionary and phenomenological account of schizophrenia as a disorder of the evolved social brain
Jonathan Burns
University of KwaZulu-Natal, Dept of Psychiatry, Durban, South Africa
Introduction: Schizophrenia persists in our species despite fecundity disadvantages. This calls for an evolutionary approach to this disorder.
Furthermore, there is renewed interest in Bleulers affective dementia, or
the symptoms of social alienation, as core features of the disorder.
Finally, it appears that social selective pressures constituted the main driving force in human brain evolution. These three areas of enquiry share a
common ground that warrants exploration.
Method: Data from comparative primate and neuroanatomical studies as
well as from cognitive science and evolutionary genetics is integrated with
recent research on the social brain and dysconnectivity hypotheses of
schizophrenia.
Results: Schizophrenia represents a costly by-product of the evolved
social brain in Homo sapiens. Deficits in social cognition, and functional
and structural impairments of cortical circuits regulating social behaviour,
characterise schizophrenia and support the claim that it is primarily a disorder of the social brain. A recent imaging study (with DT-MRI) demonstrates structural dysconnectivity in frontotemporal and frontoparietal
cortical circuits in the disorder. These social brain circuits evolved in
ancestral hominids under social selective pressures related to group living.
This involved genetic alterations in the timing of neurodevelopment
(sequential hypermorphosis), a vulnerable process that was disrupted and
became manifest as the schizotypal phenotype. The phenotype exists as
a spectrum of cortical dysconnectivity thus accounting for the heterogenous presentation of schizophrenic illnesses.
Conclusion: Integrating our knowledge of human brain evolution into
current psychiatric research offers a new strategy for unravelling the complexities of mental disorders. In the case of schizophrenia, we find support for the notion of this illness as a disorder of the evolved social brain.
This model highlights the core social disability that defines the schizophrenias.
FC-22-03
Craniofacial evolution, heterochronic change and the origins of schizophrenia
Jonathan Burns
University of KwaZulu-Natal, Dept. of Psychiatry, Durban, South Africa
Introduction: Human brain evolution is characterised by greater than
expected enlargement of fronto-temporal (FT) and fronto-parietal (FP)
cortical circuits. Heterochrony, which refers to changes in the timing of
development, undoubtedly played a major role in sculpting the modern
human brain and face. Specifically, the mechanism sequential hypermorphosis - where there is progressive prolongation of each phase of development - appears to have been operative. The widened anterior skull
base and shortened lower face (in humans relative to hominid ancestors)
suggests this evolutionary mechanism. Expanding FT and FP cortical connections correspond to modern craniofacial findings - as the middle cranial fossa widened to accommodate cortical changes, the lower face
shortened. These evolutionary observations have relevance to our understanding of neurodevelopmental abnormalities in schizophrenia.
Specifically, anthropometric studies reveal craniofacial dysmorphologies.
Individuals with schizophrenia have widening of the anterior skull base
and shortening of the lower face.
Method: The author presents a study replicating these findings in an
African patient cohort and defends the following hypothesis: That the
schizophrenic phenotype represents an extension of the evolutionary
mechanism of sequential hypermorphosis responsible for craniofacial evolution in the human line.
Conclusion: Since this evolutionary mechanism relied upon changes in
the expression of genes regulating the timing of neurodevelopment, it is
to these regulatory genes that we should turn our attention in searching
for the genetic basis of schizophrenia.
77
BRAIN FUNCTION - Free Communications
FC-21
Brain Function
T8 Brain Function
FC-21-01
rTMS over the dorsolateral prefrontal cortex affects attentional control in depressed patients
Marie-Anne Vanderhasselt
Ghent University, Psychology, Belgium
Introduction: Depressed patients are impaired in their ability to shift the
focus of attention. These attentional control processes are thought to
depend on dysfunctions in the dorsolateral prefrontal cortex (DLPFC). It
has been proposed that this dorsal circuit plays an important role in the
interaction between emotional and attentional information processing.
Because of the different emphasis of fundamental cognitive neuroscience
research and clinical research on the application of repetitive Transcranial
Magnetic Stimulation (rTMS) on the DLPC as a therapeutic intervention,
surprisingly little research has been done on the effects of rTMS on cognitive functioning immediately after a single stimulation session in
depressed patients. Since the interplay between cognition and emotion
becomes ever more important in current models of depression, there is a
need for additional research is on cognitive functioning as a possible
marker of brain pathology in affective disorders.
Method: This study was conducted as a double-blind, placebo-controlled, crossover, within subjects design. Sixteen depressed patients performed a modified task switching paradigm with three conditions, before
and after receiving high frequency (HF) versus placebo rTMS over the left
DLPFC.
Results: One session of HF- rTMS over the left DLPFC had a specific beneficial effect on task switching performance whereas mood remained stable.
Conclusion: Antidepressant effects of rTMS could be related to the same
neurochemical changes that underlie cognitive functioning. Task switching performance may provide a unique window into the extent of antidepressant effects which can be considered as second-order long-term
effects possibly related to primary alternations in cognitive functioning.
References: Vanderhasselt, M.A., De Raedt, R., Baeken, C., Leyman, L.,
& Dhaenen, H. (2006a). The influence of rTMS over the left dorsolateral
prefrontal cortex on Stroop task performance. Experimental Brain
Research, 169(2), 279-282. Vanderhasselt, M.A., De Raedt, R., Baeken,
C., Leyman, L., & Dhaenen, H. (2006b). The influence of rTMS over the
right dorsolateral prefrontal cortex on intentional set switching.
Experimental Brain Research, 172(4), 561-565. Vanderhasselt, M.A., De
Raedt, R., Baeken, C., Clerinx, P., Leyman, L., & Dhaenen, H. (2007). The
influence of rTMS over the right dorsolateral prefrontal cortex on Stroop
task performance. Brain Research, in press.
FC-21-02
Brain 18FDG PET in panic disorder during the treatment
with CBT or antidepressants
Jan Prasko
Prague Psychiatric Center, 1st Clinical Department, Prague 8, Czech
Republic
Jiri Horacek, Richard Zalesky, Miloslav Kopecek, Tomas Novak, Beata
Paskova, Lucie Skrdlantova, Otakar Belohlavek, Cyril Hschl
Introduction: Twelve patients with panic disorder were studied with
[18F]-2-fluoro-deoxyglucose positron emission tomography (18FDG PET)
during resting state (condition of random episodic silent thinking, REST).
Method: After PET examination patients were randomly assigned to
either cognitive behavioral treatment group (6 patients) or antidepressants treatment group (6 patients). After 3 month 18FDG PET examination was repeated in both groups.
Results: Scores of psychopathology rating scales (CGI, HAMA, PDSS)
decreased in both groups. Changes of 18FDG uptake in pharmacotherapy group: decreases were found in a priori hypothesized regions in right
hemisphere, in superior, middle, medial and inferior frontal gyrus, superior and middle temporal gyrus, and increases were detected in a priori
hypothesized regions, mainly in left hemisphere in medial and middle
78
frontal gyrus, superior, middle and transverse temporal gyrus. Changes of

18FDG uptake in CBT group: decreases were found in a priori hypothesized regions of right hemisphere in inferior temporal gyrus, superior
and inferior frontal gyrus, and increases were detected in a priori hypothesized region, mostly in left hemisphere: inferior frontal gyrus, middle
temporal gyrus and insula.
Conclusion: Changes in brain metabolism after treatment either with
CBT or with antidepressants were similar in number of brain areas, with
prominent right-left difference. Supported by the project No. 1M0517
MZCR Czech Republic.
FC-21-03
Brain pathology in pedophilic perpetrators: Alterations of
brain structures framing reproductive behavior
Kolja Schiltz
Otto-von-Guericke-University, Psychiatry, Magdeburg, Germany
Joachim Witzel, Georg Northoff, Kathrin Zierhut, Udo Gubka, Hermann
Fellmann, Jrn Kaufmann, Claus Tempelmann, Christine Wiebking,
Bernhard Bogerts
Introduction: Pedophilic crime causes considerable public concern, but
hitherto no causative factor of pedophilia has been pinpointed (1). In the
past, etiological theories have postulated a major impact of environment
(2,3), but recent studies increasingly emphasized the role of neurobiological factors, too (4). However, the role of alterations of brain structures
crucial in the development of sexual behavior has not been systematically
studied in pedophilic subjects yet.
Method: Volume of the Amygdala and related structures playing a crucial role in the framing of reproductive behavior were assessed applying a
multimodal MR imaging approach in 15 pedophilic subjects and matched
controls. Characteristics of the sexual offenses and psychosocial adjustment were assessed too and related to the findings of the imaging analyses.
Results: Pedophilic offenders showed a significant decrease of amygdalar
volume on the right, corresponding to a visible enlargement of the anterior horn of the lateral ventricle as well as a reduction of local gray matter in the hypothalamus, septal regions, the substantia innominata, and
the bed nucleus of the stria terminalis. Smaller amygdalar volumes were
correlated with more uniform and focussed pedophilic activity.
Conclusion: Here we demonstrate alterations of structures that are critical for sexual development in pedophilic perpetrators, namely in the right
amygdala and bilateral closely related structures that constitute the medial extended amygdala (5). As regular development of sexual behavior during puberty requires the attribution of sexual valence to sensory cues (6),
a process mediated by the medial extended amygdala (7), it might be critically disturbed by these changes. Our findings suggests that the interference of a neuronal impairment with the maturation of sexual behavior
might prepare the grounds for pedophilia.
References: 1. Fagan, P.J., et al. JAMA 288, 2458-2465 (2002).
2. Dhawan, S. & Marshall, W.L. Sex Abuse 8, 7-15 (1996). 3. Hanson, R.
& Slater, S. Ann Sex Res 1, 485-499 (1988). 4. Blanchard, R. et al. Arch
Sex Behav 32, 573-81. (2003). 5. Newman, S.W. Ann N Y Acad Sci 877,
242-57 (1999). 6. Sisk, C.L. & Foster, D.L. Nat Neurosci 7, 1040-7
(2004). 7. Stark, C.P. J Gen Psychol 132, 207-24 (2005).
BRAIN FUNCTION - Free Communications
F-21-04
The impact of one session of repetitive high frequency
transcranial magnetic stimulation on mood and salivary
cortisol in healthy female subjects
Chris Baeken
AZ-VUB, Psychiatry, Brussels, Belgium
Lemke Leyman, Marie-Anne Vanderhasselt, Rudi DeRaedt, Hugo
DHaenen
Introduction: High Frequency repetitive Transcranial Magnetic
Stimulation (HF-rTMS) has yielded divergent results concerning its effect
on mood in normal volunteers. Methodological issues could have biased
earlier conclusions. Recently, we were unable to demonstrate mood
effects after one session of HF-rTMS on the left dorsolateral prefrontal
cortex (DLPFC). However, researchers have focused mainly on negative
mood changes, overlooking a possible positive mood induction. In this
study, we have tried to replicate our previous HF-rTMS findings on the left
DLPFC in a new (large) group of healthy female subjects, and we especially focused on positive mood influences. We also extended our former
research by stimulating the right DLPFC on, a different but comparable
(large) group of healthy female volunteers with the same HF-rTMS parameters. Importantly, previous studies in healthy volunteers demonstrated
the possible impact of HF-rTMS on the hypothalamic-pituitary-adrenal
(HPA) axis, such as cortisol secretion.
Method: Two sham-controlled, single blind, crossover studies were conducted. First, HF-rTMS on the left dorsolateral prefrontal cortex (DLPFC)
was performed in 28 young healthy female volunteers and mood assessment and appropriate salivary cortisol samples were collected. Second, in
a comparable, but different group of 26 healthy females, HF-rTMS was
performed on the right DLPFC. To detect any delayed mood changes,
assessments were also re-administered 30 minutes post HF-rTMS. Also
salivary cortisol samples were assessed before, just after and after 30 minutes of active and sham HF-rTMS. To examine subjective mood changes
we used Visual Analogue Scales (VAS), the Profile of Mood States (POMS),
and the Positive Affect and Negative Affect Schedule (PANAS), the latter
to assure assessment of positive emotions. To exclude individual anatomical differences, the left and right DLPFC were targeted under magnetic
resonance (MRI) guidance.
Results: We were unable to demonstrate immediate or delayed mood
changes after one single active HF-rTMS session on the left or right
DLPFC. One single session of HF-rTMS on the left DLPFC or on the right
DLPFC has no immediate nor delayed impact on the HPA-axis, as measured through saliva cortisol.
Conclusion: Although we controlled for several methodological problems known in rTMS mood induction studies, the hypothesis that one single
session of HF-rTMS at the left or at the right DLPFC can influence mood
or can attenuate the HPA-axis in healthy volunteers was not supported.
79
GENETICS - Free Communications
FC-10
Genetics
T9 Genetics
FC-10-01
Putative identification of susceptibility genes for autism
on 15q11-q13: Role of UBE3A and ATP10A
Guia Guffanti
University of Milan, Dept. of Biomedical Technologi, Italy
M. T. Bonati, Florinda Cavalleri, Francesca Cogliati, Margherita Marchi,
Luisa Strik Lievers, Ernesto Caffo, Lidia Larizza, Fabio Macciardi, Silvia
Russo
Introduction: The etiology of autism is still largely unknown despite our
current understanding from family and twin studies that genetics plays a
substantial role in the etiology of the disorder. Moreover, integrating data
from linkage studies and analyses of chromosomal abnormalities allow
identifying 15q11-q13 as one of the regions of particular etiopathogenetic
interest for autism and autism related disorders.
Method: In an effort to find the autism susceptibility genes potentially
harbored in this chromosomal region we have screened a set of markers
spanning two known imprinted, maternally expressed genes, UBE3A and
ATP10A, selected because they are both positional and candidate genes.
Results: We replicated evidence of Linkage Disequilibrium at marker
D15S122, located at the 5 end of UBE3A and originally reported by
Nurmi (2001). In addition, our analyses show also one significant haplotype that includes D15S122 at UBE3A and D15S1535 and SNP3 at
ATP10A. These findings are of particular interest considering that the
association of D15S122 has never been replicated until now and that
UBE3A is the gene responsible for the Angelmann Syndrome, that shares
neurological and behavioral abnormalities with the autism spectrum disorders.
Conclusion: Despite the limited power to detect genes of minor effect
with a low density SNPs, our data support a potential role of UBE3A in
the complex pathogenic mechanisms of autism. To strengthen our findings, we are currently genotyping a denser set of SNPs across the region
and using a larger sample, with the ultimate goal of identifying the specific polymorphism(s) responsible for the association.
References: Nurmi EL et al.(Mol Psy, 8:624-634, 2003) Vorstman JAS et
al. (Mol Psy 11: 18-28, 2006)
FC-10-02
Detection of oral cavity early injuries of eating disorders
(ED) and relation with biological markers and ED behaviours
Oscar Meehan
The Insitutute of Psychiatry, Eating Disorders, London, United Kingdom
Rene Panico
Introduction: Early symptom identification play a crucial role in prevention and early therapeutic interventions in any illness. The study aims at
identifying prevailing injuries and signs of oral mucous membrane and
their timing correlation with physical flag markers: vitamin A and
carotene plasma levels, amenorrhea, and eating disorder associated
behaviours: self injury, laxative and diuretic misuse, dehydration and
vegan diet.
Method: Case-control study of 65 untreated outpatients of a national ED
unit in Cordoba, Argentina, matched by gender and age with 65 healthy
controls. Diagnosis based on The Diagnostic and Statistical Manual of
Mental Disorders IV (DSM-IV) criteria for Anorexia and Bulimia Nervosa.
Prior to the study subjects and control group had a thorough oral cavity
examination at the Dental Medical School, a structured interview
designed to identify eating habits, weight control methods, and psychological symptoms related to ED, and the EDI-2 Scale. Inclusion Criteria:
DSMIV Eating Disorders Criteria for Bulimia (BN) and Anorexia (AN)
Exclusion Criteria: DSMIV Affective -, Psychotic -, Anxiety Disorders
Physical examination of the oral cavity was conducted following a comprehensive set of clinical procedure instructions and guidelines of the
Clinical Oral Cavity Examination Procedure and a dynamic examination of
swallowing movements.
80
Results: In the observed group 61 subjects had oral mucosa lesions

(94%) with 112 injuries in all; whereas less 18.5% of the controls had
them, 15 injuries in all, and a positive correlation between lesions and
newly onset ED symptoms, behaviours and biochemical evidence was also
found. Lesions: desquamative queilitis n 28, 43% - lip erythema n 28,
43% - , yellow palate n 22, 35% -, purpura n 17, 26% - bitten mucosa
n 12, 18% - palatal atrophy n 5, 8%. According to the Fishers Test there
is statistical significance @ p<0,005for each of the injuries in the observed
group and in the controls.
Conclusion: The description of these injuries and their correlation with
time of onset of ED has not been previously published in the medical literature.
References: Brown S., Bonifazi D.Z. An overview of anorexia and bulimia
nervosa and the impact of eating disorders on the oral cavity. Compend.
Contin. Educ. Dent. 14: 1954, 1956-1602, 1604-8. Hellstron I. Oral complications in anorexia nervosa. Scand. J. dent. Res. 1977: 85, 71-86
Russell G., Szmuckler G., Dare C., Eisler I. An evaluation of family therapy
in anorexia nervosa and bulimia nervosa. Arch. Gen. Psych. 1987; 44 (12):
1047-1056.
FC-10-03
Gene expression profiling in whole blood: Finding biomarkers for major depression
Witte Hoogendijk
VU University Medical Center, Psychiatry, Amsterdam, Netherlands
S. De Jong, J. van Zanten, B. W. J. Penninx, R. van Dyck, J. Smit,
G. Smit, S. Spijker, B. Ylstra
Introduction: Major Depressive Disorder (MDD) is a highly heritable disorder with a high lifetime prevalence. Polymorphic genes are more likely
associated with their most proximal gene product (i.e. gene-expression
profiles) than with more distal endophenotype such as cortisol levels or
man-made concept such as the depression syndrome. In order to gain
biomarkers for depression and to identify patient subclasses, we analyzed
the gene expression of whole blood samples.
Methods: The genome responsiveness at the individual genetic background of patients and controls was probed in 12 unmedicated wellmatched depressed cases and 11 healthy controls, as collected by the
Netherlands Study of Depression and Anxiety (NESDA). Whole blood samples were either kept at baseline (directly taken from the heparine collection tube) or challenged with lipo-polysaccharides (LPS; 10 ng/ml blood)
for 5 h. LPS-induced as well as base-line gene expression was determined by micro array analysis (Agilent whole genome arrays).
Results: LPS appeared to be a potent stimulus for blood cells, because
392 out of the 12,205 genes, that were analyzed, were regulated more
than 4-fold by LPS in all samples (i.e. 3.2% of total number of genes).
From these genes, the majority was up-regulated by LPS (288 out of 392).
Then, MDD-specific changes in LPS-induced gene expression were examined. From a set of 89 genes that were differentially regulated by LPS in
MDD cases versus controls (p<0.005), 23 genes seem able to completey
dissociate between healthy and disease state. The expression of these
disease-state specific genes will be verified using real-time quantitative
PCR.
Conclusion: Besides aiding to a more accurate diagnosis, pharmacotreatment and follow up strategies for MDD, analysis of gene expression
in whole blood samples might also be of use in identifying individuals at
risk for the (re)occurrence of depression. The next step will be to associate
this proximal endophenotype with polymorphisms that appear to be linked to depression in our genome-wide association studies.
GENETICS - Free Communications
FC-10-04
The role of Hypothalamic Pituitary Adrenocortical (HPA-)
axis in suicidal behaviour
Danuta Wasserman
Karolinska Institute, NASP, Stockholm, Sweden
Marcus Sokolowski, Vsevolod Rozanov, Jerzy Wasserman
Introduction: Twin studies, adoption, and family studies indicate the role
of genetic factors in suicidal behaviour. Moreover, the environmental factors such as negative life events may act as a significant contributor.
However, in many cases the exposure to the same environmental stress
does not result in increased suicidality pointing to a substantial genetic
contribution.
Method: The screening (S) and replication (R) samples of 259 and 266
trios (suicide attempter and both parents) were investigated for stressful
life events, personality traits and genotyped. Transmission disequilibrium
test analysis concerning relationships between the genetic markers and
suicide attempt were performed.
Results: Variation in the noradrenergic tyrosine hydroxylase gene was
associated with the angry/hostility personality trait and vulnerability to
stress. Genetic variation in the transcription factor T-box19, an upstream
regulator of the stress-related HPA-axis, showed linkage to a high
anger/hostility trait in suicidal offspring. Additional recent findings on
other markers of HPA-axis will be presented.
Conclusion: This is to our knowledge the first report on the association
of the angry hostility personality trait with genetic variation at the TBX19
locus, an important regulator of the HPA-axis. Other markers in the genes
regulated HPA-axis will be also of importance.
References: Caspi, A., et al., Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science, 2003.
301(5631):p. 386-9 D. Wasserman, et al., Genetic variation in HPA-axis
regulatory factor, T-box 19, and the angry/hostility personality trait. Genes
Brain Behav. 2006 Aug 7;
81
NEUROIMAGING - Free Communications
FC-09
Neuroimaging
T10 Neuroimaging
FC-09-01
Time series analysis of fMRI data using vector autoregression (VAR)
Wolfgang Tschacher
University of Bern, Psychiatry, Switzerland
Kerstin Sander
Introduction: Owing to recent technological advances with high-Tesla
MRI scanners, functional imaging of neural tissues with high resolution of
the temporal as well as spatial domains comes within reach. Thus, an
increasing demand for tools that allow the modeling and evaluation of
temporal data, i.e. data that carry sequential information, will likely result.
Method: Time series models based on such data can be computed to
study the dynamical connectivity of brain structures. We focused on the
method of vector autoregression (VAR) by which the strength of sequential interactions among multiple variables can be assessed. Such variables
may be the blood oxygenation levels of different regions in the brain
acquired by fMRI. The method of time series analysis was applied in data
sets from 20 subjects listening to auditory stimuli. These stimuli were of
an emotional nature (a person sobbing; a person laughing) and control
stimuli (backward-sobbing, backward-laughter, silence). Each data set
consisted of 207 consecutive MR scans. Models composed of 6 variables
(i.e., the following regions of interest: Amygdala left/right; Insula
left/right; Auditory cortex left/right) were computed.
Results: VAR of these variables resulted in a statistically significant model
of the sequential interactions among these variables in the sample. It was
found that the auditory cortex was directly influenced by the independent
variables (the auditory stimuli). Several further interactions were observed,
prominently among these an inhibiting effect of the auditory cortex on
the amygdalae.
Conclusion: In addition to these functional results, the methodological
merits and limits of the proposed method are discussed. It is concluded
that it is both a feasible and appropriate method to study and test
hypotheses about brain functioning on the basis of fMRI data.
FC-09-02
Serotonin1A receptor level affects neural activation
revealed by combining PET and functional MRI
Rupert Lanzenberger
Windischberger Christian, Mitterhauser Markus, Spindelegger
Christoph, Wadsak Wolfgang, Moser Ulrike, Stein Patrycja, Mien
Leonhard-Key, Holik Alexander, Kletter Kurt, Kasper Siegfried
Introduction: The neuromodulator serotonin inhibits long-term potentiation via serotonin1A (5-HT1A) receptors and increases postsynaptic
potentials indicating an important function in area-specific regulation of
synaptic plasticity and memory [1]. Here we used multimodal neuroimaging to investigate the influence of the 5-HT1A receptor on BOLD-associated neural activity.
Method: 30 healthy subjects (25.04.5y, 12 males) were measured with
both PET and fMRI. 5-HT1A receptor binding potential (BP) was quantified using the radioligand [carbonyl-11C]WAY-100635 and the SRTM (30
frames, 90min, 4.4mm FWHM, 35 slices). In fMRI (3T, EPI resolution
1.6*2.7*3mm, TE/TR=31/1000ms), subjects performed an emotion discrimination task (EDT, comparison of faces expressing different emotions)
and a sensorimotor control task (SMCT, matching geometrical objects) to
induce task-specific activation in limbic and visual areas [2]. Subject-specific parameter estimates calculated using SPM2 were extracted from limbic (amygdala) and visual (V1) ROIs. Regional 5-HT1A receptor BP of
8 ROIs were correlated with BOLD parameter estimates (contrast EDT to
SMCT) using Pearson`s correlation analysis (two-tailed, p<0.00625 threshold for multiple comparison).
82
Results: We found a negative correlation between neural reactivity in the

visual cortex and the orbitofrontal (r=-0.61, p=0.0003), anterior cingulate
(r=-0.51, p=0.004), and retrospenial cortices (r=-0.50, p=0.005), amygdala (r=-0.46, p=0.0098), insula (r=-0.46, p=0.010), and posterior cingulate cortex (r=-0.43, p=0.017), but not in the hippocampus or raphe
nuclei. There was no significant correlation between neural activity in the
amygdala and regional 5-HT1A receptor BPs.
Conclusion: The highly significant negative correlation between neural
activation and 5-HT1A receptor BP in several areas is consistent to the
inhibitory function of 5-HT1A receptors on glutaminergic neurons, the
major excitatory neurons. This mechanism might be relevant in the pathogenesis and treatment of depression, anxiety disorders and schizophrenia
showing altered 5-HT1A receptor levels [3].
References: 1. Edagawa Y et al. Brain Res,1999.827(1-2):225-8 2. Fisher
PM et al. Nat Neurosci,2006.9(11):1362-3 3. Lanzenberger R. et al. Biol
Psychiatry,2006 in press
FC-09-03
Development of brain function supporting excutive function in high-functioning autistic individuals
Beatriz Luna
University of Pittsburgh, Psychiatry, USA
Ran Liu, Krista Garver, Charles Geier, Nancy Minshew, John Sweeney
Introduction: Executive function, which supports goal-directed behavior,
is impaired in autism and is believed to be central to the neurocognitive
basis of this disorder 1-3. In healthy individuals, executive function
improves throughout childhood and reaches mature levels in adolescence
as prefrontal systems become more widely integrated with the rest of the
brain4. Our previous studies indicate that while individuals with autism
are impaired in the development of voluntary response inhibition, they do
show improvements throughout late childhood and adolescence that is
similar to typical individuals having important implications to windows of
plasticity5.
Method: In the present study, we performed a fast event related fMRI
study on 22 high-functioning autistic subjects and 22 healthy control volunteers 14-33 years of age during an oculomotor response inhibition
task. The antisaccade task is a widely-used task where subjects must suppress a tendency to make and eye movement to a suddenly appearing
peripheral cue and instead make a voluntary saccade to the mirror location.
Results: Results indicate that a large part of the circuitry known to support response inhibition is in place by adolescence in autistic individuals.
Differences in the recruitment of key regions including frontal systems
and in the efficiency of activating these regions, evidenced by comparing
time courses from functionally defined regions of interest, were present
in the autism group in both age groups. We also found similarities in
developmental transitions in the autism and typicals group from adolescence to adulthood suggesting preservation of key developmental
processes.
Conclusion: These studies indicate that while there are impairments in
neocortical circuitry throughout development in autism, there is also
important developmental progress suggestive of plasticity.
References: 1. Hill,E.L. Executive dysfunction in autism. Trends in
Cognitive Sciences 8, 26-32 (2004). 2. Minshew,N.J., Luna,B. & Sweeney,
J.A. Oculomotor evidence for neocortical systems but not cerebellar dysfunction in autism. Neurology 52, 917-922 (1999). 3. Luna,B. et al.
Neocortical system abnormalities in autism: an fMRI study of spatial working memory. Neurology 59, 834-840 (2002). 4. Luna,B. & Sweeney, J.A.
The emergence of collaborative brain function: fMRI studies of the development of response inhibition. Ann N Y Acad Sci 1021, 296-309 (2004).
5. Luna,B., Doll,S.K., Hegedus,S.J., Minshew,N.J. & Sweeney,J.A.
Maturation of executive function in autism. Biol Psychiatry (2006).
NEUROIMAGING - Free Communications
FC-11
Neuroimaging II
T10 Neuroimaging
FC-11-01
Dopaminergic modulation of cognitive performance: New
insights from 18F-FDOPA studies
Ingo Vernaleken
RWTH Aachen University, Department of Psychiatry, Germany
Yoshitaka Kumakura, Hans-Georg Buchholz, Thomas Siessmeier, Peter
Bartenstein, Paul Cumming, Gerhard Grfinder
Introduction: Molecular imaging, behavioural tasks, and animal data
suggest a linkage between cognition and dopamine transmission.
Furthermore, impaired cognitive performance is a key target in the treatment of schizophrenia. Although nearly all antipsychotic agents are
antagonizing D2-like receptors their effect on dopamine transmission,
storage capacity, and finally on cognition is not fully investigated, yet.
New positron emission tomography (PET) results - focussing on 18FFDOPA - will be presented that illustrate the dopaminergic modulation of
prefrontal cognitive functions.
Method: Nine healthy volunteers were scanned with 18F-FDOPA in drugfree baseline conditions and after three days of haloperidol treatment
(5mg/day). A continuous performance test (CPT), Stroop task, and a trail
making task (TMT) were administered in both conditions. The net bloodbrain clearance of 18F-FDOPA (K) in striatum, mesencephalon, and cortical areas was calculated by volume-of-interest analysis as well as the distribution volume of 18F-FDOPA in brain (VD) and the kloss.
Results: We found an increase of K after haloperidol treatment in caudate nucleus (NC) (K: 0.0030 0.0045 (mean SD); p=0.051) and
putamen (K: 0.0046 0.0053 (mean SD); P=0.051), as well as in thalamus, temporal cortex, and MPFC. The neuropsychological performance
changed only in outcome variables of sensitivity index significantly but not
in TMT, Stroop or %Hits in CPT. The change of CPT-hits was significantly
and negatively correlated with the baseline K in the putamen and amygdala (Putamen: r = -678; P = 0.045 / amygdala: -0.862; P = 0.003). The
change of CPT-sensitivity index was significantly correlated negatively
with baseline K in the NC and the amygdala (NC: r = -717; P = 0.030 /
amygdala: -0.867; P = 0.002). Also haloperidol induced changes in kloss
and VD correlated highly significantly with the baseline K.
Conclusion: It has recently been shown that dopaminergic transmission
correlates with cognitive performance of healthy subjects. The present
data suggest that the manipulation of cognition by antipsychotics is very
complex. So, not all subjects show an impaired cognitive performance.
Whether subjects showed a beneficial effects or impairment depends on
the baseline dopaminergic tone. This might be due to a reciprocal regulation of dopaminergic storage capacity and vesicular loss depending on
the initial K value. These data provide new insights in the regular physiology cognition.
FC-11-02
Interactions of SERT&BDNF: A complex genetic model of
depression
Lukas Pezawas
Medical University Vienna, Dept. of General Psychiatry, Austria
Venkatta Mattay, Joseph Callicott, Andreas Meyer-Lindenberg,
Daniel Weinberger
Introduction: BDNF and SERT are important genes in brain development
and function related to memory and emotion. Variation of the BDNF
(val66met) and SERT gene (5-HTTLPR) affects function of neurons, human
memory and fear behavior. Our previous work has shown that the S allele
of 5-HTTLPR affects the integrity, function and connectivity of a neural circuit linking amygdala and rostral anterior cingulate circuitry, a circuitry
related to anxious temperament and depression in the presence of environmental adversity. Additionally, we could show that val66met BDNF
affects the development and function of brain circuitries (hippocampus,
DLPFC) prominently implicated in working memory function. Convergent
evidence links BDNF to depression, such as data showing association of
the functional val66met BDNF polymorphism with increased risk for

depression, for temperamental traits related to depression, and associated
increases of BDNF expression after ECT and antidepressive SSRI treatment.
These data implicating a biological interaction of BDNF with 5-HTTLP
R-dependent signaling suggest a molecular mechanism that could support an epistatic interaction between the functional variants in these
genes in risk for depression. This possibility has been explored to a limited
degree in animals genetically engineered to be hypomorphic at both
genes. We hypothesized that the insufficient met BDNF allele does not
translate the S allele effect of 5-HTTLPR and therefore protects the subject from significant changes in subgenual cingulate and amygdala volume, which is reflected in functional connectivity data of this brain circuitry.
Method: We investigated magnetic resonance images (MRI) of 111 normal healthy volunteers without any psychiatric life-time history using optimized VBM, a sophisticated fully automated morphological imaging technique. Furthermore, functional and structural connectivity data were analyzed using SPM2.
Results: Consistent with our initial hypothesis, we found a significant
increased 5-HTTLPR S allele volume loss of the subgenual cingulate and
amygdala (p<0.001) in val/val BDNF carriers compared to met BDNF genotype. Structural connectivity and behavioral data reflected this relationship (p<0.001).
Conclusion: The met BDNF allele may be a protective genetic factor for
depression, because it only insufficiently translates 5-HTTLPR S allele
dependent structural and functional changes, which are related to
depression.
References: Pezawas, L. et al. J. Neurosci. 24, 10099-102 (2004).
Pezawas, L. et al. Nat Neurosci 8, 828-34 (2005). Hariri, A. R. et al.
Science 297, 400-3 (2002). Hariri, A. R. et al. J Neurosci 23, 6690-4
(2003). Egan, M. F. et al. Cell 112, 257-69 (2003).
FC-11-03
Integration of imaging and genetics: An analytical strategy
to perform genome-wide studies for Imaging Genetic
Phenotypes (IGPs)
Fabio Macciardi
University of Milano, Science and Biomedical Technol, Italy
Jessica Turner, James Fallon, Hal Stern, Steven G. Potkin
Introduction: Our goal is to develop novel approaches that address the
interplay of imaging and genetics, within the context of a specific disease.
Key to our approach is a general linear model (GLM) analysis of a quantitative imaging phenotype. The model can accommodate a range of factors expecting to affect the observed imaging activation (e.g., ethnicity,
behavior/performance): in the most basic form, the GLM is: Imaging
Phenotype = Overall Mean + Genotype Effect + Diagnosis Effect +
Genotype-Diagnosis Interaction Effect
Method: To perform a genome-wide analysis with 550,000+ SNPs, we
developed a method building on the work of Satagopan et al. (2004) and
modifying their approach to use the GLM summary test statistic on imaging phenotypes instead of traditional test statistics comparing allele frequencies across diagnostic groups.
Results: Our approach is to assume that a set T of the 500,000+ SNPs
are loci with true genotype-diagnosis interaction effects on the imaging
phenotype. The goal is to identify a subset t of these T true diseaserelated loci using the loci corresponding to the highest t test-statistics.
Note that the value of t is determined by considerations of power. The
power of the statistical strategy is defined as the probability that the
t highest test statistics correspond to t out of the T true disease (and
imaging) related loci. This power can be calculated by simulation as a
function of sample size, T and t, the minor allele frequencies in the
patient and control groups and the interaction effect size.
Conclusion: In an initial proof of concept investigation, we analyzed a
small sample of schizophrenics and matched controls, using specific IGPs
as quantitative phenotypes putatively related to brain areas implicated in
the disease and we found a set of SNPs satisfying the threshold criteria.
These SNPs point to several genes whose function is critically relevant for
brain functioning. A detailed analysis of our positive results also helped us
to identify functional cicuitries that may be altered in schizophrenia.
83
PSYCHOPHARMACOLOGY - Free Communications
FC-01
Psychopharmacology/Antidepressants
FC-01-01
Do effectiveness studies tell us the truth?
Hans Jrgen Mller
Ludwig-Maximilians-University, Dept of Psychiatry, Munich, Germany
The results of so-called effectiveness studies` have recently cast doubt on
the superiority of the second generation antipsychotics (SGAs). For example, the CATIE study found no major differences between the SGAs and
perphenazine, the chosen representative of the first generation antipsychotics (FGAs). The results of the CUtLASS study indicated that FGAs have
no disadvantages in terms of quality of life, symptoms or cost of care. A
third effectiveness study, by McCue et al., even found that haloperidol
(together with olanzapine and risperidone) was more effective than aripiprazole, quetiapine and ziprasidone in improving patients' mental status.
The methodological problems of each of these studies will be presented,
and accompanied by a discussion of the discrepancy between the results
of phase III efficacy studies and effectiveness studies.
FC-01-02
Escitalopram changes amygdala activation during emotional processing as revealed by pharmacological fMRI at 3T
Christian Windischberger
Medical University of Vienna, Department of Psychiatry, Wien, Austria
Rupert Lanzenberger, Susanne Friedreich, Christoph Spindelegger,
Alexander Holik, Patrycja Stein, Ulrike Moser, Florian Gerstl, Ewald
Moser, Siegfried Kasper
Introduction: Hyperactivity of limbic areas including the amygdala has
been demonstrated in patients suffering from anxiety disorders [1].
Accordingly, it can be hypothesized that the anxiolytic effect of SSRIs is
based on a medication-dependent change in responsivity to emotional
stimuli in limbic areas. Here we used functional magnetic resonance imaging (fMRI) to investigate whether SSRI administration may cause changes
in brain activation during emotion processing.
Method: Ten healthy male subjects (25.33.7 yrs., mean ageSD) were
investigated using a randomized, cross-over, placebo-controlled, doubleblind design. Each participant underwent three fMRI sessions with an
interscan interval of ~30 days. Study medication (either 10mg escitalopram/d, or 20mg citalopram/d, or placebo p.o.) started 10 days prior to
the fMRI scans. MR measurements were performed at 3 Tesla (Bruker
Medical, Germany) using a high-resolution protocol (EPI inplane resolution 1.6*2.7mm, 10 axial slices with 3mm thickness oriented parallel to
the AC-PC plane, TE/TR=31/1000ms) optimized for imaging of the amygdala region [2]. Subjects performed a facial emotion discrimination task
and a sensorimotor control task (matching geometrical objects) adapted
from [3]. Preprocessing and analysis was performed in SPM2, including
slice-timing correction, realignment, normalization to standard space and
spatial smoothing (FWHM=9mm). For first-level analysis, a fixed-effects
model was setup for each participant comprising all three scanning sessions. Using a regions-of-interest (ROI) approach, two ROIs (amygdala
region, primary visual cortex) were defined. Parameter estimates were
extracted in each subject and included in one-factorial ANOVAs (factor
medication, contrast EDT vs. control task) and post-hoc t-tests were performed.
Results: ANOVA revealed a significant effect of medication on amygdala
activation (F=3.8, p=0.034). Post-hoc t-tests showed that escitalopram
caused significantly decreased amygdala activation when compared to
placebo (p=0.042) or citalopram (p=0.046). No significant activation differences were found between citalopram and placebo. There was no significant main effect of medication on activation in the primary visual cortex
(F=0.2, p=0.80, ANOVA).
Conclusion: Escitalopram reduced amygdala activation in healthy subjects during processing of emotional stimuli. A similar task-specific effect
was not found in the primary visual cortex arguing against medication-
84
induced changes in attention or vigilance. These findings are consistent

with a change of responsivity in limbic areas due to escitalopram administration.
References: 1.Davidson et al. CurrOpinNeurobiol 1999 2.Robinson et al.
Neuroimage 2004 3.Hariri et al. Science 2002
FC-01-03
Putative mechanism of augmentation of antidepressant
response by atypical antipsychotic drugs
Eliyahu Dremencov
University of Ottawa, Inst. of Mental Health Research, Canada
Mostafa El Mansari, Pierre Blier
Introduction: Atypical antipsychotics risperidone and olanzapine were
previously shown to reverse the escitalopram-induced inhibition of norepinephrine (NE) neuronal firing activity (Seager et al., Psychopharmacol
181:126, 2005; Dremencov et al., Biol Psychiatry Epub 2006 Aug 23).
Thus, non-response to selective serotonin (5-HT) reuptake inhibitors
(SSRIs) in some depressive patients may be explained by a decreased NE
tone and the beneficial effect of atypical antipsychotics by its reversal. The
present study aimed to determine if paliperidone (the 9-OH metabolite of
risperidone) exerts distinct effects on 5-HT and NE neuronal activity from
those of risperidone.
Method: Extracellular single unit recordings were carried out from rat
dorsal raphe and locus coeruleus under chloral hydrate anesthesia
(400 mg/kg, i.p.).
Results: It was found that the acute administration of risperidone
(0.4 mg/kg, i.v.) produced a robust inhibition of firing rate of 5-HT neurons. This inhibition was partially reversed by the NE reuptake inhibitor
desipramine (5 mg/kg, i.v.) or by the 5-HT1A antagonist WAY 100635
(0.1 mg/kg, i.v.) and completely reversed when both WAY 100635 and
desipramine were given. The same degree of inhibition of 5-HT neurons
was observed after 2 or 14 days of risperidone administration
(1 mg/kg/day, s.c.). However, 1 mg/kg/day of paliperidone did not alter
the firing rate of 5-HT neurons neither after 2 or 14 days of administration.
Paliperidone, as observed with risperidone, did not alter the firing rate of
NE neurons by itself but reversed the escitalopram-induced suppression of
NE neuronal firing after 2 or 14 days of co-administration. However, differently from risperidone, paliperidone co-administered with escitalopram
did not elevate the firing rate of NE neurons above the value of control
animals after 2 days of administration.
Conclusion: The capacity of paliperidone to reverse the SSRI-induced
inhibition of NE neuronal firing rate, without decreasing of 5-HT neuronal
activity, suggests that paliperidone may be beneficial in SSRI-resistant
depression.
References: Supported by Janssen Pharmaceuticals.
FC-01-04
Social isolation enhances the effects of 5-ht1a agonist, 8oh-dpat in the rat forced swimming test
Noppamars Wongwitdecha
Walailak University, School of Medicine, Nakhon Si Thammarat, Thailand
Introduction: Social isolation after weaning has been reported to have
profound effects on behaviours, neurochemistry of the adult animals and
modified the responsitivity to psychoactive drugs (1-3). The present experiments investigated the effects of a selective 5-HT1A agonist, 8-hydroxy2-(di-n-propylamino) tetralin (8-OH-DPAT) on the forced swimming test,
and compared the effects of acute and chronic treatment of 8-OH-DPAT
on this behaviour in isolation and socially reared rats.
Method: Male Wistar rats were obtained from weaning, and housed
either alone (isolation rearing) or in groups of six rats/cage (social rearing)
for five weeks. These rats were tested for their sensitivity to 8-OH-DPAT
using the forced swimming test (4).
Results: Pretreatment of 8-OH-DPAT (0.1, 0.25, 0.5 and 1 mg/kg s.c., 24
h and 1 h before a 5 min test) in socially reared rats produced a dosedependent reduction of immobility and elevation in struggling compared
to saline treated group. Acute administration of 8-OH-DPAT (0.5 mg/kg
s.c. 24 h and 1 h before a 5 min test) significantly decreased immobility
and increased struggling (P<0.01) in both isolation and socially reared rats
PSYCHOPHARMACOLOGY - Free Communications
compared to saline treated group. These effects were greater in isolation

reared rats than socially reared rats. In chronic experiments, in which all
rats were repeatedly injected with either 8-OH-DPAT (0.5 mg/kg s.c.) or
saline for 7, 14 and 21 days, the 8-OH-DPAT treated rats (both isolation
and socially reared rats) still showed significantly less immobility and more
struggling than saline treated groups; however, there was no significant
difference between isolation and socially reared rats.
Conclusion: The results showed that isolation rearing enhanced the
responsitivity to acute administration of 8-OH-DPAT. However, this difference was not seen after chronic 8-OH-DPAT treatment. These results indicate that isolation rearing causes increased 5-HT1A receptor function but
this effect is only observed after acute 8-OH-DPAT administration.
References: 1. Wongwitdecha, N., Kasemsook, C., Plasen, S. (2006)
Behav. Brain Res. 167, 232-236. 2. Wongwitdecha, N., Panya, P., Yoopan,
N., Ritilert, P. (2006) Int. J. Neuropsychopharmacol. 9 (Suppl 1), S174.
3. Wongwitdecha, N., Marsden, C.A. (1996) Brain Res. 715, 119-124.
4. Porsolt, et al. (1978) Eur. J. Pharmacol. 47, 379-391.
FC-15
Psychopharmacology
FC-15-02
Triggering factors for one-trial tolerance in the four-plate
test-retest
Michel Bourin
Faculte de Medecine, Pharmacology, Nantes, France
B. Petit-Demoulire, M. Hascot
Introduction: One-trial tolerance to benzodiazepines has been described
with rodents in the elevated plus-maze (EPM). This loss of effect of drugs
with experienced animals is an interesting tool to analyze mechanisms of
action of these treatments. In the present study, we have compared testretest paradigm in the four-plate (FPT) and one-trial tolerance. We have
considered the behaviour of mice through two drives: exploration and
fear; in order to discover the main causes of the loss of effect of diazepam in FPT. In parallel, we have studied the effect of DOI, a selective
5-HT 2A/C agonist, which keep its anxiolytic-like effect in trial 2.
Methods: Nave swiss mice were exposed to FPT with or without electric
punishments (Experiment 1-2) or modified FPT (Experiment 3) or EPM
(Experiment 4). During the second exposure, 24 hours later, mice were
injected i.p. with drugs.
Results: Removing punishments in trial 1 is not sufficient to cancel the
loss of effect of diazepam, but a modified aversive environment in trial 1
recovers its anxiolytic-like effect in trial 2. Exposure to EPM then FPT does
not trigger a loss of effect of diazepam.
Conclusion: The loss of effect observed with diazepam in trial 2 with FPT
can be considered as a one-trial tolerance phenomenon. Punishment is
not the triggering factor; whilst knowledge of the environment seems to
be the main reason in the appearance of one-trial tolerance to benzodiazepines. FPT may be a good candidate to study one-trial tolerance because punishments act as a potentiator in this model.
References: Hascoet M, Bourin M, Couetoux du Tertre A (1997) Influence
of prior experience on mice behavior using the four-plate test. Pharmacol
Biochem Behav 58: 1131-1138Ripoll N, Nic Dhonnchadha BA, Sebille V,
Bourin M, Hascoet M (2005) The four-plates test-retest paradigm to
discriminate anxiolytic effects. Psychopharmacology (Berl) 180: 73-83
FC-15-03
A comparison of quetiapine and risperidone in elderly
patients with BPSD
Michael Rainer
Danube Hospital, Psychiatric Department, Vienna, Austria
Introduction: The only atypical antipsychotic to be indicated for the
treatment of BPSD is risperidone, and it is only indicated in Canada,
Europe and Australia. This ist the first head-to-head study designed to
investigate the efficacy, cognitive function and tolerability of quetiapine in

comparison with risperidone in dementia-outpatients aged 55-85 years
experiencing BPSD.
Method: Eight-week, investigator-blinded, randomised study of 72 outpatients (55-85 years) with BPSD who received flexibly-dosed quetiapine
(50-400mg/dy) or risperidone (0.5-2mg/day). Primary efficacy variable:
Neuropsychiatric Inventory (NPI) Parts I, and II (sum of scores). Secondary
endpoints included Mini-Mental-State Examination (MMSE), extrapyramidal symptoms (EPS; Simpson-Angus Scale [SAS] and adverse events (AEs).
Results: Sixty-nine out of 72 patients were considered evaluable (three
patients were outside inclusion criteria), four patients discontinued (three
due to AEs: quetiapiene [2], risperidone [1]; one lost to follow-up);
65 patients received quetiapine (n=34; mean dose 77 40mg/day) or
risperidone (n=31; mean dose 0.9 0.3 mg/day).NPI scores improved significantly from baseline to Week 8 with quetiapine (Part I, 25.56-17.52;
Part II, 30.17-27.73) and risperidone (Part I; 25.74-16.58; Part II, 30.3026.71) [all P < 0.05 vs. baseline], with no significant differences between
groups. MMSE scores remained stable from baseline to Week 8 with quetiapine (18.50-18.47) and risperidone (18.00-18.65). Both treatment
groups were similar on safety measures, including EPS (measured using
the SAS). 57.9% and 44.1% of quetiapine- and risperidone-treated
patients, respectively, experienced mild or moderate AEs. Four patients
experienced serious AEs (quetiapine, 3; risperidone, 1); none were considered treatment-related. There were no cerebrovascular AEs or deaths.
Conclusion: Both treatments were equally effective against BPSD in elderly outpatients, were well tolerated and did not impair cognition.
References: M. Rainer et al: Effect of Risperidone on Behavioral and
Psychological Symptoms and Cognitive Function in Dementia. J Clin
Psychiatry 62:11, November 2001
FC-15-04
Quetiapin augmentation in severe obsessive compulsive
disorder (OCD)
Andreas Kordon
University of Luebeck, Psychiatry / Psychotherapy, Lbeck, Germany
U. Voderholzer, B. Zurowski, K. Wahl, N. Koch, F. Hohagen
Introduction: Although patients with obsessive-compulsive disorder
(OCD) benefit from treatment with serotonin reuptake inhibitors (SRIs), it
is estimated that 40 to 60 % of the patients remain unimproved. The
objective of the study was to evaluate the efficacy and tolerability of quetiapine or placebo added to baseline treatment of SRIs (=SSRI/clomipramine) for the treatment of OCD in severely ill adult subjects. Patients received treatment for 12 weeks. The total Yale-Brown-Obsessive-CompulsiveScale (Y-BOCS) score was the primary efficacy parameter. A responder
was defined as having a decrease of 30% or more in the total Y-BOCS
score.
Methods: 39 patients (18 men / 21 women, mean SD age = 34,2 9.2
years) with primary OCD according to DSM-VI criteria participated in a
12-week, double-blind, placebo-controlled trial. They were randomly
assigned to dosages titrated upward to 400 mg/day of quetiapine (N=19)
or to placebo (N=20) in addition to their SRI treatment. During the continuation phase (8 weeks) subjects received different dosages between 400
and 600 mg/d depending on clinical response. At entry, all patients were
unresponsive to courses of at least 12 weeks treatment with SRIs in
defined minimum dose.
Results: Intent-to-treat, last-observation-carried-forward analysis
demonstrated a mean SD decrease in Y-BOCS score of 5.2 5.4 in the
quetiapine group and 3.9 4.9 in the placebo group. The analysis of
treatment effects between the two groups shows no significant difference (differences of least square means = -1.43; p = 0.40). There were
no significant group differences in any of the other self rating scales (Beck
Depression Inventory (BDI); Patient Global Impression Scale (PGI); Quality
of Life (SF-36)) or clinician administered rating scales (Hamilton
Depression Rating Scale (HAM-D); Clinical Global Impression Scale (CGI);
Egosyntonic Scale; Yale Global Tic Severity Scale (YGTSS)). Six (33%) of 18
patients in the quetiapine group and six (30%) of 20 patients in the placebo group were responders.
Conclusion: The results of this study show that the augmentation of SRI
treatment in severe OCD has no additional effect. Quetiapine was generally well tolerated.
85
OTHER - Free Communications
FC-03
Other/Neurophysiology
T12 Other
FC-03-01
Hypofrontality induced by violent video game playing in
young adulthood
Yuan-Hwa Chou
Taipei Veterans General Hospit, Psychiatry, Taiwan
Tung-Ping Su, Bang-Hung Yang, Shyh-Jen Wang
Introduction: Video game is one of the most popular amusements in
modern life, which involves various stimuli and requires various cognitive
functions. The purpose of this study was to determine the effect of violent video game playing on cerebral blood flow (CBF) in young adulthood.
Method: Twelve healthy subjects (averaged age 223.2 years) were
recruited. Each subject had the first single photon emission computed
tomography with 99mTc ECD measurement as baseline and the second
after 30 min violent video game playing immediately. Statistic Parametric
Mapping (SPM2) was used for image analysis
Results: The results showed that CBF was significantly decreased in left
frontal cortex including frontal eye field (Brodmann 8, Z-score 4.28), dorsolateral prefrontal cortex (Brodmann 9, 46, Z-score 4.60, 4.66) and inferior prefrontal gyrus (Brodmann areas 47, Z-score 3.83), whereas CBF was
increased in right temporal cortex, angular gyrus part of Wernickes area
(Brodmann area 39, Z-score 4.04) and right occipital cortex, including
visual association cortex (Brodmann 18, 19, Z-score 3.54, 3.55) and
fusiform gyrus (Brodmann areas 37, z-score 3.89).
Conclusion: To our knowledge this is the first study demonstrated
hypofrontality induced by violent video game playing in young adulthood.
This finding is similar to previous studies which showed hypofrontality in
patient with major depression or schizophrenia. We suggest that clinical
study regarding relationship of violent video game playing and mental disorders has to be conducted in adolescence or young adulthood urgently.
References: 1. Molina V, Sanz J, Reig S, Martinez R, Sarramea F, Luque
R, Benito C, Gispert JD, Pascau J, Desco M: Hypofrontality in men with
first-episode psychosis. British Journal of Psychiatry 2005; 186:203-8 2.
Galynker, II, Cai J, Ongseng F, Finestone H, Dutta E, Serseni D:
Hypofrontality and negative symptoms in major depressive disorder.
Journal of Nuclear Medicine 1998; 39(4):608-12
FC-03-02
P300 event-related potentials in euthymic bipolar patients
Lahera Guillermo
Principe de Asturias Hospital, Psychiatry, Madrid, Spain
Guillermo Lahera, Antonio Pedrera, Lidia Cabanes, Jose Manuel Montes,
Jeronimo Saiz-Ruiz, Patricia Simal, Adolfo Benito
Introduction: Fewer reports have documented P300 responses in
euthymic bipolar patients. These studies report increased latency and,
sometimes, decreased amplitude, but one confounding variable was the
active mood symptoms.
Method: Objective: To asses P300 latency and amplitude in bipolar
patients without active mood symptoms. Method: The auditory P300
event-related potential (ERP) and performance on Asarnov Sustained Test
and Wisconsin Sort Card Test were evaluated in 24 subjects meeting
DSM-IV criteria for Bipolar Disorder type I. They were described as
euthymic by their consultants, but Hamilton Rating Scale and Young
Mania Rating Scale were used in order to confirm it (<8; <8).
Results: Mean P300 latency was 335, 95 ms (SD 37, 17) and mean amplitude was 10, 13 microV (SD 4,04). There were no significant differences
between these findings and the P300 responses of an equivalent sample
of healthy volunteers (latency 331, 27/SD 23, 12; amplitude 11, 05/SD 5, 31).
Only three patients had a deviation of 2SD from these reference data.
Performance in sustained attention and executive function had no significant influence in the P300 responses (Pearson, p: n.s.)
Conclusion: Abnormalities in P300 event-related potentials in Bipolar
Disorder could be related to subsyndromic mood disorder, and they disappear with restricted criteria of euthymia.
86
References: 1. ODonnell BF, Vohs JL, Hetrick WP, Carroll CA, Shekhar A.
Auditory event-related potential abnormalities in bipolar disorder and
schizophrenia. Int J Psychophysiol. 2004 Jun;53(1):45-55 2.Souza VB,
Muir WJ, Walker MT, Glabus MF, Roxborough HM, Sharp CW, Dunan JR,
Blackwood DH. Auditory P300 event-related potentials and neuropsychological performance in schizophrenia and bipolar affective disorder. Biol
Psychiatry. 1995 Mar 1;37(5):300-10
FC-03-03
Electrophysiological evidence in support of substance P as
an endogenous psychogenic peptide
Samuel Kombian
Faculty of Pharmacy, Applied Therapeutics, Kuwait City, Kuwait
Introduction: Behavioral, neurochemical and pharmacological evidence
indicate that substance P (SP)acts like cocaine or amphetamine. However,
the cellular mechanism(s) by which substance P produces these cocainelike effects are not well known. We hypothesize that SP modifies synaptic
transmission in the nucleus accumbens (NAc) to produce these effects.
Methods: Using in vitro electrophysiological patch clamp recordings in
the NAc of the rat, we examined the effects of SP on excitatory and inhibitory synaptic transmission in the NAc to test this hypothesis.
Results: Bath application of SP caused a concentration-dependent decrease in evoked excitatory postsynaptic currents (EPSCs) and inhibitory
postsynaptic currents (IPSCs).These effects were only partially reversible
upon washout. The depression caused by 1 uM SP was about 42% and
25% on EPSC and IPSC respectively.This SP-induced EPSC and IPCS
depression could be mimicked by a neurokinin 1(NK1) receptor agonist,
[Sar9,Met(O2)]-SP and blocked by pretreatment with an NK1 receptor
antagonist LY732 138. The SP-induced depression of EPSCs/IPSCs could
also be blocked with dopamine D1-like receptor antagonist SCH23390
but not sulpriride, the D2 antagonist. It could also be blocked by enhancing intracellular cyclic AMP levels but not affected by blocking protein
kinase A (PKA). By contrast to PKA, activators of protein kinase C mimicked the effect of SP while inhibitors of PKC blocked them.
Conclusion: The above effects of SP on EPSC and IPSC in the NAc and
their pharmacological profile are similar to those reported for cocaine and
amphetamine in this nucleus.SP may therefore serve as an endogenous
psychogenic substance that mediates the rewarding effects that animals
derive from substances or activities without the use of exogenous psychogenic substances such as cocaine or amphetamine.
References: Kombian et al, 2003, J. Neurophysiology 89, 728-737.
Loonam et al., 2003, Life Sci. 73(6) 727-739. Kombian et al.,2003, Eur. J.
Neurosci., 18, 1-9. Matowe et al., 2006 MPP(In press).
FC-03-04
Ayurveda (Indian traditional system of medicine) therapies
modulate cardiac autonomic balance in major depressiona clinical study with heart rate variability measures
Kishore Kumar Ramakrishna
NIMHANS, Neurophysiology, Bangalore, India
Kaviraja Udupa, Jagadisha Thirthalli, B. N. Gangadhar, G. S. Lavekar,
T. R. Raju, T. N. Sathyaprabha
Introduction: Ayurveda is emerging as among the most effective treatments for depression. The descriptions of depression in ayurveda implicate the involvement of the heart. Cardiac autonomic involvement in
depression has been suggested in recent times. Clinical improvement produced by ayurvedic antidepressant therapy could improve the autonomic
balance too. Hence we planned a study to investigate the effect of
ayurvedic antidepressant management on autonomic functions measured
by heart rate variability (HRV) in depression patients and correlate with
clinical improvement.
Method: 26 drug naive patients (age:28.27 9.53; 13 males) suffering
from Major depression (Satisfying DSM IV-TR criteria) were recruited.
Their HRV as well as Hamilton depression-rating scales (HDRS) were measured before and one month after Ayurvedic antidepressant treatment,
which consisted of oral administration of poly-herbal formulation known
as Ayushman-15 and panchakarma therapy.
Results: The patients showed a significant clinical improvement as

assessed by HDRS after one month of ayurvedic therapy. There was a
reduction of HDRS scores from 22.69 3.84 to 11.00 4.68. There was
a significant modulation of HRV parameters. The HFnu (indicator of
parasympathetic activity) significantly increased from 36.45 11.98 to
46.41 11.03, LF nu (indicator of sympathetic& parasympathetic activity)
significantly decreased from 55.20 13.61 to 42.77 11.63 and LF/HF
ratio (indicator of sympathovagal balance) significantly decreased from
1.78 1.01 to 1.05 0.66, following ayurvedic therapy. There was positive correlation between the changes in HRV parameters and clinical
improvement.
Conclusion: Ayushman-15 and panchakarma therapy comprise effective
Ayurvedic antidepressant management. The treatment modulates the
cardiac autonomic tone towards increasing the parasympathetic activity
(as shown by increase of HFnu) and decreasing the sympathetic activity
(as shown by decrease in LFnu) & and restoring the sympathovagal balance.
Placebo-controlled studies with biochemical investigation would throw
more light into the mechanism of such modulation.
References: Acknowledgement : This project was funded by Central
Council for research in Aryurveda and Siddha (CCRAS), INDIA
FC-08
Other
T12 Other
FC-08-01
Orexin A and total ghrelin plasma levels in patients with
restrictive type of anorexia nervosa
Malgorzata Janas-Kozik
Dept. of Clinic of Psychiatry, and Psychotherapy, Poland
Irena Krupka-Matuszcyk, Malgorzata Stachowicz
Introduction: The aim of the study was the analysis of the orexinA and
total ghrelin plasma levels in girls with restrictive type of anorexia nervosa
during cognitive-behavioural treatment.
Method: A group of 30 girls with AN-R was studied before and after
3 and 6 months of treatment. The group of 20 healthy girls served as a
control group. All samples of orexin A and total ghrelin plasma levels
were determined by radioimmunoassay (RIA, Linco Research, Inc.) using
LKB Wallac Clini Gamma 1272 gamma counter. The procedure was
according to the producent instruction. Statistical analysis of significance
was carried out by the t-Student test, the non-paired t-Student test and
U Mann-Whitney test and Spearmans correlation.
Results: During 6 months observation BMI in AN-R girls was increased
but it was lower than BMI in control group in all time. The mean orexin A
plasma levels in AN-R girls were 42.1 pg/ml before treatment, 11.4 pg/ml
after 3 month of treatment and 9.8 pg/ml after 6 month of treatment.
Plasma concentration of orexinA in AN-R patients during 6 months observation is decreased. In the control group the mean orexinA plasma level
was 77.4 pg/ml. During therapy the mean orexinA plasma levels were significantly lower than those observed in the control group (p<0,001,
p<0,001 respectively-U Mann-Whitney test). Initial mean plasma ghrelin
levels in AN girls (6652,1 pg/ml) were significantly higher (p<0.001;
paired test) than after the three and six months of treatment
(3858,5 pg/ml; 3187,4 pg/ml). The mean ghrelin levels in AN girls during
therapy were significantly lower than those observed in the control group
(4855,8 pg/ml; p<0,01, p<0,001 respectively).
Conclusion: In the course of AN-R, the orexinA concentration in plasma
remains on a low level regardless of BMI, which may prove to be one of
the biological susceptibility markers of AN and the total ghrelin plasma
level is a result of changing pathological feeding behaviour.
FC-08-02
Is the subtyping of panic attacks valid?
Vladan Starcevic
University of Sydney, Nepean Hospital, Psych. Med., Penrith NSW,
Australia
Introduction: In the DSM system, recurrent unexpected panic attacks are
a crucial feature of panic disorder, whereas situationally predisposed and
situationally bound panic attacks often characterise agoraphobia, social
anxiety disorder and specific phobia. The aim of this presentation is to
examine the validity of the subtyping of panic attacks into unexpected
(spontaneous) and situational.
Method: A comprehensive literature review.
Results: Research findings are contradictory. Some studies (e.g.,
Uhlenhuth et al, 2006) suggest that the psychopathology of the unexpected and situational panic attacks differs significantly; the former have
a biological core and tend to respond to pharmacological treatment,
whereas the latter have a more prominent psychological or cognitive
component and may respond better to psychological treatment.
However, other recent research (Kessler et al, 2006) found that many
attacks initially believed to be unexpected, were subsequently classified as
situational, and that most panic attacks were to some extent situational,
even among people with panic disorder. These findings: 1) raise doubt
about a reliable distinction between the unexpected and situational panic
attacks, and 2) call into question the proposition that the unexpected
panic attacks are unique to panic disorder.
Conclusion: 1) The distinction between the unexpected and situational
panic attacks may have face validity to the extent that sufferers believe
that their attacks come out of nowhere or that they are triggered by
something. 2) The subtyping of panic attacks does not have sufficient
descriptive validity because the unexpected panic attacks may not be specific for panic disorder, and situational attacks are not exclusive to phobic
and other anxiety disorders. Also, boundaries between the unexpected
and situational panic attacks are unclear and arbitrary. 3) The main problem with the subtyping of panic attacks arises from interpretation of the
context in which they occur: while panic attacks may seem to occur
from clear blue skies to some clinicians, to others these same attacks
appear to be triggered by certain situational factors. 4) There is no sufficient evidence that the unexpected and situational panic attacks have a
distinct course, prognosis and treatment response. Therefore, the subtyping of panic attacks does not have a solid predictive validity.
References: Kessler RC, Chiu WT, Jin R, et al (2006) The epidemiology of
panic attacks, panic disorder, and agoraphobia in the National
Comorbidity Survey Replication. Arch Gen Psychiatry, 63, 415-424.
Uhlenhuth EH, Leon AC, Matuzas W (2006) Psychopathology of panic
attacks in panic disorder. J Affect Disord, 92, 55-62.
FC-08-03
Mental health - psychoeducation and clinical social work
techniques in a day clinic in rural lower Austria /Europe - a
modell towards best practise
Margit Margareta Holzer
Tagesklinik Neunkirchen, Sozialpsychiatrische Abteilung, Mdling,
Austria
Christian Simhandl, Barbara Koenig
Introduction: We so often talk about all kinds of mental illnesses, we
classify them, but we do not often talk about Mental Health and how we
can achieve/improve it. This fact has to be brought to the doorsteps of
researchers, health practitioners, educationist, social scientists and students. Our oral presentation is going to be a compendium of information
towards a modell of Best Practise.
Method: A brief introduction to the essentials of Psychoeducation and
Social Work in clinical settings in a rural dayclinic is followed by the presentation of specific methods and techniques to motivate our
clients/patient and improve their ability to participate, interact and cooperate with our multicisciplinary team towards their own well-being.
Results: Through our multicisciplinary approach and stimulation patients
often leave the dayclinic very concious and enlightened about their specific situation and learn how to live with it in a positive way.
87
Conclusion: Our specific experience has shown that our patient/clients

have a big potential within themselves and if we assist them with the
right ethical approach and attitude we can achieve very positive results
towards improving their wel-being and integration in society.
References: Information on the psychometric properties of techniques
highlight the process of our evalution and interpration done by our clinical psycologist
FC-08-04
Sports for psychiatric patients at a community mental
health center
Eleonore Miller-Reiter
Psychosoziale Dienste, SPA Floridsdorf, Wien, Austria
S. Ebner, D. Kfihmayer, G. Smekal, R. Pokan
Introduction: Meeting the needs and interests of patients in an outpatient clinic with longterm care duties is always a challenge. According to
the diversity of the clientel (age, background, diagnosis,etc) we are trying
to offer new perspectives to our often socially deprived patients aside of
the state of the art medical standard. Physical activity can be prophylactic
against the development of multiple problems common in severly psychiatrically ill patients. There is also some evidence that it can help against
depressive symptoms and have positive effects on behaviour in chronic
schizophrenic patients(1,2). Therefore we decided to offer a 3 months
long sports programme for our patiens which was very well accepted.
Before and after the trainingperiode participants performed an incremental exercise test (cycle ergometer) measuring heart rate (HR) and respiratory gas exchange measures to determine HRmax and VO2max as well as
HR and VO2 at the respiratory compensation point (RCP). To evaluate the
health-related quality of life we used the SF-36 self-administered questionnaire. Sportphysiological data, lifestyle benefits and impressions
about the classes will be presented in the talk.
References: (1)Brosse AL, Sheets ES, Lett HS, Blumenthal JA. Exercise and
the treatment of clinical depression in adults: recent findings and furture
directions. Sports Med 2002: 32: 741-760. Chamovw AS. Positive shortterm effects of acticity on behviour in chronic schizophrenic patients. Br J
Clin Psychol. 1986 May; 25 (PT2): 125-33
FC-16
Other II
T12 Other
FC-16-01
Characteristics associated with the prevalence of mental
disorders in the Malaysian population- the MMHS study
Saroja Krishnaswamy
Kavitha Subramaniam, Tishya Indran, Abdul Aziz Jemain, Abdul Hamid
Introduction: Mental disorders are a growing health concern in the
world that affects both the developed nations and third world countries.
These problems have also been associated with high rates of disability in
various reports. In Malaysia, despite being recognised as a growing health
threat, there arent precise information on severity of this problem.
Objective:The Malaysian Mental Health Survey (MMHS) aims to determine
the prevalence of mental disorders in Malaysia and its association with
risk factors and quality of life.
Method: Multistage cluster sampling method was used to obtain samples, with racial proportion as main sampling criteria. Required sample
size was calculated using the epi-info software based on the disorders
with lowest prevalence rate, panic disorder ( Singleton et al., 2002).The
estimated sample size was 3500 at 80% confidence level for the whole
country. Trained enumerators carried out the interview, with the aid of
questionnaires such as CIS-R, Psychisis Screening Questionnaire, AUDIT
and so on. SCAN was administered to any respondents who had at least
one of the psychotic symptoms by trained psychiatrists.
88
Results: Our findings show that an overall prevalence rate mental illness
in the Malaysian population is 6%. A few factors were found to be associated with the presence of mental illness in the Malaysian population.
The socio demographic factors were female gender, non-Chinese ethnicity,
aged blow 29 years old, being divorced Socio economic factors associated
were not having own transport and presence of difficulties at work.
Hereditary factor, or presence of family history of mental illness was associated with the presence if mental illness. Social capital factors and a few
life events such as marital separation, serious financial constrains etc in
past one year period prior to the survey were also found to be associated
with the prevalence of mental illness.
Conclusion: Prevalence rate of mental illness was 6% in the Malaysian
population. A few factors were found to be significantly associated with
the prevalence of mental illnesses. The findings would be discussed in
detail. CIS-R = Clinical Interview Schedule- Revised AUDIT- Alcohol Usage
Disorder Identification Test
FC-16-02
Analysis of relation between time management behaviors
and occupational stress of medical surgical ward's head
nurses of educational hospitals depend on Shaheed
Beheshti Medical University
Haydeh Hahshemizadeh
Azad Islamic Univ., of Ghoochan Iran, Nursing, Mashhad, Iran
Introduction: According to lakein description of time management, individuals first determine their needs and want and then rank them of
importance. Specific activities include setting goals to achieve the needs
or wants and prioritizing the tasks necessary to accomplish them. The
tasks of at most importance are then matched to the time and resources
available by planning, scheduling, and making lists.analysis of relation
between time management behaviors (setting goal and priorities, mechanics of time management , control of time and organization ) and occupational stress (role overload , role ambiguity and role conflict )
Methods: 30 nurses (all of the samples) participate in this research. A
questionnaire which had 57 questions was used. For data analysis, X2 and
Pearson correlation coefficient were used.
Results: In general most of sample located in good level of T.M.B (63.4
%). In addition most of sample (50%) experience occupational stress in
the normal level. Finally Meaningful relation is seen between T.M.B and
occupational stress (r = - 0.81 P< 0.001).
Conclusion: It is important to distinguish among the different facets of
time management .The low correlation among the factors indicate that,
for instance , if a person sets goal it does not necessarily follow that he
or she feels in control of time or makes lists. Finally time management
behaviors can reduce occupational stress.
FC-16-03
Neurobiological aspects of CBT with anxiety disorders
Jan Prasko
Republic
Jiri Horacek, Beata Paskova
Noradrenergic pathway have been associated with fear and arousal and
play an important role in the bodys response to threat (Nutt et al. 1999).
The most investigators believe, that an increase of serotonin transmission
decreased anxiety disorders. The evidence for this is that the SSRIs are
effective in anxiety disorders. The serotonergic innervations of the amygdale and the hippocampus by the dorsal raphe is believed to mediate anxiogenic effects via 5-HT2A receptors. In contrast, the median raphe innervations of hippocampal 5-HT1A receptors has been hypothesised to facilitate the disconnection of previously learned associations with aversive
events or to suppress formation of new associations, thus providing a
resilience to aversive events (Graeff 1993). LeDoux (1998) have demonstrated the central role played by the amygdale in the mediation of fear
reactions. The bed nucleus of the stria terminalis, may be involved in anxiety (Davis 1998). Thalamo-amygdale pathways that bypass the cerebral
cortex may trigger conditioned responses before the stimulus reaches full
awareness, providing an explanation for unconscious conditioned phobic

responses to fear-relevant stimuli. Fear conditioning has been used as a
model for the occurrence of pathological anxiety responses to seemingly
neutral stimuli. The neutral stimulus was originally paired with truly
fearful stimulus, which now may be forgotten. Patients then begin to
avoid these stimuli in their everyday life. Anxiety has both subcortical and
cortical components. Various psychotherapies target the cortical components and the memory systems of the hippocampus. Behavioural therapies (systematic desensitization, exposure) produce deconditioning.
This process occurs by retraining hippocampal neurons to reorganize the
contextual cues that they store, so that they are no longer associated with
danger signal . Cognitive therapy or other speaking psychotherapies, in
which the contextual memories are explored, may attack the same problem from the cortical level. Supported by the project 1M0517 MZCR.
FC-16-04
The neuronal correlate of mentalization: An unitary model
Jacques Van Hoof
GGZ- Oost-Brabant, Psychiatry, Beuningen, Netherlands
Introduction: It remains a mystery as to how genetic and environmental
factors cause symptoms relevant for psychotherapy. The objective is to
develop a pathophysiological model that has greater explanatory power
than existing hypotheses.
Methods: Published findings are integrated with recent data from
human and animal studies of striatal and cerebellar functions.
Results: The analysis shows that during brain development two primarily
motor-control mechanisms (drive and guidance) organized through a ventral, respectively, a dorsal cortical-subcortical circuitry are applied in a
repetitive way at the limbic level relevant for the organisation of intentions. This repetitive application allow the creation of unique human capacities; viz. the ability to create (meta) representations, language and consciousness, but also an increased capacity to deal with conflicting demands
and emotions. In the model it is assumed that this development is the
neuronal correlate for the process called mentalization. Evidence is accumulating that the principally genetically based reliance on one or both
types of mechanisms has a bimodal distribution. A genetically based
insufficient development of one of both mechanisms and an exaggerated
reliance on the other mechanism cause an imbalance. The repetitive
implementation of these mechanisms will increase this imbalance and
create a situation where comparatively small stressors produce a tipping
of the scale manifesting itself as developmental problems relevant for
psychotherapy.
Conclusion: This model has a greater explanatory power than current
alternatives and therefore it will provide a useful framework for further
research.
References: Van Hoof J.J.M. (2003a) The Abnormal Development of
Drive and Guidance Mechanisms in the Brain: The Pathogenesis of
Schizophrenia. Acta Neuropsychiatrica 14, 134-146Van Hoof
J.J.M.(2003b) A motor hypothesis of the origin of schizophrenia.
Schizophrenia Research 62(2003) 183-185Van Hoof J.J.M. (2004) Van
regressie naar progressie: een nieuw analytisch ontwikkelingsmodel. In
Jonker Pool G et al (eds) Handboek voor psychologische interventies bij
chronisch-somatische aandoeningen. Van Gorcum & Comp Assen. Hfd
15, 164-177
FC-19
Other/Suicide
T12 Other
FC-19-01
Sexual violence in childhood: Neurobiologics and clinics
consequences
Jose Lippi
School of Medicine, Psychiatry, Belo Horizonte, Brazil
Method: Based on chronological research in specialized literature, on the

study of its psychiatric consequences and the clinical experience of the
author; through Longitudinal-observational-retrospective study conceived to establish the etiological relationship between disorder of low
incidence, and/or conditions of extended latency.
Results: Sexual violence experienced in infancy may provoke neurobiological and clinical consequences, with some emerging late in life. Several
regions in the brain suffer structural and functional changes, in all likelihood triggered by abuse and neglect suffered in childhood. The most
affected regions are: the limbic system: the corpus callosum, prefrontal
cortex and gyrus cinguli. Posttraumatic stress disorder, borderline
Personality disorder (BPD), depression (D) and attempted suicide (SA), at
any age, are associated with sexual violence suffered in childhood.
Conclusion: Sexual abuse in childhood is likely to play a part and be the
precursor of changes in the Limbic system: hippocampus; amygdala; corpus callosum; gyrus cinguli and prefrontal cortex and the precursor too
of serious psychiatric illnesses: Posttraumatic Stress Disorder (PTSD);
Borderline Personality Disorder (BPD); Depression (D) and Suicide
Attempted (SA).
FC-19-02
Are there differences in platelet serotonin and serum cholesterol levels in suicidal and non-suicidal male patients
with first psychotic episode?
Darko Marcinko
Marko Martinac, Miro Jakovljevi, Marija Sari, Bjanka Vuksan, Alma
Mihaljevi-Peles, Nela Pivac, Dorotea Muck-Seler
Introduction: Suicidal behavior is a major health risk in psychiatric disorders,
especially in schizophrenia, and up to 10% patients will commit suicide. The
neurobiology of suicide is still unclear. Suicidality has been related to a
decreased central serotonergic (5-hydroxytryptamine, 5-HT) function and
reduced cholesterol levels. Platelet 5-HT was used as a peripheral marker of
the central serotonergic synaptosomes.
Method: The hypothesis was that suicidal patients in the first episode of
psychosis will have different serum cholesterol and platelet 5-HT concentrations than non-suicidal patients in the first episode of psychosis. The
aim of this study was to evaluate serum cholesterol and platelet 5-HT concentrations in suicidal and non-suicidal men in the first episode of psychosis and in healthy male controls. Venous blood samples were collected
within 24 hours of admission, and serum cholesterol and platelet 5-HT
were determined enzymatically and fluorimetrically.
Results: Platelet 5-HT and serum cholesterol concentrations were significantly lower in suicidal than in non-suicidal patients in the first episode of
psychosis, and than in healthy controls.
Conclusion: Our results suggest that lower concentrations of serum cholesterol and platelet 5-HT in patients with the first episode of psychosis
might be useful biological markers of suicidality.
References: Marcinko, D., Martinac, M., Karlovic, D., Loncar, C., 2004.
Cholesterol serum levels in violent and non-violent young male schizophrenic suicide attempters. Psychiatria Danubina 16, 161-164.
Marcinko, D., Martinac, M., Karlovic, D., Filipcic, I., Loncar, C., Pivac, N.,
Jakovljevic, M., 2005. Are there differences in serum cholesterol and cortisol concentrations between violent and non-violent schizophrenic male
suicide attempters? Collegium Antropologicum 29, 153-157.
Muck-Seler, D., Jakovljevic, M., Pivac, N., 1996. Platelet 5-HT concentrations and suicidal behavior in recurrent major depression. Journal of
Affective Disorders 39, 73-80. Pivac, N., Jakovljevic, M., Muck-Seler, D.,
Brzovic, Z., 1997. Hypothalamic-pituitary-adrenal axis function and
platelet serotonin concentrations in depressed patients. Psychiatry
Research 73, 123-132. Pivac, N., Muck-Seler, D., Barisicic, I., Jakovljevic,
M., Puretic, Z., 2001. Platelet serotonin concentration in dialysis patients
with somatic symptoms of depression. Life Science 68, 2423-2433.
Stahl, S.M., 1985. Platelets as pharmacological models for the receptors
and biochemistry of monoaminergic neurons. In: Longenecker (Ed.), The
Platelets: Physiology and Pharmacology, pp. 307-340.
Introduction: To establish evidence that Childhood sexual abuse may

cause structural and functional changes in the brain and the installation
of psychiatric disorders.
89
FC-19-03
Suicidal behaviour of patients in urgent psychiatry outpatients department and psychosocial characteristics of
suicide victims in central slovenian region
Peter Pregelj
Un.Psychiatric Hosp.Ljubljana, KOKP, Slovenia
Martina Tomori, Marga Kocmur
Introduction: Slovenia has one of the highest suicide rates in Europe
(overall 29 per 100000). The aim of the study was to investigate the differences in expressed suicidal behaviour regarding diagnoses and prescribed medications at arrival in Urgent Psychiatry Outpatients
Department (UPOD) at University Psychiatric Hospital Ljubljana and to
evaluate psychosocial characteristics of suicide victims in central Slovenian
region.
Method: From the case register of UPOD all admissions in year 2004 and
2005 were extracted. During this time 2707 patients were examined in
UPOD. Suicidal behaviour, prescribed psychotropic drugs and diagnoses
of the patients was evaluated. On the other hand, in the tree-year period
66 suicide victims (20 women and 46 men) in the central region of
Slovenia were examined using the method of psychological autopsy.
Results: Suicidal ideations were observed in 22% of all patients in urgent
psychiatry outpatients department and another 7% of patients were
examined after suicide attempt. The highest share of patients with prescribed psychotropic medications was observed in patients with mood
disorders (46%). However, we have not observed differences in expressed
suicidal ideations or previous suicide attempts between patients with
mood disorders receiving serotonin reuptake inhibitors (SSRI) and those
receiving other antidepressants (p>0.05). Although patients with prescribed psychotropic drugs have expressed suicidal thoughts more often
than other patients we have observed that the opposite was true for suicide attempts (p<0.001). Patients with family history of suicide expressed
suicidal behaviour more often than others. The same was true for the suicide victims with family history of suicide. We also observed that suicide
victims with family history of suicide have higher number of previous suicide attempts and express aggression against their family members more
often than victims without family history of suicide.
Conclusion: Accordingly to preliminary observations the following study
indicates that suicide victims with family history of suicide could have
more stressors in childhood and could be more prone to aggressive
behaviour than victims without family history of suicide.
References: D.J. Statham, A.C. Heath and P.A. Madden et al., Suicidal
behaviour an epidemiological and genetic study, Psychol Med 28 (1998),
pp. 839-855.
FC-23
Other III
T12 Other
FC-23-01
An unusual conversion in a patient with fibromyalgia syndrome, and treatment implications: A single case study
Samvel Margaryan
Center, Day-Department, Yerevan, Armenia
Introduction: Despite increasing recognition of the fibromyalgia syndrome
(FS) as a clinical entity, its etiology remains obscure. The lack of a definitive pathophysiology has led several investigators to examine the role of
psychological/psychiatric factors in the presentation of symptoms associated with FS. The main objective of this study is to describe an unusual
manifestation of somatoform conversion in a patient with FS and show
the effectiveness of combination of antidepressants in its treatment.
Method: A 46-year old woman with primary fibromyalgia, referred to a
center of mental health by rheumatologist after an ineffective treatment.
In a single case study a 1-year course of outpatient observation and treatment was provided for a patient who had FS. She was investigated by
dynamic clinical-psychopathological method. Mood improvement was
90
evaluated using the 21-item Hamilton Rating Scale for Depression. She
also completed Hopkins Symptom Inventory (SCL-90).
Results: The patient had a previous history of a major depressive episode
8 years ago, but after a month of inpatient treatment recovered and
never applied to a physician later than. Her state now characterized by
generalized aches, pains, tender points, stiffness, fatigue, depression, and
insomnia. There were manifested fits - after stress or without it - with
swelling and enlargement of different parts of body - mainly abdomen
and proximal parts of limbs. She became immobile about 2-3 hours, and
then expressed fatigue and pains characterize the state for 2-3 days. The
treatment with antidepressants in turn (singly) - amitriptyline, imipramine,
and fluoxetine - was ineffective during 4 months. A considerable
improvement of fibromyalgia symptoms and pain severity was recorded
two weeks after the prescription of tianeptine (37,5 mg/daily) and maprotiline (25 mg for the night) - the fits became very rare. She did well on the
Hamilton Scale for Depression and SCL-90 (significant improvement on
the scales of somatisation and depression). There was still insomnia. The
relapses were seen only as a result of stressful events or decrease of the
dosages of antidepressants.
Conclusion: Psychiatric co morbidities are very important in the treatment of patient with FS. The combination of antidepressants could be
effective in the treatment of FS and co morbid conversions. However, it
is impossible to generalize from a single case study, this work could be
considered as a pilot study and further work is recommended.
FC-23-02
Serum immunoglobulin profiles in patients with somatization disorder
Shalahuddin Qusar
BSMM University, Dept. of Psychiatry, Dhaka, Bangladesh
Iqbal Hossain, Nazrul Islam, Nahid Mahjabin Morshed, Abdul Hasna
Introduction: Somatization disorder is one of the most common psychiatric illnesses that represent a group of disorders characterized by physical symptoms. Early detection makes life more comfortable to the patient
of somatization disorder. Immunoglobulin profiles may be used as biological marker for early detection of somatization disorder.
Method: The study was conducted among 46 somatization disorder
patients who were newly diagnosed clinically by using DSM-1V by psychiatrist and 45 healthy controls were taken matched with age and sex.
Study populations were selected from Bangabandhu Shiekh Mujib
Medical University by random sampling. Blood samples (5ml venous
blood taken from each study population) were taken by aseptic condition.
The blood sample was allowed to clot at room temperature for 60 minutes, and then centrifuged at 3000 rpm for 15 minutes to collect the
serum. The serum was aliquot in eppendorf tubes and stored at -80c
until analysis of immunoglobulins. Serum immunoglobulin concentrations
were determined by turbidimetry method using immunoglobulin kit.
Results: The serum concentrations of IgG, IgM and IgA of patients with
somatization disorder were 24.144.44 (g/L), 2.051.12 (g/L) and
2.110.75 (g/L), while these were 26.344.94 (g/L), 2.361.25 (g/L) and
2.760.86 (g/L) in control subjects respectively. The concentration of IgA
decreased significantly (P=0.02) in somatization disorder patients while
the concentration of IgG (P=0.218) and IgM (P=0.443) were found to be
unchanged. Mean Body Mass Index (BMI) of the patients (20.26
3.04 kg/m2) was significantly (p<0.001) lower than that of the control
subjects (23.562.03 kg/m2). Correlative analysis suggested that only the
IgA value had a significant inverse correlation with the BMI (r = -0.553,
p = 0.006), which was further justified from the regression analysis (R2 =
43%; t = 3.948; p = 0.001) and one-way ANOVA test (F = 9.245; p =
0.006).
Conclusion: IgA level was found to be decreased significantly in patients
of somatization disorder that may have a prognostic significance for the
detection of somatization disorder and may be thought as biological
marker. But further study is needed to support these findings though it
throws some light regarding this aspect.
FC-23-03
Residual AD/HD in adults
Jan Wollenberg
Sykehuset-Innlandet, DPS Gjoevik, poliklinikk Toten, Lena, Norway
Introduction: The present study presents the results of a project in
Norway to get a reduction of time from referral to diagnosis of Residual
AD/HD or not at the adult mental health outpatient teams in Gjoevik and
Toten . In the study the DSM-IV diagnosis 314.00 - ADHD Predominantly
Inattentive Type has been included. Otherwise we used The Tenth Revision
of the International Classification of Diseases ( ICD-10) diagnosis: F90.0
Disturbance of activity and attention.
Method: A breakthrough series and statistical processcontrol were used
for the goal. We worked out an internal procedure for the community
mental health teams and an information booklet for patients. In addition,
information about the breakthrough series have been made available to
all staff members of the teams. Also copies were made of the unravelling
material based on material from the expert team at Ullevaal University
Hospital in Oslo. The final diagnosis was made by a specialist of psychiatry, and the diagnosis was quality secured at the expert team.
Results: The base data were 12 cases (7 from Toten) diagnosed Residual
AD/HD from 1.1.2003 to 18.04.2004. The unravelling time was 124 days.
The project data were 23 cases (20 cases from Toten) from which 17 of
the cases got the diagnosis Residual AD/HD. Unravelling time was 105
days.The reduction of time from referral to diagnosis was reduced by
15% (p<0.01). But at Toten there was a clinical improvement in the number of unravelling cases in the project period of 724.04%.
Conclusion: This improvement of 724.04% is interpreted in the way, that
information to the staff meant that there was focus on Residual AD/HD
showing, that there is a big potential to improve the diagnosing of
Residual AD/HD. The diagnosis Residual AD/HD ought to be put in ICD-11.
One of more reasons is, that adult patients with the diagnosis of AD/HD
cannot get e.g. insurance against loss of ability to work because of the
stigma of the diagnosis of AD/HD, while a diagnosis of Residual AD/HD is
a milder condition. If treated, the prognosis is good. The prevalence is
estimated to be 2-4.4%.
References: www.socialstyrelsen.se: ADHD in children and adults. Nils
Olav Aanonsen (red.): ADHD Diagnosis, clinic and treatment in adults.
www.shdir.no: Guide in diagnosing and treatment of AD/HD (IS-1244).
Results: Clinical investigation of the metabolic syndrome in patients with

mental disorders, except schizophrenia, has been surprisingly scarce.
Metabolic syndrome was reported in 37-63% of the schizophrenic
patients, in 42.4% of the patients with schizo-affective disorder, in 30%
of the bipolar patients, in 36% of the patients with major depression, in
25-31.9% of the patients with combat posttraumatic stress disorder. The
prevalence of metabolic syndrome in psychiatric patients is significantly
higher compared to general population
Conclusion: Metabolic syndrome can contribute to significant morbidity
and premature mortality and should be accounted for in the treatment of
mental disorders.
FC-23-04
Mental disorders and metabolic syndrome:
A critical review
Miro Jakovljevic
Univ Hospital Zagreb, Psychiatry, Croatia
Marija Saric, Radmila Topic, Darko Marcinko
Introduction: There has been a growing interest in the effect that
comorbid mental and somatic disorders may have on each other.
Metabolic syndrome is an important risk factor for the development of
diabetes mellitus, cardiovascular disease and premature mortality.
Objectives: To examine association between various mental disorders
(schizophrenia, schizoaffective disorder, bipolar disorder, depression, posttraumatic stress disorder and other mental disorders) and metabolic syndrome and discuss the possible pathophysiologic mechanisms that may
link specific mental disorders and metabolic syndrome.
Method: A MEDLINE search, citing articles from 1966 onward, supplemented by a review of bibliographies, was conducted to identify relevant
studies. Criteria used to identify studies included (1) English language, (2)
published studies with original data in peer-reviewed journals.
91
ADDICTIVE DISORDERS - Poster
Poster
P-01
Addictive Disorders
P-01-01
Alcohol in Malaysia: Consumption pattern, related problems, and characters associated with the alcohol related
problems
Saroja Krishnaswamy
Kavitha Subramaniam, Abdul Aziz Jemain, Tishya Indran, Abdul Hamid
Introduction: Alcohol abuse has not been given much importance in
comparison to tobacco or drug abuse in Malaysia. As a result there is a
limitation in information available on this issue. Alongside with the modernization of the society it is however emerging as a social problem in the
country and therefore stands a necessity to be studied extensively.
Objective:This study has three main objectives; first to identify the pattern
of alcohol consumption in the Malaysian population if there is any.
Second is to estimate the prevalence of alcohol related problems in the
population and third to identify the high-risk group for alcohol related
problems.
Method: This is a sub study from the Malaysian Mental Health Survey
(MMHS). The participants of the MMHS were assessed for alcohol abuse
using the Alcohol Usage and Disorder Identification Test (AUDIT) instrument upon consent. Only the participants who answered the AUDIT questionnaire were included in this study.
Results: 74% of the MMHS participants (N=2709) participated in the
study. A number of 957 subjects were did not respond the questionnaire.
13% of the non-response was due to sensitivity to and the rest 87% was
due to the request by the participants to terminate the study before the
AUDIT section. The findings showed that 9% (n=237) of the subjects
were drinkers. Rate of drinkers was high among the aborigines of
Sarawak (25%) followed by Chinese (16%), Indians (13%). 18% of the
drinkers (n = 42) had alcohol related problems. Indians had highest rate
of alcohol related problems (27%) followed by the Chinese (18%).
Characters that were found to be associated with alcohol related problems were male gender (OR= 6.925, p=0.002), Indian (OR= 10.541,
p=0.000) and Chinese (OR= 7.854, p=0.000) ethnic groups, having difficulties at work place (OR= 3.75, p=0.004) and suicidal ideations (OR=
4.872, p=0.003).
Conclusion: There is a unique pattern of alcohol consumption and prevalence of alcohol related problems in Malaysia. OR= Odds Ratio
P-01-02
Low rate of alcohol abuse among psyciatric and non-psychiatric patients in Armenia
Samvel Margaryan
Center, Day-Department, Yerevan, Armenia
Samvel Sukiasyan, Narine Manasyan, Anna Babakhanyan, Arpine
Kirakosyan, Ashkhen Pogosyan
Introduction: Although the association between alcohol and mental
health problems is complex, links are without doubt. At present it is dominating the idea among psychiatrists that people who have pre-existing
mental health problem are more likely to drink hazardously than those
without, and people who drink hazardously are more likely to develop a
mental health problem than those who do not. The objective of our study
is to find out the prevalence of alcohol abuse among inpatients of a psychiatric hospital and outpatients of a multidisciplinary diagnostic center,
which could be considered as primary health care setting.
Method: Using specially designed clinical-epidemiological questionnaire
two aspects of the mentioned patients had assessed: 1) the influence of
alcohol on the psychiatric and social state of the patients; 2) the influence
of psychiatric and social states on the alcohol abuse. There were investi-
92
gated 148 patients at the Center Stress and 122Medical Center

Diagnostica. All the patients had been Armenians (Caucasians). The
first group we conditionally named psychiatric (mainly depressive, anxiety, poststress disorders), and the second one diagnostic (mainly
somatic disorders associated with depressive, somatoform, and other
neurotic disturbances).
Results: Among psychiatric patients men were 51.3 %, and among
diagnostic patients men were only 29.5 %. According to the obtained
data the overwhelming majority of the patients in both groups denied the
interrelation of the mentioned factors: 1) only 3.38 % of psychiatric
and 1.64 % of diagnostic patients mentioned any role of alcohol misuse
or abuse in their health or social problems, and 2) only 2.03 % of psychiatric and 0.82 % of diagnostic patients misused or abused alcohol
because of their health or social states. The low rate of alcoholism is associated with high consumption of the total amount of alcohol drink per
capita in Armenia.
Conclusion: Although the psychiatric disorders are common among people
with alcohol problems, the role of alcohol in the formation of mental disorders in Armenians is not significant. The findings have implications for
etiological theory and developmental model of the mental disorders.
However this study could be considered as preliminary and further
research of a longitudinal nature is recommended.
References: Sher L., Oquendo M.A., Conason A.H.,.Brent D.A,
Grunebaum M.F., Zalsman G.,.Burke A.K., Mann J.J. Clinical features of
depressed patients with or without a family history of alcoholism // Acta
Psychiatrica Scandinavica 2005; 112(4): 266-71.
P-01-03
Apoptosis of lymphocytes in alcoholic patients
Olga Fedorenko
Mental Health Institute, Biological Laboratory, Tomsk, Russia
Nikolay Bokhan, Natalya Rakitina, Svetlana Ivanova
Introduction: Programmed cell death and its morphologic manifestation
of apoptosis is essential mechanism in adult organisms to maintain
normal cellular homeostasis and reject defective cells. Although the
occurrence of apoptosis has been known for decades, it is only recently
that ethanol has been found to trigger widespread apoptosis.
Method: 24 men 31-57 years old with alcoholism (average flow of disease
was 15 years) were examined along with 20 healthy age-matched men.
The examination of alcoholics was carried out in dynamics: at receiving
patients with severe withdrawal syndrome (SWS) (first point) and after
2 week treatment (second point). We counted number of leukocytes, percent CD95+lymphocytes and morphological changes characteristic of
apoptosis in lymphocytes and neutrophiles using fluorescent and light
microscopy.
Results: The relative content of bloodstream lymphocytes expressing
receptors of readiness to Fas-dependent apoptosis (CD95) in alcoholics
with SWS and after their treatment significantly exceeds the same index
in healthy controls (p<0,05). The absolute content of CD95 lymphocytes
in alcoholic patients before and after treatment was also higher as compared with healthy individuals. Together with the readiness to apoptosis
the calculation of lymphocytes with morphological evidence of apoptosis
was conducted. The percentage and the absolute content of lymphocytes
with morphological characteristics of nuclear fragmentation in alcoholic
patients was twice as much in comparison with the corresponding indexes
of healthy men. The percentage content of apoptotic lymphocytes in
alcoholic patients was 2,68 0,46% before treatment and 2,15 1,93%
after treatment (0,97 0,35% in controls, p<0,05). Also the index of
apoptosis realization (i.e. the portion of cells with morphological characteristics of apoptosis expressed in percentage terms, from the common
amount of cells, expressing receptors of readiness to Fas-dependent
apoptosis) was calculated. It has been found that the index of apoptosis
realization was significantly decreased in alcoholic patients after the treatment in comparison with those before treatment (13,44% and 21,03%
respectively).
Conclusion: According to the performed analysis it is possible to suppose
that alcohol increases the readiness of lymphocytes to apoptosis and
under the treatment the mechanisms controlling and limiting the processes of the programmed cell death are stimulated, hence index of apoptosis realization significantly diminishes.
P-01-04
Differential manifestation of alcohol withdrawal symptoms related to serotonergic polymorphism
Chul Na
Chung Ang University Medical C, Department of Psychiatry, Seoul,
Republic of Korea
Samwook Choi, Young Sik Lee, Doug Hyun Han
Introduction: The purpose of this study was to address a role for the
5-HT receptor subunit gene in the development of alcohol dependence.
The differential manifestation of alcohol withdrawal symptoms related to
serotonergic polymorphism in patients with alcohol dependence was also
examined.
Method: It was evaluated that the role of the 5-HT1A,, 5-HT2A, 5-HT
transporter(5-HTTLPR) polymorphism to manifest the individual differences in alcohol withdrawal symptoms by an association study of 97 male
inpatients with alcohol dependence and 76 healthy controls. The patients
alcohol withdrawal symptoms were assessed with the Clinical Institute
Withdrawal Assessment for Alcohol (CIWA-Ar).
Results: In 5-HT1A receptor, the frequency of G- allele (CC) was significantly higher in the patients with alcohol dependence than the normal
control group (x2=5.03, p=0.025). The subscale score of nausea, anxiety,
headache among CIWA-Ar scale and the total score of CIWA-Ar scale in
G+ allele (CG+GG) was significantly higher than G- allele (p=0.01,
p=0.00, p=0.01, p=0.01). In 5-HT2A receptor, the genotype frequency
was significantly different between alcoholics and control subjects
(2=23.41, p=0.00), but there was a significant deviation from HardyWeinberg equilibrium in the patients. CT genotype, allele, and CT genotype group frequencies of 5-HT2A among alcoholics and normal controls
were not different in terms of all the subscale of CIWA-Ar scale. In 5HTTLPR, the frequency of L- allele(SS) was higher in the patients with
alcohol dependence compare to the normal control group, but this was
statistically insignificant (x2=3.162, p=0.075). Visual hallucination was
more severe in L+ (SL+LL) allele than L- allele (p=0.01).
Conclusion: The results suggested that 5-HT polymorphism and allelic
types revealed the difference in severity of each withdrawal symptom in
alcohol dependent patients.
P-01-05
Early electrophysiological evaluation of central and peripheral nervous system in patients with alcoholism
Carina Diaz Martinez
Dr Agostinho Neto, General Hospital, Guantanamo, Cuba
Introduction: Alcohol has been a pleasant accompaniment of human
beings since the ancient epoch. However a lot of harmful effects are
ascribed by its excessive consumption. There is a clear relation between
alcohol intake and the frequency and severity of associated diseases. It is
widely known the neurotoxic effect of alcohol damages significantly
theactivity of Nervous System but there are few reports exploring objectively this effect at the first stages of alcoholism. Electrophysiological techniques such as Brain Auditory Evoked Potential (BAEP) and Sensory and
Motor Nerves Conduction Studies (NCS) could be very useful to reveal any
NS dysfunctions in this initial period.
Methods: 50 alcoholic patients with a recent diagnosis of alcoholism and
without clinical signs of alcohol induced central or peripheral NS lesions
were evaluated using BAEP and Sensory and Motor NCS. The responses
were obtained in both sides. Absolute and interpeak latencies, amplitude
and duration of BAEP were analyzed. In the case of NCS latency, duration, amplitude, and nerve conduction velocity were computed. Median,
ulnar, peroneal and sural nerves were explored. The results were compared to those obtained in 50 normal controls. Descriptive statistic and
ANOVA test were used in statistical analyzing.
Results: 24 cases (48%) showed a significant I-V interpeak latency prolongation with mean increase 0.73 ms. 41 % of nerves showed at least one
pathological parameter. Axonal alterations predominated. The motor and
sensitive nerves were damaged but the alterations were most remarkable
in sensitive nerves especially in median and sural nerves. Finally 19
patients (38%) were diagnosed with light sensitive and motor polyneuropathy.
Conclusion: The toxic effect of alcohol affects significantly the activity of

central sensorial pathway such as auditory via and peripheral nerves even
at the first stages of alcoholism, when clinical signs of nervous system
dysfunctions are difficult to identify.
P-01-06
Pregabalin, tiapride and lorazepam in alcohol withdrawal
syndrome: A randomized multi-centre trial
Giovanni Martinotti
Univ. Cattolica d. Sacro Cuore, Inst. Psychiatry & Psychology, Rome, Italy
Marco Di Nicola, Sara Geri, Daniela Tedeschi, Roberto Romanelli, Luigi
Janiri
Introduction: Benzodiazepines are the mainstay of treatment for mildto-moderate alcohol withdrawal in outpatient settings (Shaw GK, 1995),
but they can interact with alcohol, cause motor incoordination, or be
abused. Other pharmacological treatment have been proposed with
promising results, such as dopamine antagonist (Bender S. et al., 2006),
and antiepileptics (Polycarpou A. et al., 2005 ). The aim of this randomised, multi-centre, double blind trial is to compare lorazepam, the
selective dopamine D2/D3 receptor antagonist tiapride, and the anticonvulsant pregabalin in the treatment of alcohol withdrawal syndrome.
Relapse rate, psychiatric symptoms and craving for alcohol are the secondary endpoints. Sixty patients with a diagnosis of alcohol dependence
were recruited from the DH of Clinical Psichiatry of Catholic University
Medical School in Rome and from the outpatients unit Villa Silvia in
Senigallia. Major exclusion criteria were significant hepatic or hematologic
abnormalities, the use of medications that could interfere with withdrawal symptoms, the presence of severe comorbid psychiatric disorder such
as Schizophrenia or Wernicke-Korsakoff. Patients included were orally
treated with flexible doses of lorazepam, tiapride, and pregabalin for 2
weeks after alcohol cessation. The mean initial dose was 3 mg for
lorazepam, 300 mg for tiapride and 300 mg for pregabalin. The Clinical
Institute Withdrawal Assessment for Alcohol-Revised (CIWA-AR) was
used to evaluate alcohol withdrawal symptoms. The ObsessiveCompulsive Drinking Scale (OCDS) and the Visual Analogue Scale for
Craving (VASc) were utilized to assess craving for alcohol, the Symptom
Check List (SCL-90) to assess psychiatric symptoms. Withdrawal symptoms, craving, and psychiatric symptoms decreased from baseline to the
end of the study in both the groups (p< .001). Difference between groups
was not significant. The reduction of the SCL-90 subscore for anxiety was
significantly lower in the tiapride group. All the treatments were generally
well tolerated, with a low rate of adverse events. The results of this study
confirm the efficacy and safety of lorazepam, tiapride and pregabalin for
the treatment of alcohol withdrawal syndrome. Larger sample and a
placebo-controlled design are required.
References: Shaw GK. Detoxification: the use of benzodiazepines.
Alcohol Alcohol. 1995 Nov;30(6):765-70. Bender S, Scherbaum N, Soyka
M, Ruther E, Mann K, Gastpar M. The efficacy of the dopamine D2/D3
antagonist tiapride in maintaining abstinence: a randomized, doubleblind, placebo-controlled trial in 299 alcohol-dependent patients. Int J
Neuropsychopharmacol. 2006 Nov 1;:1-8. Polycarpou A, Papanikolaou P,
Ioannidis JP, Contopoulos-Ioannidis DG. Anticonvulsants for alcohol withdrawal. Cochrane Database Syst Rev. 2005 Jul 20;(3)
P-01-07
Chronic alcoholism and quantitative analysis of eeg in
Caucasian population
Jozef Dragasek
University Hospital FNLP, I.Dep.of Psychiatry, Kosice, Slovak Republic
Eva Palova, Milena Drimalova, Maria Martinove, Dagmar Breznoscakova,
Boris Bodnar, Peter Jankovic
Introduction: Electroencephalography has shown that the brain activity
of alcoholics and nonalcoholics differs in some characteristic ways. These
differences are consistent with an imbalance between excitation and inhibition processes in the brains of alcoholics. Because the increase in beta
power in abstinent alcoholics was not related to length of abstinence and
also is present in offspring of alcoholics at a risk for alcohol dependence,
93
these findings suggest that excess beta power is a trait rather than state
variable related to underlying genetic predisposition and not to alcohol
use or other factors.
Method: In our study, the magnitude of EEG power spectra of delta,
theta, alpha and beta power was examined to address the relationship
between EEG spectral changes and alcohol dependence. A group of
54 male chronic alcoholics were selected according to inclusion and exclusion criteria. We compared this group with 54 age- and gender-matched
control subjects from the group of healthy volunteers. All subjects in both
groups were Caucasians.
Results: The present study is demonstrated statistically significant differences in all frequency spectra of resting EEG between alcohol dependent
subjects and healthy volunteers. Alcohol dependent subjects had higher
beta power of resting EEG at all scalp location (p<0.05) prominently in
central regions (p<0.01) compared to control subjects. Our findings in
beta power are consistent with literary data. Alcohol dependent subjects
manifested lower theta power of resting EEG compared to control male
subjects at most electrode locations (p<0.001) . These data are inconsistent with literary sources. The alcohol dependent subjects showed higher
alpha power compared to control subjects at all electrode locations.
Conclusion: The results of present study support existing studies that
have reported an increase of beta power spectrum as an endophenotype
of genetically determined alcohol dependence. It is important to verify the
validity of this theory in Caucasian population. Hence, the beta power in
the EEG of children of alcoholic, especially before alcohol exposure, need
to be examined in middle-east European population.
References: 1.PORJESZ, B., BEGLEITER, H. Alcoholism and Human
Electrophysiology. In Alcohol research & health. 2003,vol. 27, No. 2, p.
153-160. 2.RANGASWAMY M, et al. Theta power in the EEG of alcoholics. In Alcohol Clin Exp Res. 2003, vol. 27(4), p. 607-615. 3.RANGASWAMY M, et al. Beta power in the EEG of alcoholics. In Biol
Psychiatry. 2002, vol. 52(8), p. 831-842.
P-01-08
Indices of oxidative stress in alcoholic patients in dynamic
of withdrawal syndrome stopping
Stanislav Terovsky
Nikolay Bokhan, Svetlana Ivanova, V. Safiullina, M. Abushayeva
Introduction: Investigations of influence of metabolic cerebroprotector
with antioxidant properties citoflavin on indices of peroxide oxidation of
lipids in erythrocytes and antioxidant properties of blood serum in alcoholic patients in withdrawal syndrome stopping.
Method: Group of examined was constituted from 23 alcoholic patients
aged 25-60 years; 15 patients complimentarily taking in citoflavin (basic
group) and 8 persons with the standard scheme of the therapy (group of
comparison). 30 healthy donors (control group).
Results: Assessment of biological indices of alcoholic patients was conducted in dynamic: before administration of the treatment against the
background of severe withdrawal syndrome and 10 days after the beginning the therapy. Level of oxidative stress was assessed according to concentration of end product of peroxide oxidation of lipids - malonic dialdehyde in erythrocytes. Integral assessment of antioxidant properties of
blood serum was identified in the test of induced chemiluminescence. In
erythrocytes of alcoholic patients in the state of withdrawal syndrome
increase of concentration of malonic dialdehyde as compared with control group has been found (p<0,01). In the process of used schemes of
the therapy reliable decrease of TBC-active products in erythrocytes of
patients has been revealed: in group with application of citoflavin content
of MDA before the therapy has constituted 59,50 3,17 mcmol/l, after
therapy 47,26 2,79 mcmol/l; p<0,05 (in control 38,71 1,17 mcmol/l),
in group of comparison decrease of the level of malonic dialdehyde from
55,59 5,09 mcmol/l to 45,30 5,62 mcmol/l; p>0,05 has been noticed.
Intensity of luminescence of serum in induction with peroxide is significantly higher what testifies to low antioxidant properties of blood serum
in alcoholic patients before the therapy as compared with normal values
of healthy persons (p<0,01). After therapy with citoflavin antioxidant
properties of serum of patients improved reliably (p<0,05), in group of
comparison a reliable improvement
94
Conclusion: Therapy with an antioxidant influences more efficaciously

clinical picture and alteration of the level of oxidant stress than standard
therapy.
P-01-09
Chronic schizophrenic and dissociative symptoms associated with ketamine abuse
Celia Morgan
University College London, Sub-Dept Clinical Health Psych, United
Kingdom
Huw Rees, H. Valerie Curran
Introduction: The glutamatergic model of schizophrenia is based partly
on the observation that an acute dose of the NMDA-receptor antagonist
ketamine induces psychotic like symptoms (e.g. Krystal et al., 1994).
Ketamine is also being used increasing illicitly by recreational drug users.
Phencyclidine (PCP), an NMDA-receptor antagonist similar to ketamine,
was found to cause protracted psychoses often lasting up to several
weeks following an acute dose (Ellison, 1995). It has also been suggested
that chronic NMDA-receptor antagonist administration may better model
some of the symptoms of schizophrenia than acute administration
(Jentsch & Roth, 1999). It was not known whether repeated self-administration of ketamine induces schizophrenic or any other psychiatric symptoms in recreational ketamine users.
Method: A total of 150 individuals were given mood and mental state
measures: 30 frequent ketamine users (mean 21.3 2.36 days per
month), 30 infrequent ketamine users (3.25 2.55 days per month),
30 ex-ketamine users, 30 poly-drug users and 30 non-drug users. The
mood and mental state measures used were: the Peters delusion inventory (PDI), the OLIFE (schizotypy), the Dissociative Experiences Scale (DES)
and the Spielberger Trait Anxiety Inventory (STAI) and Beck Depression
Inventory (BDI).
Results: Frequent ketamine users rated themselves has having significantly more Unusual Experiences on the OLIFE scale, which are akin to
positive symptoms in schizophrenia and they also scored more highly on
the PDI, which is an index of delusions. Frequent ketamine users demonstrated more dissociative symptoms on the DES and higher levels of
depression. Both frequent and infrequent ketamine users demonstrated
higher levels of Cognitive Disorganisation on the OLIFE scale than the
other groups, which is an analog of Thought Disorder in schizophrenia.
All the drug using groups showed higher levels of impulsivity on the OLIFE
Impulsive Non-Conformity sub-scale. There were no differences
between the groups in anxiety
Conclusion: Heavy ketamine users show a host of psychiatric like symptoms including delusions, depression and dissociation. Thought disorder
was present in both groups of current ketamine users. Whilst it is impossible to rule out pre-existing differences, the absence of any such symptoms in ex-ketamine users seems to suggest that these are related to current use of ketamine.
References: Krystal et al. (1994) Arch Gen Psych, 51: 199-214 Ellison
(1995) Brain Res Brain Res Rev, 20: 250-67 Jentsch & Roth (1999)
Neuropsychopharmacology, 20: 201-25
P-01-10
Alcohol dependence and acamprosate. How does it work?
Yuri Blednov
University of Texas, Waggoner Center for Alcohol an, Austin, USA
Adron Harris
Introduction: A camprosate is an abstinence-promoting drug widely
used in the treatment of alcohol dependence but which has an unknown
mechanism of action. Recently, this drug has been suggested to interact
with excitatory glutamatergic neurotransmission as an antagonist of the
metabotropic glutamate receptor subtype 5 (mGluR5) (see De Witte et al.,
2005 for rev.). We showed that mice lacking mGluR5 demonstrate the
reduced severity to acute ethanol-induced withdrawal (ACWITH) and
increased sensitivity to sedative (hypnotic) effect of ethanol (Blednov et
al., 2005).
Method: To evaluate possible connections between mGluR5, ethanolinduced behavior and pharmacological effects of acamprosate, we studied the effects of acamprosate on ACWITH and ethanol-induced loss of
righting reflex (LORR) in mGluR5 knockout mice. The effects of acamprosate were compared with a mGluR5 antagonist, MPEP.
Results: Only high (45 mg/kg) but not low (10 mg/kg) doses of MPEP significantly potentiated the LORR induced by injection of low dose of
ethanol (3.2 g/kg) in wild type mice. However, both doses of MPEP significantly reduced the severity of ACWITH in wild type mice. Only high
(300 mg/kg and 400 mg/kg) but not low (200 mg/kg) doses of acamprosate potentiated the LORR induced by injection of low dose of ethanol
(3.2 g/kg) in wild type mice. Both low (200 mg/kg) and high (300 mg/kg)
doses of acamprosate reduced the severity of ACWITH in wild type mice.
Similar with MPEP the protective effect of acamprosate on ACWITH was
found only when it was injected before but not after the injection of
ethanol. No effects of acamprosate or MPEP on ethanol-induced LORR
and ACWITH were found in mGluR5 knockout mice.
Conclusion: We show that the pharmacological effects of acamprosate
on ethanol-induced behavior (LORR and ACWITH) are similar to effects of
the selective mGluR5 antagonist MPEP. Moreover, no effects of acamprosate were found in mutant mice lacking the mGluR5 receptor. There
results support the hypothesis that effects of acamprosate on ethanolinduced behavior can be mediated by mGluR5 and selective antagonists
of mGluR5 can be useful for treatment of alcoholism.Supported by the
National Institute of Alcohol Abuse and Alcoholism, NIH (AA U01 13520INIA Project).
References: De Witte P, Littleton J, Parot P, Koob G. CNS Drugs.
2005;19(6):517-537. Blednov YA, Walker D, Harris RA. FASEB J. 2005; 19
(5) P875.2.
P-01-11
Relationship between alcohol consumption and sexual
activity in 18-25 years old university students
Francisco Bustamante
Universidad de los Andes, Medicine School, Santiago, Chile
Karl Schnellenkamp, Martin Valdebenito, Jorge Ferreira, Ernesto Donoso,
Andres Glasinovic
Introduction: Alcohol consumption and sexual activity, separately, are
risk behavior for students between 18 and 25 years old young adults in
our society. However, the association between both in Chile is not well
documented. This study was directed to establish the prevalence of (1)
alcohol consumption, (2) sexual activity (at least one lifetime sexual intercourse) and (3) the relationship between alcohol consumption and sexual
activity in university students
Method: A random sample of 855 single students between 18 and 25
years old was obtained from two universities. A self-applied, anonymous
survey was employed, using AUDIT (Alcohol Use Disorders Identification
Test) and questions about sexual behaviors. These results were analyzed
using STATA and SPSS
Results: 89.4% of young adults who answered the survey drinks alcohol,
and the prevalence found for problem drinking was 10.7%. Sexual activity was positive in 55.9%, where the mean age of start was 17.5 years
old and promiscuity was present in 17.4% of the students. A statistically
significant association was found between alcohol consumption and sexual activity. An Odds Ratio increased in 4.8 and 8.4 times (2.2 to 10.6 and
3.2 to 22.5) was found in those with harmful use (AUDIT = 16-19) and
alcohol dependence (AUDIT > 20), respectively, for having at least one
sexual intercourse, compared with no risk alcohol consumption (AUDIT
<8) with 95% Confidence Level (CL). There is a higher probability of
promiscuity when the alcohol use is higher (Spearman = 0.37 in AUDIT 815 vs Spearman = 0.69 in AUDIT > 20)
Conclusion: The majority of college students drinks alcohol and more

than half have done sexual intercourse, existing a significant association
between both of them. We also conclude that a higher alcohol use is
related with a younger age of start in sexual activity and promiscuity in
university students between ages 18 and 25. It would be interesting to
test the dopaminergic function in people with both sexual promiscuity
and alcohol abuse, because dopamine is very important for the reward
system and could explain this cross over behavior.
References: - Hingson R. Early age of first drunkenness as a factor in college students unplanned and unprotected sex attributable to drinking.
Pediatrics 2003; 111:34-41
P-21
Addictive Disorders II
P-21-01
Chronic effects of ketamine on cognitive function
H. Valerie Curran
University College London, Sub Dept Clinical Health Psych, Germany
Huw Rees, Celia Morgan
Introduction: Ketamine abuse is on the increase worldwide (Drugscope,
2005; DAWN, 2004). Ketamine is an antagonist of the NMDA-receptor
and a single dose of the drug in the laboratory has been shown to impair
memory and cognition (e.g. Newcomer et al., 2001). Preliminary research
has also indicated that recreational ketamine use may be associated with
some cognitive impairments (Morgan et al., 2004) however no large scale
studies of this drug using population had been conducted. Preclinical evidence suggests some reversible neurotoxicity in animals following repeated NMDA-antagonist administration (Olney et al., 1997), however it is not
known whether this is reversible upon cessation of use of the drug.
Method: A total of 150 individuals were tested on a battery of cognitive
tasks: 30 frequent ketamine users (mean 21.3 2.36 days per month),
30 infrequent ketamine users (3.25 2.55 days per month), 30 ex-ketamine users, 30 poly-drug users and 30 non-drug users. Cognitive tasks
included spatial working memory, pattern recognition memory, the
Stockings of Cambridge (a variant of the Tower of London task), 0-back
component of the N-back task and verbal and category fluency.
Results: Frequent ketamine users were impaired on the spatial working
memory, pattern recognition memory, Stockings of Cambridge and category fluency, however they exhibited preserved verbal fluency and attention (as indexed by the 0-back task). There were no differences in the performance of the infrequent ketamine users or ex-ketamine users compared to the other groups.
Conclusion: Frequent ketamine use leads to impairments in working
memory, episodic memory and aspects of executive function. Recreational
ketamine use does not appear to be associated with distinct cognitive
impairments. The cognitive impairments observed in the frequent ketamine
group may be reversible upon cessation of ketamine use as no performance decrements weVre observed in the ex-ketamine users.
References: Morgan et al. (2004) Drug Alc Depend, 75:301-08 Olney et
al. (1997) Arch Neurol, 54: 1234-40
95
P-21-02
Cognitive and subjective effects of the acute MDMA both
alone and in combination with alcohol
P-21-04
Cannabis use of schizophrenic opiate addict patients in
methadone maintenance treatment (mmt)
H. Valerie Curran
University College London, Sub Dept. Clinical Health Psych, UK
Alison Whitty, Celia Morgan, John Henry
Einat Peles
Adelson Clinic for Drug Abuse, Treatment and Research, Tel Aviv, Israel
Shaul Schreiber, Miriam Adelson
S. Schreiber, M. Adelson
Introduction: Although MDMA ((3,4-methylenedioxymethamphetamine,

ecstasy) is often taken along with alcohol, little is known about how this
combination influences cognitive function, mood or the desire to engage
in further drug use. This study therefore aimed to determine the effects
of MDMA and alcohol, both alone and in combination.
Method: a double-blind, cross-over design was used to compare the
effects of 80 mg MDMA, 0.5 mg/kg ethanol, their combination and
placebo. Participants were 12 healthy males who had taken ecstasy previously between 3 and 20 times. They attended on four study days each
separated by a two week washout. They were assessed on cognitive,
psychomotor, mood and subjective reinforcement measures over a period
of 6 hours.
Results: MDMA significantly impaired performance on a verbal learning
task (Bushke selective reminding), pattern recognition, spatial working
memory and accuracy in rapid visual information processing. The effects
of the MDMA/alcohol combination on those tasks was not significantly
different from that of MDMA alone. However the combination did lead
to greater impairment of focussed attention than either treatment alone.
Further, simple motor speed was increased by MDMA and reduced by
alcohol whilst the combination cancelled out and did not differ from
placebo. MDMA increased ratings of empathy, euphoria and anxiety as
well as suppressed appetite. Participants felt less tipsy after the combination than after alcohol alone. The combination led to increased ratings of
want more alcohol compared with other treatments. All effects were
most marked at 45 and 120 minutes post-drug and by 4 hours were generally no different from placebo levels. The combination of MDMA and
alcohol was liked more than the effects of either individual treatment.
Conclusion: MDMA adversely affects spatial working memory, verbal
and visual episodic memory and its combination with this dose of alcohol
was not significantly more detrimental than MDMA alone. Our findings
suggest that MDMA can reduce the tipsiness felt after alcohol & increase
the desire for further alcohol consumption. The combination of alcohol
and MDMA is more subjectively appealing to volunteers than either drug
alone.
P-21-03
Nicotine use and its correlates in patients with psychosis
Sten Levander
Lund University, Department of Clinical Science, Malm, Sweden
Jonas Eberhard, Eva Lindstrm
Introduction: To examine nicotine use and its correlates among psychotic
patients.
Method: Longitudinal naturalistic study of 176 patients, diagnosed with
schizophrenia or schizophrenia-related psychotic disorders, and treated
with risperidone at study entry. Levels of nicotine abuse (smoking/chewing tobacco, snuffing) were measured along with other relevant ratings
and measurements (symptoms, drug treatment, side effects, weight, cognitive function and outcome) at baseline and once yearly for 5 years.
Results: Nicotine use was twice as common as in the general population.
Only few nicotine users had started after onset of psychoses. We could
not find any differences among nicotine users and non-users in diagnosis,
symptoms, side effects, weight, cognitive functions and outcome, crosssectionally and longitudinally, ruling for or against the self-medication
hypothesis.
Conclusion: A parsimonious interpretation of the findings appears to be
that patients suffering from psychosis rather fail to desist from nicotine
than experience positive effects of the usage.
96
Introduction: Cannabis use was found to be associated with

Schizophrenia. We studied whether cannabis use characterized schizophrenic opiate addicts, and to their MMT outcome (retention).
Method: Schizophrenic and non schizophrenic opiate addict patients
from a cohort of all 546 patients admitted to our MMT program between
25/June/1993- and 24/June/2005 and followed them up until June 2006
were compared. Lifetime psychiatric diagnosis was done. Cannabis, benzodiazepines, opiates, cocaine, and amphetamines on first month and
month 13 were studied, and defined positive if at least one urine result
was positive. Kaplan Meier and Cox models were used for cumulative
retention.
Results: Of the 546 patients, mean admission age was 37.18.6 and
26.9% were females. Thirty-three (6%) patients were diagnosed with
schizophrenia, 178 had other DSM-IV Axis I diagnosis, 288 had no DSMIV Axis I diagnosis and 39 had no DSM-IV Axis I & II diagnosis. Cannabis
use on admission to MMT was in 21.2% of the 33 schizophrenic patients,
and 11.9%, 10.8% and 7.7%- of the three other groups respectively.
Cocaine was lower in the schizophrenic (3%) vs. non schizophrenic
(17.5%, p=0.03), with no differences in amphetamines (15.2% vs.
8.5%), and benzodiazepines (66.7% vs. 56.2%). Net reduction (proportion of those who stopped minus proportion of those who started) was
23.3% in schizophrenic and 45.7% in others. One year retention in treatment was similar between schizophrenic (78.8%) and others (76.6%).
Cumulative retention was similar between schizophrenic (6y, 95%CI 4.27.9y) and non schizophrenic (5.9y, 95%CI 5.4-6.4y) groups, and was not
related to cannabis use on admission. However, while the non schizophrenic group with positive urine for cannabis after one year had lower
cumulative retention 5.1y (95%CI 4.1-6.1) vs. the non-schizophrenic negative cannabis group 6.8y (95%CI 6.2-7.4, p=0.03), there was no difference between positive 5.9y (95%CI 2.5-9.4) vs. negative 5.9y (95%CI
3.8-8.0) cannabis schizophrenic groups. Schizophrenic patients did not
differ from others in gender distribution and age on admission.
Conclusion: The schizophrenic patients had similar outcome as other
patients. They had shown a trend of higher rate of cannabis use on
admission, and their cannabis use in treatment (after one year) did not
deteriorate their long term retention as it did in non-schizophrenic
patients. These findings support the possibility that cannabis use in opiate
dependent schizophrenic patients may be associated with a self medication pattern.
P-21-05
The relationship between loneliness and Internet use and
abuse
Cristinel Stefanescu
IASI, Romania
Gabriela Chele, Roxana Chirita, Vasile Chirita, Mircea Ilinca
Introduction: The computer has provided some wonderful opportunities
for our children. Never before have had they had access to such a powerful tool for conducting school research, learning about new things,
finding new recreation and entertainment, and communicating with their
friends.
Method: The purpose of this paper was to study how Internet use relates
to psychological well-being, perceptions of online romantic relationships,
the self and identity. High school students (N = 283) completed a questionnaire including measures of time spent online, pathological
Internet use, loneliness and relationship quality.
Results: The following results are divided into two sections. First, we consider the relationship between Internet use, Internet motivation and loneliness. Second, we present results on the differences in relationship quality between online and face-to-face relations.
Conclusion: Our results showed a significant positive correlation

between measures of Internet use and loneliness. As well, face-to-face
relationships were rated higher on both positive and negative quality
dimensions relative to online relationships. Finally, Internet use was associated with identity status. These results suggest that the Internet may be
an important aid for teenager as they searched for an young identity.
References: 1. Greenfield D.N.: The Net Effect: Internet Addiction and
Compulsive Internet Use, 2000. Available: http://www.virtualaddiction.com 2. Subrahmanyam, K., Greenfield, P., Kraut, R., & Gross E.,
The impact of computer use on childrens and adolescents development.
Applied Developmental Psychology, 22, 7-30, 2001.
P-21-06
The effects of progesterone on the reinstatement of cocaineseeking behavior in female rats
Justin Anker
University of Minnesota, Psychiatry, Minneapolis, USA
E. B. Larson, L. A. Gliddon, M. E. Carroll
Introduction: Phase of estrous cycle has been implicated in fluctuations
in the reinforcing effects of cocaine. Estrogen has been shown to facilitate the acquisition and reinstatement of cocaine self-administration
when administered to ovariectomized (OVX) rats. Recently, it has been
shown that progesterone (PROG) may decrease the rate of cocaine acquisition in female rats. The purpose of the present experiments was to
expand upon these earlier findings by studying the effects of estrogen
(estradiol benzoate, EB) and PROG on the escalation (Experiment 1) and
reinstatement (Experiment 2) of cocaine-seeking behavior in female rats.
Method: Rats were implanted with i.v. catheters and either received a
bilateral ovariectomy or a sham operation (SHAM). Following surgery they
were placed in operant chambers and trained to lever press for 0.4 mg/kg
cocaine infusions under a FR 1, 20-sec timeout schedule of reinforcement
during daily 2-hr sessions. In Experiment 1, vehicle, EB, and/or PROG
treatments began after surgery (2 days) and were administered daily until
the completion of the study. The session length was extended to 6-hrs
after rats stabilized cocaine intake. Self-administration (S-A) and infusions
were subsequently monitored for 21-days during the long access sessions
to allow for group comparison in the escalation of cocaine S-A. After the
21-day escalation phase, responses and infusions under the short-access
(2-hr) condition were reassessed. In Experiment 2, after the acquisition of
cocaine S-A, rats were maintained at the 0.4 mg/kg cocaine dose for
14 consecutive 2-hr sessions. After the 14th day of maintenance cocaine
was replaced by saline and a 21-day extinction phase commenced. At the
end of extinction vehicle, EB, and/or PROG were administered until the
completion of the study. Three days following the extinction period the
2-day reinstatement procedure commenced. On the first day saline was
injected intraperitoneally at the beginning of the 2-hr session and on the
following day a 10 mg/kg cocaine injection was administered.
Results: Estrogen facilitated while PROG and OVX attenuated cocaine
seeking during escalation (Experiment 1) and reinstatement (Experiment 2).
OVX decreased cocaine-seeking behavior during escalation and reinstatement while the administration of EB in OVX rats produced levels of
responding comparable to those seen in the SHAM groups. The administration of PROG in OVX+EB and SHAM operated rats attenuated the
escalation and reinstatement of cocaine seeking relative to the non-PROG
treated groups.
Conclusion: The suppression of cocaine-induced escalation and reinstatement following the administration of PROG suggests a possible role
for PROG in the prevention of cocaine abuse during critical phases of
drug abuse in female cocaine users.
and anonymity. Studies of general Internet users suggest that some childrens may experience psychological problems such as social isolation,
depression, loneliness, and time mismanagement related to their Internet
use and failure at school.
Method: The purpose of this study is to investigate issues related to
Internet use by school students from 11 to 18 years old. The survey
included a representative sample of 650 school students of ages 11 to 18.
All of the students came from 7 gymnasium schools and 6 high schools
of Iasi, Romania. The students answered to a questionnaire comprising
34 questions related to computer activities. These were aimed at highlighting: 1. The frequency of Internet use by the students; 2. The identification of a possible psychological problems; 3. The identification of a possible Internet addiction.
Results: The data was processed using the SPSS statistics software,
version 11.0. Results show that the school students prefer to spend a considerable amount of time with their computers, over 5 hours/day. This
study tried to identify aspects of Internet addiction in gymnasium and
high school students, as well. The survey reveal that amount of time spent
online for the Internet are positively related to more psychological problems.
Conclusion: Excessive amounts of time at a computer can contribute to
undeveloped social skills and a form of addictive behaviour, and failure at
school.
References: 1. Young K. et al.: Cyber-Disorders: The mental Health
Concern for the New Millennium: CyberPsychology and Behavior, vol.3,
nr. 1,1999 2. Subrahmanyam, K., Greenfield, P., Kraut, R., & Gross, E. The
impact of computer use on childrens and adolescents development.
Applied Developmental Psychology, 22, 7-30, 2001.
P-21-08
Aripiprazole inhibits acute self-administration of cocaine
but is not self-administered in drug nave mice
Gunnar Sorensen
Rigshospitalet Univ. Hosp., Laboratory of Neuropsychiatry, Copenhagen,
Denmark
Thomas Sager, Lise Tottrup Brennum, Gitta Wrtwein, Anders FinkJensen, David Woldbye
Introduction: The antipsychotic compound aripiprazole is a partial agonist at dopamine D2 receptors and may consequently be used as a new
therapeutic agent in drug abuse. To this end, we tested the ability of aripiprazole to block self-administration of cocaine in drug naive mice using a
single-session procedure. We also tested whether mice would acutely
self-administer aripiprazole.
Method: Male NMRI mice were placed in self-administration boxes and
an injection needle was inserted into the tail vein. Nose-pokes resulted in
the delivery of cocaine or 0.9% saline infusions under a fixed ratio 1 (FR1)
schedule of reinforcement with no time-out. Aripiprazole was administered p.o. two hours prior to the self-administration session. In addition,
aripiprazole was tested in the acute self-administration model at doses of
0.0003-0.3 mg/kg/infusion.
Results: Oral administration of aripiprazole at both 0.2 and 0.4 mg/kg
significantly reduced i.v. self-administration of cocaine in a dose-dependent manner. Aripiprazole i.v. did not cause higher nose-poking frequencies per se as compared to vehicle at any dose tested.
Conclusion: Aripiprazole decreased the acute self-administration of
cocaine, but did not seem to have acute reinforcing properties per se. The
results indicate a potential role of aripiprazole in the medical treatment of
drug abuse.
P-21-09
Treating cocaine cravings with quetiapine
P-21-07
Impact of Internet use on children and teenagers
Roxana Chirita
Eli Lilly Romania, Bucharest, Romania
Vasile Chirita, Cristinel Stefanescu, Mircea Ilinca, Gabriela Chele
Introduction: The Internet has a significant potential for providing children and youth with access to educational information. However, it can
become an escape from reality that has the appearance of safety, intimacy
Andre Tapp
VA Puget Sound Health Care Sys, American Lake Div. (A-116-R),
Tacoma, USA
Amanda Wood, Annette Kennedy, Andrew Saxon
Introduction: Cocaine addiction is difficult to treat with no approved
pharmacological options. The high relapse rate may be related to continued cravings for cocaine even after abstinence. In preliminary reports, the
atypical antipsychotic quetiapine has shown promise for the treatment of
97
substance abuse disorders. The primary objective of the current study was
to assess the efficacy of quetiapine in reducing cocaine cravings and use
in non-psychotic subjects with cocaine dependence.
Method: Twenty-two cocaine dependent, non-psychotic men were initiated to open-label treatment with quetiapine (300-600 mg/day dependent on medication tolerance) over six weeks. The primary outcome measure was weekly self-report of cocaine cravings as assessed with the Brief
Substance Craving Scale (BSCS). Cocaine use was captured with a selfreport Timeline Followback calendar, administered every two weeks.
Results: The mean dose of quetiapine after stabilization was 429mg/day
(S.D. = 122). Intent-to-treat regression analyses indicated that the BSCS
total score decreased significantly over time ( = -.54; 95% CI = -.81, .28; p < 0.001). Self-reported quantity of cocaine used also decreased
over time ( = -.15; 95% CI = -.29, -.02; p < 0.05).
Conclusion: Open-label quetiapine treatment reduced cocaine cravings
and the use of cocaine in non-psychotic individuals with cocaine dependence. Additional research is needed to confirm the current findings and
to further delineate the role quetiapine may play in the treatment of
cocaine use disorders.
References: Brown ES, Nejtek VA, Perantie DC, et al. Quetiapine in bipolar disorder and cocaine dependence. Bipolar Disord 2002; 4:406-411.
Sattar SP, Bhatia SC, Petty F. Potential benefits of quetiapine in the treatment of substance dependence disorders. J Psychiatry Neurosci, 2004;
29:452-457.
P-21-10
Nicotine and ethanol activate PKA signaling synergistically
in nucleus accumbens/ventral tegmental co-cultures
Yuichiro Inoue
Nara Medical University, Dept of Psychiatry, Kashihara, Japan
Woodward F. Hopf, Makoto Inoue, Sawako Inoue, Soichiro Kitamura,
Yamato Wada, Toshifumi Kishimoto, Antonello Bonci, Ivan Diamond,
Lina Yao
Introduction: Tobacco and alcohol are most widely used and show serious co-morbidity. The mesolimbic dopamine system mediates nicotine
and ethanol reinforcement, but the responsible cell signaling mechanisms
are poorly understood. Nicotinic acetylcholine receptors (nAChRs) are
highly expressed on ventral tegmental midbrain dopamine (VTA) neurons,
with relatively low expression in nucleus accumbens striatal (NAcb) neurons. Dopamine receptors (D1 and D2) are expressed on NAcb neurons.
Thus, nicotine could affect NAcb neurons indirectly by activating VTA neurons and releasing dopamine in the NAcb.
Method: We established primary cultures containing neurons from VTA
or NAcb alone or as co-cultures. CRE-mediated gene expression was
determined as an indirect indicator of neuronal activity using
HSVLacZ/CRE-Luciferase viral vectors.
Results: Nicotine increased CRE-mediated gene expression only in cocultures; this increase was blocked by nAChR or dopamine receptor
antagonists. Further, low concentrations of nicotine and ethanol in combination only increased gene expression in co-cultures, and this increase
was blocked by by nACh, D2, or adenosine A2 receptor antagonists, Gbg
or protein kinase A (PKA) inhibitors, and adenosine deaminase.
Conclusion: These results suggest that nicotine activated midbrain neurons, causing release of dopamine which stimulated dopamine receptors
on striatal neurons, and that low concentrations of nicotine and ethanol
in combination activated striatal neurons through combination between
dopamine and adenosine receptors. These data may provide a novel cellular mechanism, whereby combined use of tobacco and alcohol may
enhance the reinforcing effect in humans, increasing the risk for developing co-addiction.
98
P-21-11
Proliferation of drug dependence in Ukraine from the
point of view of population ecology
Igor Linsky
INPN AMS of Ukraine, Treatment of Drug Addictions, Kharkov, Ukraine
Alexander Minko, Edward Pervomaysky, Liliya Dyachenko, Alexey Minko
Introduction: There are numerous evidences of the fact that process of
proliferation of drug dependence has much in common with development of any population. So, for example, the involving in drug intake of
new consumers is an equivalent of reproduction; counteraction of a society to the further distribution of dependence on drugs is an equivalent of
adverse conditions of an environment; and the market of drugs is an
equivalent of a forage reserve. Therefore, the purpose of research is the
research of opportunities for description of long-term dynamics of the
epidemiological parameters of drug dependence in Ukraine by tools of
population ecologies, namely by Verhulst equation (VE) which describes
development of a population in conditions constraining its growth [1].
Method: Data about proliferation of drug addiction in 1970-2003 have
been taken from official annual reports of Ministry of Health of Ukraine
[2] and fitted by VE: n = mn - rn2 where: n - the current number of a
population (in this case is the current prevalence of drug addiction); n an increment of number of a population (in this case is an increment of
prevalence of drug addiction); m and r - quotients, which have been calculated by least-squares method on computer.
Results: It is established, that dynamics of proliferation of drug addiction
in Ukraine in system of coordinates prevalence - increment of prevalence looks like a classical parabola and consequently is well fitted by VE.
This equation also well describes dynamics of proliferation of drug addiction in separate regions of Ukraine.
Conclusion: Fitting of the real epidemiological data received during long
enough period of time by VE, enables to make forecasts, concerning maximal prevalence of drug addiction in given regions or in whole country.
References: 1. Verhulst P.F, Notice sur la loi que la population suit dans
son accroissement // Corrispondence mathematique et physique publiee
par A. Qutelet (Brussels-1838). 2. Parameters of populations health and
use of resources of public health services in Ukraine for (1991-2003) year.
// Collection of Ministry of Public Health of Ukraine. - Kiev (1992-2004).
P-21-12
Everyday prospective memory impairments associated
with teenager drinking
Terence ONeill
Northumbria University, Psychology, Newcastle-Upon-Tyne, United
Kingdom
Introduction: Alcohol is on of the most commonly used substances by
teenagers in the UK. Despite this, little research has investigated the possibility of deficits in prospective memory (PM) ability (memory for future
intentions) being associated with excessive alcohol use in teenagers. The
present study aims to address this by comparing excessive drinkers with
low-dose/alcohol-free teenagers aged between 16-19 years on self-reported everyday PM. whilst controlling for age, the use of strategies to assist
remembering, and other substance use.
Methods: A non-experimental design was used. An opportunity sample
of 108 students studying at College/University in the North East of
England participated. 45 participants were identified as 'excessive alcohol
users' (ingesting above 21/14 units of alcohol per week for males/females respectively over a period of 1 year or more) and 63 were identified as
'low dose/no-alcohol controls' (ingesting below the 21/14 units over
1 year or more (incorporating 9 non-users). Each participant completed
the self-report Prospective Memory Questionnaire (PMQ) which measures everyday memory lapses (eg how often one forgets to post a letter,
lock ones door, etc.) and a Substance Use Questionnaire which was
used to measure weekly alcohol use and other substance use.
Results: A series of one-way ANOVAs revealed that the excessive alcohol
user group was older, smoked more cigarettes and used more cannabis,
than the control group, with no difference in strategy use. A MANCOVA
revealed that, after controlling for age, cigarette use and cannabis use,
the excessive alcohol user group reported significantly more long-term,
short-term and internally-cued, PM lapses.
Conclusion: Deficits in everyday PM are associated with excessive drinking in teenagers.
P-21-13
Identity and the internet addiction on Romanian teenagers
Vasile Chirita
Eli Lilly Romania, Bucharest, Romania
Roxana Chirita, Cristinel Stefanescu, Gabriela Chele, Mircea Ilinca
Introduction: Identity is the result of the process through which the individual assumes social values, shared norms of behaviour and knowledge
which allow the individual to feel part of a social group and at the same
time, allow him to be recognized. Personal identity and social identity are
meanings which grow within the context of relationships that characterize
the individuals life.
Method: The following study was designed to be a preliminary investigation into various aspects of Internet use among high school students. The
survey included a representative sample of 356 school students of ages
14 to 18. All of the students came from 7 high schools of Iasi, Romania.
The students answered to a questionnaire comprising 34 questions related to internet activities. These were aimed at highlighting: 1.The frequency
of internet use by the students; 2. The interference of excessive use with
academic performance, socialization, personality; 3. The identification of
a possible pathological internet use. The data was processed using the
SPSS statistics software, version 11.0.
Results: Results show that the school students prefer to spend a considerable amount of time with their computers, over 5 hours/day. The purpose of this article is to describe how internet use affect socialization, academic performance, personality and to discuss how identity are constructed
in cyberspace.
Conclusion: Some researchers have argued that the Internet provides a
community to belong to as other more traditional types of communities
are breaking down through urbanization and other social changes. It has
been suggested that people with low selfesteem turn to the Internet to
reduce the chances of rejection, to find support, and to discuss their emotions. Other scholars have suggested that the appeal of the Internet lies
in the possibility it offers to construct a new identity for oneself.
References: North T. (1995) Internet and use net global computer networks, an investigation of their culture and its effect on new users in
higher education. Masters Thesis, Carlin University, http//foo.curtin.edu.au/thesis/default.html Rheingold H. (1993) The virtual community.
Homesteading on electronic frontier. New York, HarperPerennial
99
AFFECTIVE DISORDERS (BIPOLAR) - Poster
P-22
Affective Disorders (Bipolar)
Conclusion: 1. Quetiapine and olanzapinum in association with valproate

could possibly be an effective treatment for rapid cycling bipolar patients.
2. Adequate doses for acute episodes could significantly differ according
to the episode polarity and the length of treatment.
P-22-01
Searching for mendelian markers for bipolar disorder
P-22-03
Use of Lithium during pregnancy: A clinical decision analysis
Maria Soledad Calvo Prandi

Malloco, Chile
Carlos Gomez-Restrepo
Universidad Javeriana, Cundinamarca, Bogota, Colombia
Ricardo Sanchez Pedraza, Alvaro Camacho
Introduction: Bipolar Disorder (BD) is one of the most important psychiatric disorders. Etiopathogenis is still unknown; nevertheless there is widely
recognized genetic component. Many hypotheses have been proposed
but, it is necessary to search for Mendelian markers to build a theory.
Method: Bibliographical research was realized on molecular aspects of
the BP, between 2000 to 2006, across the web site: http: // www.sciencedirect.com/college.
Results: One of the hypotheses involves genes participating in signal
transduction responsible for plasticity. Some of these: Glycogen Synthase
Kinase 3- (GSK-3), regulates glucose utilization: lithiums therapeutic
effect is exerted as its inhibitor (Chen et al, 1999). Homozygous patients
for the wild allele didnt show changes in the relapse index, on the other
hand patients carrying the mutant decreased the relapse index when both
groups where under lithium (Benedetti et al, 2005). Even more, GSK-3
can be under regulation by the monoaminergic system, involved in BD
(Kato, 2001). Protein Kinase C (PKC), abundant in the Central Nervous
(CNS). Its secondary messenger is also altered by lithium treatment
(Berrindge, 1989). CPK activation results in a manic effect while its inhibition produces an antimanic effect. (Einat & Manji, 2006). Glutamate
receptors the most important excitatory pathway of the CNS, responsible
for opening Ca+2 channels. They are involved in memory and learning
(Tashiro et al, 2006) and plasticity. Lithium diminishes the presence of
GLUR1 sub-unit and inductor drug increases the presence of this receptor
(Du et al, 2004), whereas heightened stimulators of these receptors are
antidepressant (Li et al, 2001).
Conclusion: To establish in a Chilean sample: i) the probable existence of
a polymorphism in the promoter of the GSK-3B gene and if clinical behavior correlates with that described in the caucasian sample and, ii) to
explore the possibility of polymorphism and clinical behavior for the genes
to PKC isoenzymes and for the subunit GLUR1 of the AMPA receptor.
References: Chen et al, (1999), J Neurochem 72;1327. Benedetti et al.
(2005), Neurosc Letters 376;51 Kato (2001), Neurosc Res 40;105
Berrindge (1989), JAMA 262;1834. Einat y Manji (2006), Biol Psychiatry
XX;XXX (on-line) Tashiro et al. (2006), Nature 442;929. Du et al. (2004),
J Neurosc 24;6578. Li et al. (2001), Neuropharmacology 40;1028
P-22-02
Quetiapine and olanzapine in the treatment of rapid
cycling bipolar disorder (RCBD)
Adela Magdalena Ciobanu
Umf Carol Davila Bucharest, Psychiatry, Romania
Introduction: The objective of this study was to evaluate the
efficacy,safety and tolerability of quetiapine and olanzapine in association
with valproate in the treatment of rapid cycling bipolar disorder.
Method: 30 patients diagnosed with rapid cycling bipolar disorder by
DSM IV criteria were divided in 2 groups:15 patients treated with quetiapine 600-800mg/day and 15 patients treated with olanzapinum
10-15 mg/day. All the 2 groups received valproate 500mg/day. At the
beginning of the study, 12 patients were maniac, 8 were in a mixed state,
7 were depressed,3 were hypomaniac. Period of study - 1 year. Patients
were assessed with Clinical Global Impression Scale for Bipolars (CGI-BP),
the Young Mania Rating Scale (YMRS) and the Hamilton Depression
Rating Scale (HDRS). We evaluated all 2 group at baseline, after 1 week,
2 week, and every month during the period of study.
Results: 1. A similar and significant improvement was observed in both
group for all the scale scores (CGIBP,YMRS,HDRS) 2. Doses of quetiapine
and olanzapinum were significantly reduced by the end of the study in
compare with baseline. 3. Doses of quetiapine and olanzapinum differed
according to the initial episode 4. No relapse was reported during the
period study.
100
Introduction: Decision analysis is a useful tool in clinical practice, which

has rarely been used in psychiatry. Decision analysis entails assigning utilities or specific values to each outcome with the participation of the clinician and the patient Objective: To exemplify a decision making model in
a pregnant patient with bipolar disorder.
Method: Four decision trees with corresponding assigned utilities and
analyzed probabilities are presented. In each decision tree, 12 different
utilities or desired outcomes are assigned which were agreed upon by
both, clinician and patient. Measurements: Sensitivity analyses were conducted in the four different decision trees to inform the patient to continue
or discontinue lithium treatment during pregnancy.
Results: Based on our decision analysis, the final outcomes favored continuation of lithium therapy. These results were consistent in the four different decision trees.
Conclusion: This analytical tool offers a method to inform important
decisions for both patients and psychiatrist in those clinical scenarios
where there is a fine line between the risks and benefits of a given treatment.
References: Investigacion Clinica: Epidemiologia Clinica Aplicada. Ed.
Ruiz A, Gomez C, Londono D. Centro Ed. Javeriano Ceja. Primera Ed.
2001.
P-22-04
Neuropsychological functioning in offspring of bipolar
mothers
Danielle Bio
HCFMUSP, Mood Disorder Unit (GRUDA), Sao Paulo, Brazil
Cristiana Rocca, Sandra Petresco, Renata Krelling, Elisa Gutt, Ricardo
Moreno
Introduction: : Studies about bipolar disorder in children and adolescents
show that these patients present cognitive deficits in executive function,
attention and memory. There is an interest in assessing these same cognitive functions in children of parents with Bipolar Disorder. Objective: The
present research aimed to verify the neuropsychological functioning in
offspring of bipolar mothers, in order to establish if there is a standard of
deficits in this population, compared to a control group (offspring of
mothers without psychiatric pathology).
Method: : The offspring of 08 patients with bipolar disorder were evaluated at the Mood Disorder Unit (GRUDA) of the Institute and Department
of Psychiatry of the Clinical Hospital, School of medicine, University of Sao
Paulo and the offspring of 08 patients without psychiatric disorder of the
Gynecology General Clinic. A neuropsychological battery to assess attention, memory and executive function, composed by the following tests
was applied: Digit Span (WAIS/WISC), Finger Windows (WRAML),
Number / Letter (WRAML), Picture Memory (WRAML), Verbal Learning
(WRAML), Story Memory (WRAML), Sentence Memory (WRAML), Design
Memory (WRAML), Visual Learning (WRAML), Rey-Osterrieth Complex
Figure Test, Picture Arrangement (WAIS/WISC), Trail Making Test,
Wisconsin Card Sorting Test, Stroop Color Word Test. The groups were
matched by age, study level, sex and intellectual measure.
Results: The experimental group showed worse performance on the
Finger Windows, Picture Arrangement, Design Memory, Stroop - Card 3
and category do WCST compared to control group.
Conclusion: According to other studies, our findings suggest that experimental group presents visuospatial deficits.
References: DelBello MP, Geller B. Review of studies of child and adolescent offspring of bipolar parents. Bipolar Disorders. 2001; 3: 325-34.
McDonough-Ryan P, DelBello M, Shear PK, Ris MD, Soutullo C,
Strakowski SM. Academic and cognitive abilities in children of parents

with bipolar disorder: atest of nonverbal learning disability model. Journal
of Clinical and Experimental Neuropsychology. 2002; 24 (3): 280-5
Sheslow D, Adams W. Wide Range Assessment of Memory and Learning.
Wilmington: Wide Range Inc.; 1990. Spreen O, Strauss E. A Compendium
of neuropsychological tests. Oxford: Oxford University Press; 1998.
Wechsler D. Wechsler Intelligence Scale for Children - Third Edition. San
Antonio, TX: Psychological Corporation; 1991. Wechsler D. Wechsler
Intelligence Scale - Revised. New York: Psychological Corporation; 1981.
Wechsler D. Wechsler Abbreviated Scale of Intelligence. New York:
Psychological Corporation; 1999.
P-22-05
The effect of olanzapine on brain metabolism
Michael Koppitz
LKH Graz, Psychiatry, Austria
Markus Magnet, Anna Hdl, Roland Fian, Peter Hofmann, Hans Peter
Kapfhammer, Raphael Maria Bonelli
Introduction: Olanzapine is successfully used in the treatment of bipolar
disorder. Although some details are understood the mechanism of action
of olanzapine in brain metabolism is unkown. The aim of this study was
to investigate the influence of olanzapine on the metabolism of N-acetylaspartate (NAA), creatine (Cr), choline (Cho), myoinositol (mI), glucose
(Glc) and glutamate (Gln) in the basal ganglia in bipolar patients in comparison with healthy volunteers, using 1H-MRS (proton magnetic resonance spectroscopy). Another aim is to find a specific signature of bipolar disorder.
Method: 22 in-patients with DSM-IV diagnosed bipolar disorder and
17 healthy controls were scanned in a 1.5 Tesla SIEMENS MAGNETOM.
We looked for alterations in the metabolite ratios of NAA/Cr, Cho/Cr,
mI/Cr, and (Glc+Gln)/Cr. The acquired spectra were analyzed using
LCModel by Steven Provencher. The data were analyzed with independent samples T Test Group statistics using SPSS 14.0.
Results: Olanzapine increases the relative metabolite concentrations of
NAA/Cr (10,28%, p=0.035) and Cho/Cr (18,8%, p=0.008) in bipolar
patients compared to healthy controls. There is no influence of olanzapine
on mI/Cr and (Glc+Gln)/Cr. Bipolar patients without olanzapine and
healthy subjects have no significant difference in the relative metabolite
concentrations.
Conclusion: According to our findings olanzapine seems to increase
NAA/Cr and Cho/Cr ratios in bipolar patients that may indicate a neuroprotective function of olanzapine. This could contribute to understand
the mechanism of action as other studies report decreased NAA/Cr ratios
in bipolar patients. Further studies with larger samples should be done to
examine whether there is difference between untreated bipolar patients
and healthy subjects, preferred on a 3 Tesla scanner to get a better spectral resolution.
P-22-06
Asenapine reverses anhedonia induced by chronic mild
stress but displays no hedonic effects in an intracranial
self-stimulation protocol
Hugh M. Marston
Organon Laboratories Ltd, Department of Pharmacology, Lanarkshire,
United Kingdom
Mariusz Papp, Frederick D. C. Martin, Lisa H. Gold, Mohammed Shahid,
Erik H. F. Wong
Introduction: The effects of asenapine, a novel psychopharmacologic
agent being developed for the treatment of schizophrenia and bipolar
disorder, were examined using chronic mild stress (CMS)-induced anhedonia and an intracranial self-stimulation (ICSS) protocol.
Method: In the CMS protocol, male Wistar rats were divided into stress
(eg, food/water deprivation, cage tilt, intermittent illumination) and control groups. Rats in each group were assigned to intraperitoneal treatment with asenapine 0.06, 0.2, or 0.6 mg/kg twice daily; imipramine
10 mg/kg once daily; or vehicle for 7 weeks (n=8 per group). Decreased
consumption of a 1% sucrose solution was used as a marker of anhedonia. In the ICSS protocol, male Sprague-Dawley rats were trained to press
a lever triggering an electrical stimulus to the ventral tegmental area. A
variable interval 3-second schedule was used during extinction/reacquisition and rate frequency training. An ascending rate frequency protocol
(11 conditions, 10-175 Hz, 2 minutes each) was used. From the rate-frequency curves, the locus of rise (LOR) and maximal rate of responding
(MAX) were calculated. Thirty minutes before testing, rats received subcutaneous doses of asenapine 0.01, 0.03, 0.1, or 0.3 mg/kg; cocaine
5.0 mg/kg as a positive control; or vehicle (n=7-8 per group).
Results: In the CMS model of anhedonia, both asenapine and imipramine
restored sucrose consumption to control levels (P<0.001) (from week
3 onward for asenapine 0.6 mg/kg; from week 4 for imipramine). In the
ICSS protocol, asenapine 0.1 and 0.3 mg/kg significantly increased LOR
(by 5% and 9% from baseline, respectively), and asenapine 0.3 mg/kg
significantly decreased MAX (by 59% from baseline). In contrast, cocaine
5.0 mg/kg decreased LOR and left MAX unchanged.
Conclusion: Asenapine was as effective as imipramine in decreasing
CMS-induced anhedonia, and the ICSS data suggest that this effect was
not due to an hedonic profile. These findings support the therapeutic utility of asenapine in bipolar and other affective disorders.
P-22-07
Cognitive functioning in bipolar disorders: Subtypes looking impact of premorbid IQ, obstetric complications and
psychotropic drugs
Sergio Strejilevich
AREA, Buenos Aires, Argentina
Diego Martino, Eliana Marengo, Ana Igoa, Lila Perinot, Maria Scapola,
Ezequiel Ais
Introduction: Background: Cognitive impairments have been associated
with functional outcome in patients with bipolar disorder (BD). However,
while functional outcome is very heterogeneous, nowadays it is not clear
if cognitive impairments are also heterogeneous and which are the variables that determinate it. Objectives: To examine the relationship
between cognitive impairments and exposition to psychotropic drugs,
obstetric complications history, and clinical and functional variables in
patients with BD.
Method: Forty patients with BD type I or II and twenty healthy controls
matched by age and educational level were included. In addition to SCID,
YMRS, HDRS, and GAF, clinical evaluation included measures of exposition to psychotropic drugs and obstetric complications history. All subjects
completed an extensive neuropsychological battery selected to asses premorbid IQ, verbal memory, attention, psychomotor speed, language,
executive functions, and facial emotion recognition.
Results: No differences in clinical and cognitive measures were found
between patients with BDI and BDII. Patients with BD taken as a whole
had lower performance than healthy controls in psychomotor speed,
verbal memory and executive functions that were associated with GAF
scores. However, while 37% had impairments in 1-2 and 19% in 3 or
more cognitive domains, 44% had not deficits in any cognitive domain.
BD patients with cognitive impairments had lower GAF scores and premorbid IQ than those that did not have cognitive impairments. Obstetric
complications history and years of exposition to antipsychotic drugs were
associated with impairments in psychomotor speed and executive functions measures.
Conclusion: Cognitive impairments could not be homogeneous among
BD patients. A subgroup of patients with BD could present cognitive
impairments associated with psychosocial functioning that could be independent of clinical subtype (BDI vs. BDII). BD patients with low premorbid
IQ, obstetric complications history, and high exposition to antipsychotic
drugs could represent a subgroup with lower cognitive performance and
functional outcome.
101
P-22-08
Patients and psychiatrists perspective about side effects
in pharmacological treatment in bipolar disorders
Sergio Strejilevich
Maria Scapola, Diego Martino, Ana Igoa, Eliana Marengo, Maria Calvo
Introduction: Background: Patients perspective of their pharmacological
treatments side effects has been strongly related to adherence and long
term evolution in many diseases with chronic pharmacological treatments. However, there are not previous studies about this critical issue in
people under treatment with bipolar disorder. Objective: The aim of this
study was to estimate the rate of side effects and its subjective impact
reported by outpatients with euthymic bipolar disorder and their psychiatrists, as well as to estimate the association of these variables with treatment adherence and intention of dropping out.
Method: Sixty patients with euthymic bipolar disorder in naturalistic conditions of treatment were included, and completed a modified version of
the Udvalg for Kliniske Unders/-Egelser (UKU) that estimated presence,
intensity, trouble and interference in daily life activities of side effects, as
well as adherence to treatment and intention of dropping out through
visual analogical scales. Psychiatrists completed the same scale blindly.
Results: Patients with BD reported more quantity and intensity of side
effects than those reported by their psychiatrists. The presence/intensity
of side effects was not necessarily associated with the subjective impact
(trouble and interference in daily life activities) of them. Cognitive side
effects, as memory and disatenttion complaints, could have a strong subjective impact. Quantity and intensity of side effects were not associated
with adherence to treatment. There was a negative correlation between
subjective impact and adherence to treatment.
Conclusion: Psychiatrists could underestimate the record and intensity of
side effects in their patients. Trouble ant interference in daily life activities
could be better predictors of adherence to treatment than quantity and
intensity of side effects. However, subjective impact of side effects could
explain a relatively low proportion of variance of treatment adherence
and intention of dropping out.
P-22-09
Cognitive and motor features in geriatric bipolar disorders
Sergio Strejilevich
Diego Martino, Ana Igoa, Eliana Marengo, Maria Scapola, Lila Perinot,
Ezequiel Ais
Introduction: Background: Elderly people with bipolar disorder will be
one third of the population affected by this disorder in a few years.
Although it has been mentioned that it could be an increase of neurodegenerative evolution among these people, data regarding cognitive function are very scarce. Objectives: The aim of this study was to examine the
cognitive profile in old patients with euthymic bipolar disorder and its
relationship with clinical and functional variables.
Method: Twenty patients with euthymic bipolar disorder older than 60
years old, as well as twenty healthy controls matched by age and educational level were included. In addition to Structured Clinical Interview for
DSM-IV, Young Mania Rating Scale, Hamilton Depression Rating Scale,
and General Assessment Functioning, clinical evaluation included measures of exposition to psychotropic drugs and UPDRS as a measure of
extrapiramidal symptoms. All subjects completed an extensive neuropsychological battery selected to asses IQ, verbal memory, attention, psychomotor speed, language, executive functions, and facial emotion recognition.
Results: Patients with bipolar disorder had more extrapiramidal symptoms and worse performance than healthy controls in psychomotor
speed, verbal memory, executive functions and recognition of emotions
even after controlling sub-clinical symptomatology. These findings are
not associated with age at onset or length of illness either with current
pharmacological exposition. Psychosocial functioning was negatively correlated with performance in psychomotor speed, attention and executive
functions, and correlation was almost significant with extrapiramidal
symptoms.
102
Conclusion: Old patients with euthymic bipolar disorder could have a

similar cognitive profile than the one that was reported in younger
euthymic bipolar patients. These data suggest that cognitive impairments
could not be more severe in this population. Likewise, extrapiramidal
symptoms and cognitive impairments could be better predictors of psychosocial functioning than traditional clinical variables among old bipolar
euthymic patients with bipolar disorder.
P-22-10
Quetiapine dosage in bipolar disorder episodes, a retrospective chart review
Yasser Khazaal
CHUV, Dept. of Psychiatry, Lausanne, Switzerland
Anne Chatton
Introduction: Although the maximal quetiapine doses in the published
studies were restricted to 800mg/day, higher quetiapine doses are not
unusual in clinical practice. The aim of the present study was to evaluate,
effectiveness, tolerability and clinical reasons associated to the use of high
dosage of quetiapine (> 800 mg), when used under routine clinical conditions, in a sample of bipolar disorder and schizoaffective bipolar inpatients
Method: Charts of all bipolar and schizoaffective adult inpatients, who
had received quetiapine for a mood episode between 1999 and 2005
were retrospectively reviewed. These charts also included the assessment
of manic and depressive symptoms on admission and at discharge using
the Bech-Rafaelsen Mania Scale (MAS)(1) and the Montgomery Asberg
depression rating scale (MADRS)(2), respectively.
Results: Ninety fourth charts were analyzed. The repeated measures
ANOVA revealed a significant MAS scores reduction between admission
and discharge (F=171.4, p< 0.0005). MAS scores reduction did not differ
between the high and low quetiapine groups (p=0.9). Similarly, a significant MADRS reduction was found (F=156.2, p<0.0005). Again, no differences between the high and the low dose group was found (p=0.7).
Moreover, a logistic regression analysis revealed that female sex (p=0.01),
MAS score at admission (p=0.005) and mixed episodes (p=0.001) predicted high quetiapine dosage.
Conclusion: The present study confirms quetiapine efficiency and tolerability in the treatment of bipolar episodes, even in doses > to 800 mg and
found a link between mixed episodes, severity of manic symptoms and
quetiapine doses.
References: 1.Bech P. The Bech-Rafaelsen Mania Scale in clinical trials of
therapies for bipolar disorder: a 20-year review of its use as an outcome
measure. CNS.Drugs 2002; 16:47-63. 2.Montgomery SA, Asberg M. A
new depression scale designed to be sensitive to change. Br.J Psychiatry
1979; 134:382-9
P-22-11
Lamotrigine and recurrent depressive disorder
Eugenio Chinea
Hospt Univ. de Canarias, Servicio de Psiquiatria, La Laguna, Spain
M. Henry, R. Gracia
Introduction: Studying the effectiveness of lamotrigine as a strengthening drug in refractory depression.
Methods: Lamotrigine was added, and increased up to 100-150 mg/day,
to 7 adult outpatients with resistant depression. The previous antidepressant dose was not changed at all. Bipolar disoder patients were excluded.The short version of Becks Depression Inventory (BDI) and the Clinical
General Impression scale (CGI) was applied to each patient at the beginning and after 6 weeks of treatment. Sociodemographic data, age of
onset, duration of the current depressive episode, previous antidepressants, simultaneous psychotherapy, comorbidity and side effects were collected and registered. Statistical analysis was carried out.
Results: All female patients, mean age 44, 13 years from onset. Most frequent diagnosis, recurrent depressive disorder. Duration of present episode, 5 months. All the patients suffer from resistant depression with a previous bad response to different antidepressants. Wilcoxon-signed-rank
test showed that CGI score decreased from 5 to 2 (p=.0313) and BDI
score from 24 to 16 (p=.0625). No significant side effects were observed
Conclusion: Depressive symptoms have considerably improved by adding

lamotrigine to antidepressant treatment. Bigger samples, during more
lengthy periods and control groups are needed in order to assess the real
strengthening role of lamotrigine in depression.
P-22-12
Treatment characteristics according to clinical stability in
bipolar patients
Pedro Retamal
Universidad de Chile, Psiquiatria y Salud Mental, Santiago, Chile
Juan Carlos Almonte, Claudio Fullerton, Yamil Quevedo
Introduction: The clinical stability of bipolar patients is a great challenge
to find the best psychopharmacological intervention. This study present
data about clinical stability and different treatments in a group of bipolar
patients treated at Mood Disorder Clinic of Hospital del Salvador,
Santiago de Chile, between 2004-2005. To compare the use of different
medications (antidepressants, antipsychotics, lithium, benzodiacepines
and polypharmacy) in stable and unstable patients.
Method: The scores of HAM- D-7, CGI-BP-M and Analogic Visual Scale
and information about hospitalization, suicidal ideation/intents, use of
antidepressants, antipsychotics, lithium and benzodiacepines were obtain
from 65 file records. Polypharmacy was defined as concomitant use of
4 o more drugs. Stable and unstable groups of patients were defined.
Unstable patients: with hospitalizations, suicide ideation/intent and/or
HAM-D 7 and/or CGI-BP-M scores above threshold. Chi-square test were
use for statistical analysis.
Results: 90% of patients were female (n=50), mean age= 50 years old.
68% were stable patients. The unstable group of patients (n=21) used
more frequently antipsychotics (62% vs. 30%, p=0,015); antidepressants
(62% vs. 18,6%, p=0,001); anticonvulsants (90,5% vs. 61,4%, p=0,016)
and polypharmacy (43% vs. 4,7%, p<0,001). No differences were found
in the use of Lithium and Thyroid hormone.
Conclusion: There were statistical difference between the treatments
indicated to stable and unstable bipolar patients. Unstable patients
received significantly more pharmacological interventions and polypharmacy.
P-22-13
Treatment of a patient with bipolar affective disorder
and Sneddons Syndrome by administration of cyclophosphamide: A case report
Andreas Stravogiannis
Sao Paulo, Brazil
Andre Castilho Valim, Breno Oliveira Diniz, Ana Patricia Nascimento,
Mauricio Levy Neto, Teng Chei Tung, Doris Hupfeld Moreno, Frederico
Navas Demetrio
Introduction: Sneddons Syndrome is a rare vasculitis, which has an estimated incidence of 4 cases/million and represents approximately 0.26%
of all causes of cerebrovascular disease. It is recognized by the association
of cutaneous livedo racemoso and multiple cerebral infarctions, most
commonly affecting women aged between 20 and 42 years. Little more
than 140 cases are reported in the literature. Psychiatric manifestations
may develop due to cerebrovascular lesions; there is one case reported in
which remission of psychotic symptoms was made possible after intravenous administration of cyclophosphamide and oral prednisolone.
Method: We report the case of CMTM, female, 50 years old, diagnosed
with both Sneddons Syndrome and Bipolar Affective Disorder. She had
already presented 2 isquemic strokes, without severe neurological deficits.
After 18 psychiatric inpatient treatments and electroconvulsive therapy,
she had only shown parcial and transitory symptomatological improvement. A brain magnetic resonance imaging revealed a right parieto-occipital lesion, and laboratory findings showed discrete inflammatory activity.
Results: During inpatient stay due to a current episode of severe depression with psychotic symptoms, she underwent 3 cycles of intravenous
cyclophosphamide, presenting afterwards complete symptomatologic
remission, the first one in over 25 years.
Conclusion: This patients evolution shows that in psychiatric cases
refractory to convencional treatment and with documented clinical
comorbidity, the choice of treating the latest should be considered, even
when its presentation shows to be subclinical.
References: Bolayir et al: Sneddons Syndrome:Clinical and Laboratory
Analysis of 10 Cases. Acta Med Okayama 2004 58(2): 59-65. Kume M

et al: Sneddons Syndrome (Livedo Racemosa and Cerebral Infarction)
Presenting Psychiatric Disturbance and Shortening of Fingers and Toes.
Intern Med 1996 35(8): 668-73. Weissenborn K et al: Neuropsychological
deficits in patients with Sneddons syndrome. J Neurol 1996; 243(4): 35763. Wohlrab J et al: Strange symptoms in Sneddons syndrome. Cl Immun
2006 119(1): 13-15.
P-22-14
Lithium as a protective factor for cognitive decline in elderly patients with bipolar disorder
Stevin Zung
University of Sao Paulo, School of Medicine, Brazil
Quirino Cordeiro, Homero Vallada
Introduction: Lithium became over the past five decades the most used
drug for the treatment of bipolar disorder (BD), but only recently its
molecular mechanism of action is being better understood. Recent studies have identified new targets of lithiums action, probably responsible
for a neurotrophic and neuroprotective effect of this drug. The effects of
the chronic lithium treatment in the cognitive function of elderly bipolar
patients in unknown. We compared cognitive function among elderly
bipolar patient using lithium and those not using lithium chronically.
Method: Patients with bipolar disorder, aged 60 years and older, were
recruited from two university psychiatric hospitals of Sao Paulo, Brazil.
Demographic and clinical characteristics of BD were obtained from medical records and from interviews with the patients and relatives. To asses
the cognitive function, the Informant Questionnaire on Cognitive Decline
in the Elderly (IQCODE) were used. The scores of IQCODE were compared
between the patients using and those not using lithium.
Results: A hundred and thirty five individuals enrolled in the study, with
a mean age of 68.7 years. The cognitive evaluation was done in one hundred and twenty two patients. Fifty four percent of the patients were
using lithium. Patients taking lithium had lower cognitive decline
(IQCODE=3.09) than those not taking lithium (IQCODE=3.33) (p=0.002).
Conclusion: These results may reflect the potential neuroprotective
effects of lithium, and bring us new perspectives on the clinical use of this
mood stabilizer in Alzheimers disease and other neurodegenerative diseases.
References: 1- JORM AF, JACOMB PA. The Informant Questionnaire on
Cognitive Decline in the Elderly (IQCODE): socio-demographic correlates,
reliability, validity and some norms. Psychol Med. 1989;19:1015-1022. 2HUANG X, WU DY, CHEN G, MANJI H, CHEN DF. Support of retinal ganglion cell survival and axon regeneration by lithium through a Bcl-2dependent mechanism. Invest Ophthalmol Vis Sci. 2003; 44: 34754. 3HIROI T, WEI H, HOUGH C, LEEDS P, CHUANG DM. Protracted lithium
treatment protects against the ER stress elicited by thapsigargin in rat
PC12 cells: roles of intracellular calcium, GRP78 and Bcl-2.
Pharmacogenomics J. 2005; 5: 10211. 4- JORDA EG, VERDAGUER E,
CANUDAS AM, JIMNEZ A, GARCIA DE ARRIBA S, ALLGAIER C, et al.
Implication of cyclin-dependent kinase 5 in the neuroprotective properties
of lithium. Neuroscience. 2005; 134: 100111. 5- JOPE RS. Lithium and
GSK-3: one inhibitor, two inhibitory actions, multiple outcomes. Trends
Biochem Sci. 2003; 24: 441 43.
P-22-15
Long-term monitoring in bipolar disorder: Clinical and
pathophysiological implications
Greg Murray
Swinburne Univ. of Technology, Psychology, Hawthorn, Australia
Introduction: The present research into Bipolar Disorder (BD) has both
clinical and basic aims. Growing out of research into the instability hypothesis, the study aims to explore the possibility that changes in sleep/wake
cycles and mood can be used to predict deterioration in the wellbeing of
patients diagnosed with BD. The second aim is more directly clinical - it
was predicted that participating in a long-term monitoring study such as
the present would have beneficial clinical effects, as measured in improved wellbeing from baseline.
Methods: Fifteen participants with a confirmed diagnosis of BD I will be
enrolled into the study. Participants will be recruited from the Bendigo
Health Care Group.
Results: Preliminary analyses suggest
Conclusion: It is concluded that
103
AFFECTIVE DISORDERS (UNIPOLAR) - Poster
P-02
Affective Disorders (Unipolar)
P-02-01
Cognitive dysfunction in depression
Jitendra Trivedi
K.G.Medical University, Dept. of Psychiatry, Lucknow, India
Introduction: Cognition in a broad sense means information processing.
It denotes a relatively high level of processing of specific information
including thinking, memory, perception, motivation, skilled movements
and language. Cognitive psychology has become an important discipline
in research of a number of psychiatric disorders including depression.
Research in this area of neurocognition has started unlocking various
secrets of psychiatric disorders, like revealing the biological underpinnings, explaining the underlying psychopathology and issues related to
the course, out come and treatment strategies. The decrement in cognition has been attributed to reduced motivation, attenuated attentional
capacity, impaired concentration, intrusive thought and slowness. During
depressive episodes, patients show both quantitative and qualitative alterations in cognitive processes; these processes include learning, memory,
attention, perception, and speed of cognitive response. The cognitive
functions are also related to several crucial epidemiological variables such
as age, treatment, duration & chronicity and number of episodes.
Cognitive deficits are more pronounced in melancholic than non-melancholic depression. Significant controversies however exist regarding the
impact of severity and subtype on cognition. It is still not clearly evident
whether the cognitive deficits seen during the depressive phase represent
the state or trait characteristic. All these issues including some findings
from study carried in our own centre will be discussed in the poster presentation.
Methods: Not Applicable
Results: Not Applicable
Conclusion: Not Applicable
References: 1. Weingartner H, Cohen RM, Murphy AL, et al: Cognitive
processes in depression. Arch Gen Psychiatry 38:42-47, 19812. Cohen
RM, Weingartner H, Smallberg SA, et al: Effort and cognition in depression.
Arch Gen Psychiatry 39:593-597,1982
P-02-02
C-reactive protein (CRP) is associated with polymorphisms
of the angiotensin converting enzyme (ACE) gene in
depressed patients
Thomas C. Baghai
Ludwig-Maximilian-University, Psychiatry and Psychotherapy, Munich,
Germany
Sibylle Haefner, Daniela Eser, Cornelius Schuele, Christoph Born,
Gabriella Bedarida, Clemens von Schacky, Rainer Rupprecht, Brigitta
Bondy
Introduction: Major depressive disorder (MDD) has been associated with
cardiovascular disorders (CVD) and mortality. Inflammatory processes are
related to both disorders. CRP levels are associated with cardiovascular
risk and increased in MDD. ACE is involved in the activation of the renin
angiotensin aldosterone system (RAAS) which plays a pivotal role in the
initiation and maintenance of vascular inflammatory response. There is
evidence that variants of the ACE gene contribute to CVD and are associated with MDD and the hypothalamic-pituitary-adrenal (HPA)-axis activity. We therefore investigated CRP serum concentrations in relation to
ACE gene variants MDD.
Method: After informed consent CRP serum concentrations were determined in 70 patients suffering from MDD before treatment and in 68
healthy controls. In addition in 45 patients after 2 and 4 weeks of treatment and before discharge from hospital the measurements were repeated. All patients and controls were genotyped for ACE polymorphisms
(Ins/Del polymorphism, SNPs rs4291 and rs4295). High-sensitivity CRP
concentrations were determined with a commercially available ELISA.
104
Results: Basal CRP was significantly higher in patients than in controls.

Considering CRP levels above 2.2 mg/l as indicative for subtle inflammatory processes, 41.7% of the patients, but only 22.4% of controls had
elevated levels. Basal CRP in patients was significantly correlated with the
severity of depression (HAM-D17). The percentage of patients with elevated CRP levels increased during antidepressant treatment from 41.4%
to 60%. We found a significant relation between basal CRP and the ACE
SNPs rs4291 and rs4295, but not with the ACE Ins/Del-polymorphism.
During the treatment, all three ACE polymorphisms could be related significantly to the CRP increase, with highest values in homozygous carriers
of the ACE D-, the rs4291 T- and the rs4295 G-allele.
Conclusion: Our findings confirm the hypothesis that elevated CRP-levels in MDD and CVD may be related the same genetically determined
pathophysiologic processes within the RAAS. In addition we could not
demonstrate a reduction of CRP levels and cardiovascular risks during
antidepressant treatments.
P-02-03
The influence of age for circadian dynamic of parameters of
autonomic activity in treatment of endogenous depressions
Sergejus Andruskevicius
RVPL, Vilnius, Lithuania
Introduction: The purpose of study is to investigate the influence of age
for circadian dynamic of parameters of the spectral analysis of the heart
rate variability in treatment of depressions.
Method: 56 patients - 28 females and 28 males (mean age 46,9+1,4
years) have been studied. According to ICD-10, all of them were diagnosed to have depression (F 31.3-31.4, F 32.0- 32.2, F 33.0-33.2).
Depending on age the patients have been divided into two groups: group 1
(age 19 - 49 years, mean age 41,01,4 years) 35 patients and group 2
(age 50 - 73 years, mean age 56,61,4 years) 21 patients. In assessing
the autonomous regulation the spectral analysis of the heart rate variability was applied. The patients were examined at 1 a.m., 7 a.m., 1 p.m.,
7 p.m. The control group consisted of 15 mentally healthy people (mean
age 44,92,4 years). The group was examined at 1 a.m., 4 a.m., 7 a.m.,
9 a.m., 11 a.m., 1 p.m., 3 p.m., 4 p.m., 5 p.m., 7 p.m. in summer.
Results: The primary more pronounced features of de-synchronisation
for the middle age people were characteristic in the night and in the
morning hours, for the old aged people - in the day hours. Group 1
already at the beginning of the therapy has experienced the resynchronisation features. In the group 2 the de-synchronisation was getting
stronger during the whole day. By the discharge the resynchronisation
was more completed in the middle age group. The sympathetic impact
was more pronounced in the old aged group.
Conclusion: The investigation data show the reduction of compensation
possibilities for desynchronising circadian rhythms by aging in the treatment of depression.
P-02-04
Evaluation of the treatment in patients with severe
depression, in a psychiatric service in a public hospital of
Santiago, Chile ( SPHDS)
Ana Calderon
Hospital del Salvador, Servicio de Psiquiatria, Santiago de Chile, Chile
Ramon Florenzano, Patricia Toloza, Cristiian Zuniga, Andrea Vacarezza
Introduction: The prevalence of depression reaches 7.5% to 10% of the
adult population in Chile. As it depression has been classified as a condition GES (Explicit Guaranties in Health), each day it is more necessary to
optimize its resolution. For the treatment of depression and severe disthimia we propose to integrate pharmacological treatment with psychotherapy and other psychosocial interventions. This study shows the
results of the treatment of cases in a specialized unit of the General
Hospital of Santiago de Chile.
Method: Objective : Evaluate the evolution of the patients treated at the
Unit of Afective Disorders ( Unidad de Trastornos Afectivos UTA ) at the
SPHDS, through the OQ 45.2 and describe socialdemografically the population at this unit.Sample: 332 patients (82% women ; age X: 42 years
old) with successive measurements of OQ 45.2.Treatment: Pharma-
cological in all cases and psychological in 55%. Instrument: OQ 45.2

applied at intake and two months after treatment. Analisis : SPSS version
14.0 significance 0.05.
Results: The reasons to refer to specialized unit were : Bipolarity (38.9%) ;
Refractivity (27%) ; Suicidability (24.7%) ; Psychosis (3%) ; and Duality
(2%).The global cutpoints of the OQ 42.5 decreased from 96 at first
measurement (M1) to the third (M3). The symptoms decreased from 60
to 50 points between M1 and M3. The interpersonal problems decreased
from 20 to 17, and the social role varied only from 15.5 to 15.3, without
any significant difference in statistics. The 159 cases that had 3 measurements presented a major decrease in the global points. The attrition in
treatment was 50% between M1 and M3; this result is minor than in
ambulatory patients in SPHDS (93%).Suicidal depression and bipolarity
showed the major decrease of points followed by refractoriousness. The
dual charts varied little their points between M1 and M3.
Conclusion: This study shows the necessity to evaluate constantly the
impact of the treatments to affective disorders, specially in the Chilean
case due to massive inversion done by the GES Depresion program. The
maintenance in treatment for these patients is crucial, as also the training
of professionals in diagnosis and treatment.
P-02-05
Meningiomas and treatment - resistant depression - three
case reports
Margarida Lobo
Hospital N. Senhora do Rosario, Psychiatry, Barreiro, Portugal
Susana Fernandes, Susana Mendes, Zaida Pires, Antonio Paiva, Julieta
Chainho, Jose Graca, Manuela Pereira
Introduction: Patients with brain neoplasms usually present with focal
neurological disturbances. Nevertheless, some tumors manifest exclusively
with neurobehavioral or psychiatric features. Because the number of psychiatric patients that have brain tumors is small, it is a matter of debate
whether all patients with newly recognized psychiatric symptoms should
undergo neuroimaging studies. The authors present three cases of
patients with clinical depression, which were unresponsive to appropriate
anti-depressant medication. CT- scans of the head where then performed,
revealing meningiomas in all three.
Method: Literature review derived from the MEDLINE and PUBMED database.
Results: The authors discuss the indications of neuroradiologic evaluation
of patients with psychiatric presentations.
Conclusion: This series of cases highlights the importance of searching
for possibly curable neoplasms that might otherwise go undetected.
References: Good RS, Need for routine medical screening of psychiatric
patients. Am J Psychiatry. 1991 Mar;148(3):400; Moise D, Madhusoodanan S. Psychiatric symptoms associated with brain tumors: a clinical
enigma. CNS Spectr. 2006 Jan;11(1):28-31. ; Mainio A, Hakko H, Niemela
A, Koivukangas J, Rasanen P. Depression and functional outcome in
patients with brain tumors: a population-based 1-year follow-up study. J
Neurosurg. 2005 Nov;103(5):841-7. ; Madhusoodanan S, Danan D,
Brenner R, Bogunovic O. Brain tumor and psychiatric manifestations: a
case report and brief review. Ann Clin Psychiatry. 2004 AprJun;16(2):111-3. ; Wellisch DK, Kaleita TA, Freeman D, Cloughesy T,
Goldman J. Predicting major depression in brain tumor patients.
Psychooncology. 2002 May-Jun;11(3):230-8. ; Pringle AM, Taylor R,
Whittle IR. Anxiety and depression in patients with an intracranial neoplasm before and after tumour surgery. Br J Neurosurg. 1999
Feb;13(1):46-51.; Schwenk TL. Cancer and depression. Prim Care. 1998
Jun;25(2):505-13.; Filley CM, Kleinschmidt-DeMasters BK. Neurobehavioral presentations of brain neoplasms. West J Med. 1995
Jul;163(1):19-25; Good RS. Need for routine medical screening of psychiatric patients. Am J Psychiatry. 1991 Mar;148(3):400; Fornes L, Arboix A,
Rodriguez E, Torres M. Psychiatric manifestations as the presenting form
of primary cerebral tumor. Rev Clin Esp. 1990 Mar;186(4):194-5.; Galasko
D, Kwo-On-Yuen PF, Thal L. Intracranial mass lesions associated with lateonset psychosis and depression. Psychiatr Clin North Am. 1988
Mar;11(1):151-66.
P-02-06
Survey of exercise effect on mild postpartum depression in
women in ardabil health centers
Afrouz Mardi
Medical University, Health, Ardebil, Iran
Introduction: Background & Objective: Postpartum depression is a problematic and destructive disease and if dont be recognize and treatment,
it will be aggravate or longing. Exercise is the one of the efforts to advise
to prevent of any disorders in companionship and securing of mother,
child and family health. Aim of this study was appointment of exercise
effect on postpartum mild depression in women in Ardabil Health centers.
Methods: This study was a double blind clinical trial. About 50 subject
with natural delivery at second week of postpartum that had mild depression with Beck scale, selected randomly in two groups (exercise and nonexercise). Then Beck test was done 6 weeks after delivery again. And
results were compared in two groups.
Results: The findings indicated that between mild depressed women,
36% had 26-30 years old, 82%were housekeeper, 44% had under diploma education, 60%had two previous of delivery and 32% of non-exercise group had well-being, and 8% Versus 18% needed to psychologist
counseling at 6 weeks after delivery. Qui-square test showed significant
differences between two groups (p<0.05).
Conclusion: Results showed that exercise had a positive effect on the
well-being of postpartum mild depression.
P-02-07
The Integral Inventory for Depression (IID), a new clinimetric tool for the emotional and physically painful
dimensions of depression
Hector Duenas
Eli Lilly, Mexico, Neurosciences, Mexico City, Mexico
Guillermo Tapia, Juan Luis Vazquez, Adriana Acuna, Eduardo Madrigal,
Omar Kawas, Antonio Celis, Adrian Vargas, Maria del Carmen Lara
Introduction: IID has been validated for detecting and evaluating severity
of both the emotional (ED) and the physically painful (PPD) dimensions of
Major Depressive Disorder (MDD).
Method: 121 patients with MDD as per DSM-IV TR and 88 patients
attending psychiatric consultation but not depressed after signing their
ICD answered the IID and the SCL-90 before their consultation. Then the
Investigators evaluated his/her patients and rated with the IID and the
HAMD-17 only to those that presented with symptoms of MDD.
1) Internal Consistency was calculated with Cronbachs Alfa Test to the
patients and Investigators scoring of the IID; 2) External Consistency was
calculated with the intraclass Pearsons correlation coefficient,
3) Convergent Validity was calculated with Pearsons correlation coefficient and 4) Construct Validity with the differences among groups in the
SCL-90: depressed and non-depressed.
Results: 1)For the patients ED was 0.86 and Investigators 0.82, for the
patients PPD was 0.82 and Investigators 0.79; 2)Correlation coefficient
between the patients and Investigators scorings were 0.88 for ED and
0.9 for PPD. 3)Correlation between HAMD-17 and IID was -0.35 for the
ED and -0.21 for the PPD; for the item 13, -0.16 for the ED and -0.30 for
the PPD. Between the SCL-90 and IID in ED, -0.77 and -0.60 for the PPD.
4)For the non-depressed patients the mean scoring in ED was 19.6 5.03,
in PPD 35.43 4.7 and in total score 55.03 8.53; whilst the Investigators
was correspondently 22 2.16; 40.25 2.21 and 62.25 2.21. For the
depressed patients the means in ED were 12.86 4.51, in PPD 29.95
5.34 and in total score 42.81 8.11; whilst the Investigators were correspondently 11.71 3.95, 29.75 5.36, and 41.47 7.44 with a consistent significative difference among all means in both groups of p=0.0001.
Conclusion: IID is a valid and reliable tool for detecting and evaluating
severity in both the ED and the PPD of MDD.
105
P-02-08
Male depression and testosterone
Urban Groleger
Univ. Psychiatric Hospital, Ljubljana, Slovenia
Katarina Barbara Strukelj
Introduction: Under-recognition of depression is associated both with
male sex, middle age and atypical clinical presentations. Atypicality is
among other factors associated with hormonal imbalance and aging in
male. Andropause is clinically presented with similar symptoms then
depression, both co-occuring more often, that this could be attributed to
chance.
Method: Males, aged 20 to 49 and 50 to 80 with clinically diagnosable
depression according to ICD-10 and HAM-D, have been tested for testosterone levels, prolactine and other metabolic variables. According to
testosterone levels, males with low and normal values were compared
accordinh to symptome dimensions of depression.
Results: Preliminary results at the time of abstract submission show, that
testosterone levels differentiate bewteen typical and atypical clinical
symptoms of depression and influence response to antidepressant treatment.
Conclusion: Testosterone levels influence clinical presentation in males
with depression. When hypogonadism is not recognized, the response to
treatment and course of depression are worse then in testosterone normal depressed males.
References: 1. Carnahan RM, Perry PJ. Depression in aging men: the role
of testosterone. Drugs Aging. 2004; 21(6): 361-76. 2. Araujo AB,
ODonnell AB, Brambilla DJ, et al. Prevalence and incidence of androgen
deficiency in middle aged and older men: estimates from the Massachusetts
male aging study. J Clin Endocrinol Metab 2004; 89: 592-6.
P-02-09
Association study of serotonergic genes and Major
Depressive Disorder (MDD)
Luisa Herrera
University of Chile, Human Genetic, Santiago, Chile
Guillermo Lay-Son, Claudio Zamorano, Paulo Pereira, Carlos Moya,
Jenny Fiedler, Graciela Rojas, Paulina Rojas, Romina Rojas, Rosemarie
Fritz, Rosemarie Fritsch
Introduction: Substantial evidence suggest that dysfunction of brain
serotonergic system is involved in the pathogenesis of many complex psychiatric diseases (PD). Accordingly, genes involved in serotonin neurotransmission are strong candidates for a role in the genetic etiology of
affective illness. The goal of this study is to carry out association studies
between major depressive disorder (MDD) with polymorphisms in candidate genes, including two VNTR in the Serotonin transporter (5-HTT)
gene, HTTLPR and Stin2, and one in the serotonin receptor 1B (5HT1B)
gene. Association studies with MDD at these loci have not been studied
in Chilean patients.
Method: 52 patients and 31 controls were recruited for this study. HTTLPR and Stin2 were genotyped using PCR, and 5HT1B*G861C by PCRRFLP digesting with the enzyme Hinc II. HardyWeinberg equilibrium was
tested using the Chi2. Odds ratio (OR) and its confidence interval (CI)
were calculated using Epi Info version 6 package. Differences in the distribution of genotypes of two or three loci, between patients and controls, were analyzed using montecarloss simulation (RxC program), based
on the Roff y Bentzen (1989) algorithm, and 10000 replications of permutations of alleles.
Results: Patients and control groups were in Hardy-Weinberg equilibrium.
No significant differences between patients and controls were found for
HTTLPR or 5HT1B*G816C. A significant association between MDD with the
Stin2*10 allele was found (OR 2.73 CI 0.97-7.79). Interestingly, we also
found two genotypes significantly overrepresented in the control group.
They are HTTLPR SL - Stin2*12/12 - 5HT1B861GG with a p value of 0.021
and HTTLPR SL - VNTR LL with an even more significant p value of 0.0074.
Conclusion: These results suggest that the 10 repeats allele of Stin2 is a
risk factor to develop MDD, and on the other side the genotypes SERTPRSL Stin2*12/12 5HT1B861GG, and HTTLPR SL Stin2*12/12 exhibit protective effects. Universidad de Chile. DI 336
106
P-02-10
Cortisol, CD19 and CD56 cell in patients with major depressive disorder
Sang Ick Han
Our Lady of Mercy Hospital, Psychiatry, Incheon, Korea, Republic of
E. Jin Park, Yang Whan Jeon
Introduction: In depressive illness, a wide variety of disturbances in
endocrine systems and immunologic parameters have been reported. In
this study, to investigate the relationship among the endocrine, immune
system and clinical symptoms in patients with unmedicated major depressive disorder (MDD) in acute state, we measured the clinical symptom and
plasma ACTH, cortisol and peripheral lymphocyte parameters were examined.
Method: 44 patients with MDD from outpatient clinic were recruited. To
investigate depressive symptom, we administered Hamilton Depression
Rating Scale (HDRS) for the subjects. 17-items of HDRS were factorized
using the confirmatory factor analysis and three factors were obtained:
depression factor (Fd), anxiety factor (Fa), insomnia factor (Fi). Plasma
ACTH, cortisol and peripheral lymphocyte or NK cell measures (CD3, CD4,
CD8, CD 19 or CD56) was obtained. We calculated Pearsons correlation
coefficients and used the STATISTICA program for statistical analyses.
Results: There was a significant negative correlation between Fd and
CD56 cell number (r = -0.31, P < 0.05). There was a significant positive
correlation between Fa and CD19 (B) cell number (r = 0.45, P < 0.01) and
between Fi and cortisol level (r = 0.33, P < 0.05).
Conclusion: Number of CD 56 (NK T) cells was negatively correlated with
depression factor. Decreased CD 56 cells in acute, major depressed
patients may reflect the core symptoms in acute major depression and
suggest the possible involvement of an immune suppression in depression.
Also our data showed influences of anxiety factor on CD 19 (B) cell distribution and influences insomnia factor on cortisol level in major depression
in acute state. In this study, endocrinological and immunological change
in patients with major depressive disorder may reflect various factors of
depression respectively.
References: Seidel, A., Arolt, V., Hunstiger, M., Rink, L., Behnisch, A.,
Kirchner, H., 1996. Increased CD56+ natural killer cells and related
cytokines in major depression. Clinical Immunology and Immunopathology 78, 83-85. Ravindran, A.V., Griffiths, J., Merali, Z., Anisman,
H., 1998. Circulating lymphocyte subsets in major depression and dysthymia with typical or atypical features. Psychosomatic Medicine 60, 283-289.
P-02-11
Exploring the link between gender and depressive and
post-stress disorders in psychiatric and non-psychiatric
medical centers
Samvel Sukiasyan
Center, Yerevan, Armenia
Samvel Margaryan, Narine Manasyan, Arpine Kirakosyan, Anna
Babakhanyan, Marine Ordyan, Ashkhen Pogosyan
Introduction: The gender factor is one of the considerable factors in the
formation of depressive and post-stress disorders. The main objective of
this study is to find out gender differences between inpatients of a psychiatric hospital and outpatients of multidisciplinary diagnostic center as
indicators to reveal the rate of depressive and post-stress disorders, in
order to perform appropriate models of organization of specialized help
in primary health care settings.
Method: We work out appropriate documents to collect the clinical and
epidemiological data. The research package includes the following documents: the clinical-epidemiological questionnaire, somatisation mental
disorders revealing questionnaire, the Toronto scale of alexitimia, the scale
of depression Montgomeri-Asberg (MADRS), the scale of anxiety of
Spillberger. The mental disorders diagnosed according to ICD-10. There
were investigated 148 patients at the Center Stress and 122 Medical
Center Diagnostica (Yerevan, Armenia). The first group we conditionally
named psychiatric, and the second one diagnostic. Baseline data
on diagnosis, symptomatology and other independent variables was collected.
Results: It was carrying out the analyses of the clinical data by gender
aspect. According to the Statistical Annual of Armenia (2006), 48.3 % of
the population of Armenia were men and 51.7 % - women. Among
psychiatric patients men were 51.4 %, women 48.6 %. Men, vice
versa, were 29.5 %, women 70.5 % among diagnostic. Thus, the
number of men was 1.07 times more among psychiatric patients, but
the number of women was 2.4 times more among diagnostic patients.
Women are underrepresented among psychiatric inpatients, because
their admission carries greater stigma and reduce their marriage
prospects. It is remarkable, that more quantity of men before had hospitalized into psychiatric and somatic hospitals. The worst mental health is
noted in single men, divorced or widowed women. It was found out from
the records of experimental-psychological investigations that the somatic
component of the state more expressed among women. There were not
revealed significant differences between the genders by heredity, premorbid personality and suicidality.
Conclusion: The detected difference between men and women in different medical centers allows concluding about the role of gender in the formation of depressive and post-tress disorders, revealing of which in primary care settings are of great importance.
P-02-12
Positive correlation between anxiety severity and plasma
levels of dheas in medication-free patients experiencing a
major episode of depression
Cheng-Cheng Hsiao
Chang Gung University, Department of Psychiatry, Keelung, Taiwan
Introduction: This study attempted to determine whether a correlation
exists between depression severity and anxiety severity and serum dehydroepiandrosterone sulfate (DHEAS) concentrations in medication-free
patients experiencing a major depression episode.
Methods: Twenty-eight medication-free major depressive outpatients
(Hamilton Rating Scale for Depression 17, HAM-D 17 score_ 17) were
enrolled consecutively. Depression severity was assessed with the HAM-D
17 and the Hospital Anxiety and Depression Scale (HADS) depression subscale. Anxiety was assessed using the HADS anxiety sub-scale. Serum concentrations of DHEAS were measured immediately following the HAM-D
17 and HADS assessments for all subjects. Continuous variables were
compared with the Student's t-test or paired-samples t-test and correlated utilizing partial correlation. Categorical variables were compared with
the Chi-square test. A two-tailed value of p < 0.05 was considered statistically significant.
Results: A significant, positive correlation was identified between HADS
anxiety sub-scale total score and morning serum DHEAS concentration
(p=0.013) after controlling for age, gender and body mass index (BMI).
Conclusion: This preliminary study provides a pilot data that morning
serum DHEA-S concentrations were positively correlated with HADS
anxiety sub-scale score (anxiety severity) after controlling for age, gender
and BMI in medication-free outpatients experiencing a major depression
episode. It is not known if morning serum DHEA-S levels would show
similar or dissimilar changes in non-depressed subjects. The result needs
subsequent replication.
References: 1.CHENG-CHENG HSIAO: Difference in pre- and post-treatment plasma DHEA levels were significantly and positively correlated with
difference in pre- and post-treatment Hamilton depression scores.
Psychoneuroendocrinology 2006; 31(7): 839-846. 2.CHENG-CHENG
HSIAO, CHIA-YIH LIU, MEI-CHUN HSIAO: No correlation of depression
and anxiety to plasma estrogen and progesterone level in patients with
premenstrual dysphoric disorder. Psychiatry and Clinical Neurosciences
2004; 58(6): 601-607. 3.Dubrovsky BO. Steroids, neuroactive steroids and
neurosteroids in psychopathology. Prog. Neuropsychopharmacol. Biol.
Psychiatry. 2005; 29:169-92.
P-02-13
Circadian and circannual serotonin rhythm in healthy
humans
Armando Morera
University of La Laguna, Psychiatry, Spain
P. Abreu, M. Henry, A. Garcia-Hernandez, F. Guillen-Pino
Introduction: The objective of this research is to study whether there is
a circannual and a circadian Serotonin (SER) rhythm of secretion.
Methods: The sample was comprised by 5 non-smoker, drug-free, healthy
male participants. None of them had a history of medical, neurological or
psychiatric disease and routine laboratory parameters were normal. The
study was carried out in accordance with the Helsinki Declaration and all
subjects gave written informed consent before their inclusion. The protocol study was approved by the University of La Laguna Committee of
Ethics and Research. Exclusion criteria were: sleep problems, abnormal
results in the metabolic or urine tests and doing shift work. Subjects were
asked to refrain from using sun glasses, drinking coffee, tea or alcohol
containing beverages 12 hours before and during the duration of the
experiment. Blood samples were extracted at 22:00, 23:00, 24:00, 01:00,
02:00 and 12:00 hours. The same routine was followed during the two
experimental sessions, in august and december. Serum SER was determined by ELISA methods, using commercial kits purchased from Immuno
Biological Laboratories. Mean nocturnal SER values, the mean of all
nocturnal values, was calculated according a five hour sample period
(22:00-02:00 hours).
Results: Next table shows the comparison of nocturnal and diurnal SER
levels in summer and winter. P levels in bold are calculated, assuming a
hypothetical sample of 10 subjects, with the same mean and standard
error of the mean. Mean nocturnal and diurnal SER levels were higher in
winter than summer. Comparison of mean nocturnal SER values with
noon serotonin value showed that in summer mean nocturnal SER level
was higher than noon SER level. In winter, there was no difference between the mean nocturnal SER level and the noon SER level. Table:
MNSER: Mean Nocturnal Serotonin level, NSER: Noon Serotonin level
TimeSummerWinterP (N=5)P (N=10) MNSER 134.4 12.7162.3
20.20.200.04 NSER 123.9 12.1168.6 23.20.090.01P (N=5) 0.130.53
P (N=10)0.020.45
Conclusion: SER has a circannual rhythm of secretion with higher nocturnal and diurnal levels in winter than summer. SER has a circadian rhythm
of secretion, higher at night than at noon, in summer. This circadian
rhythm was absent in winter.
P-02-14
Depression in Portugal: Characterizing the diagnosis and
treatment of depression by the Portuguese physicians.
Results from a survey
Mariana Guerreiro Anastacio
Lilly Portugal - Produtos Farm, Alges, Portugal
Joao Pereira, Carlos Trabulo, Luis Laranjeira
Introduction: In depression there is a range of depressive symptoms
which are relevant. This can influence the criteria for diagnosis, relapse
and remission. Physical symptoms (PSx), are very often part of depression
but are not always recognized. This can affect the treatment of depression
especially if the PSx are not spontaneously self-reported by the patients.
The intent of this survey was to understand the Portuguese physicians
level of knowledge regarding depression, especially the prevalence and
relevance of PSx.
Method: The face-to-face interviews were conducted between April 10
and June 2, 2006 in Portugal with a total of 250 physicians who are
actively practicing as either a general practitioner or a psychiatrist. All
data collected was coded and analyzed by univariated methodology in
order to establish the relative weight of each predictor. Bivariated analyses were applied, when needed.
Results: An average of 22,8% of the patients treated/week suffer from
depression. From those 80,5% had a pre-existing diagnosis and 19,5%
were new cases. Depression is more prevalent at the age of 30-50 years
(43,5%) and 69,0% were female; 73,1% suffer from depression with
anxiety, 55,7% with somatization. In 74,2% of all patients the depression
107
is mild to moderate and 60,1% had at least one relapse. 58,4% of the
physicians recognize that PSx are used to diagnose depression, but only
10% mention pain, nevertheless the most recurrent symptom to diagnose
depression is sadness (76,4%). 83,2% of physicians think that by treating emotional symptoms (ESx), they are as well treating PSx. 74,9% of
doctors believe that the patients will achieve remission if both ESx and
PPSx of depression are treated. For the treating physicians, Serotonine
and Noradrenaline Reuptake inhibitors (SNRIs) are the first choice for any
kind of depressed patient, except for patients over 50 years, where
Selective Serotonine Reuptake Inhibitors - SSRIs are the drugs of choice.
Conclusion: A large majority of the Portuguese physicians agree or
strongly agree that the failure to treat Painful Physical Symptoms (PPSx)
will increase the risk of relapse and a patient will achieve remission if both
ESx and PPSx of depression are treated. Despite all of that, the diagnosis
still relies mainly on the existence of ESx.
P-02-15
Evaluation first month, cost-effectivenes of a protocol to
treat women with severe depression and antecedents of
childhood or adolescent trauma, in public general hospital
in Chile
Veronica Vitriol
Hospital, Mental Health, Curico, Chile
Soledad Ballesteros, Ramon Florenzano, Daniel Schwartz
Introduction: The association of childhood trauma with depression has
been related to a higher cost of health services. The aim of this study is
to measure the cost-effectiveness of a protocol designed to treat in three
months the consequences of that trauma among women with severe
depression, compared to treatment as usual.
Method: :87 women with severe depression according to ICD-10 and
recollection of childhood politrauma ((69% were sexually abused), that
consulted in the Servicio de Salud Mental of the Hospital de Curico (Chile)
were randomly assigned to a treatment protocol (TP) n=44, and to treatment as usual (TC) n=43. The direct cost of each treatment was determined through a spenditure sheet according the Chilean Ministry of
Health values. It included medical, psychologist hours, days of hospitalization, medications, ambulatory and emergency clinic attendance, for each
patient during those threee months. Effectiveness was measured measuring the Reliable Change Index with the Chilean version of Lamberts
OQ45.2. Cost / effectiveness was measured as the quotient of all the
expenditures during the observation period, divided by the number of
patients recovered or improved during that time.
Results: Results First month en Chilean pesos (Ch$): Total cost of TP was
$2.946.680 Total cost of TC was $3.561. 948.The number of improved
or recovered patients was TP 19, compared to 13 in the TC. Cost-effectiveness of TP was $155.088 versus TC of $273.944. The main expenditures were in the TP cases: Psychiatric consultation 19%, medications
7%, hospitalizations 14%, psychological consultation 7%. For TC were
Hospitalization 47 %, medications 8%, psychiatric consultation 7%, psychological consultation 3%.
Conclusion: This are preliminar results, we need the results of the end of
the protocol. With this results the protocol that deals with the consequences of the trauma among women with severe depression, with
emphasis in intensive ambulatory team work, is less expensive and more
effective than treatment as usual.
References: Walker E, Katon W, et al. Helth Care Costs associated with
Postraumatic Stres disorder Symptoms in Women. Arch Gen Psychiatry
2003, 60: 369-374.
108
P-11
Affective Disorders (Unipolar) II
P-11-01
Chilean experience with SNRIs
Sergio Zamora
Servicio de Salud Mental, Psychiatry, Santiago de Chile, Chile
Introduction: Treatment with high doses of the three serotonin and
noradrenaline reuptake inhibitors (SNRI) was compared in a group of
60 patients, diagnosed with major depression according to DSM-IV criteria.
Twenty patients each were randomised to treatment with either venlafaxine (275 mg/day), duloxetine (70 mg/day) or milnacipran (100 mg/day).
Patient examinations, including Hamilton score evaluation (HAMD17) and
a sexual dysfunction questionnaire, were carried out after 1, 2, 3, 4, 6,
8 weeks and 3, 4 and 6 months.
Method: Patients (43 women and 17 men), with a mean age of 42.5
years, all had a regular sexual partner and 80% considered sexual activity
to be important. Remission rates (HAMD17 <7), 40 - 60% at 8 weeks and
63 - 88% at 16 weeks, were not significantly different between the three
SNRIs. Tolerance was generally acceptable with all three SNRIs with gastrointestinal complaints, principally nausea and gastric discomfort, being
the most common adverse effects. These were seen principally in the first
week and spontaneously disappeared thereafter. No changes in weight or
blood pressure were observed. Sexual dysfunction was present in all
patients at baseline. The principal symptoms were decreased sexual
desire, reduced frequency of sexual activity and difficulty in obtaining
orgasm. These symptoms improved with treatment with an important difference between the antidepressants (see Table). With venlafaxine and
duloxetine a large proportion of patients continued to complain of sexual
dysfunction even after 16 weeks treatment in spite of remission of most
other symptoms. Patients treated with milnacipran showed the greatest
improvement in sexual dysfunction with 95% patients reporting normal
sexual functioning at 16 weeks.
Results: % patients with sexual dysfunction Baseline 8 weeks 16 weeks
Milnacipran 100 33 5 Venlafaxine 100 80 60 Duloxetine 100 74 47
Conclusion: In conclusion all three SNRIs showed high rates of remission
of depressive symptoms with acceptable general tolerance. Milnacipran
appeared, however, to be considerably more effective in reducing sexual
dysfunction present at baseline.
P-11-02
Memantine augmentation of SSRI resisitant depression
Sermin Kesebir
Kirikkale Yuksek Ihtisas Hosp., Psychiatry, Turkey
Emine Simsek, Yasemin Simsek, Kenan Ozluk
Introduction: Recent investigations in mood disorders suggests that
NMDA receptor antagonist ketamine might demonstrate rapid antidepressant properties. Open label trials in treatment resistant depression
have yielded promising results. Likewise AMPA receptor potentiators
favorably impact neurotrophic factors as well as enhance cognition.
Objective of this study was to investigate whether the addition of
Memantine helps relieve depressive symptoms who failed to respond to
an adequate course of standard SSRI antidepressant treatments.
Method: Patients who fulfilled the DSM-IV criteria for non-psychotic
major depression and failed to show satisfactory response after a minimum of six weeks adequate treatment were recruited. Their 17 itemHAMD score had to be 18 or more. They were all started on 10 mg
Memantine and the dose was increased to 20 mg within a week when
tolerated, they continued the combination for a minimum of three weeks.
Results: 11 patients who ranged from 22-66 years of age completed the
trial. Memantine augmentation was assosiated with statistically significant drop (p<0.004) in the mean HAMD at end of three weeks compared
to baseline scores. 6 patients showed 50% or more improvement on
HAMD scores, with 3 achieving full remission.
Conclusion: Memantine augmentation resulted in improvement of mood

scores. Even though one patient withdrew prematurely due to side effects,
the remaining 11 patients tolerated the addition of memantine very well.
References: 1. Moryl E, Danysz W, Quack G. Potential antidepressive
properties of amantadin, memantine and bifemelane. Pharmacol Toxicol
1993, 72(6):394-7. 2. Parsons CG, Danysz W, Quack G. Memantine is a
clinically well tolerated NMDA antagonist. Neuropharmacology 1999,
38(6): 735-67. 3. Zarate CA, Singh JB, Quiroz JA. A double blind, placebo controlled study of memantine in the treatment of major depression.
Am J Psychiatry 2006, 163(1): 153-5.
P-11-03
Perceptive-auditory and acoustic voice analysis in patients
with major depression and remission
Andrea Lotto
IPQ HC FMUSP, GRUDA, Sao Paulo, Brazil
Maria Gabriela Cunha, Ldia Nakamura, Odeilton Tadeu Soares, Ricardo
Alberto Moreno
Introduction: Studies demonstrate that there are some specific differences between depressive patient voice parameters findings and non
depressive. The present study aimed to verify the perceptive-auditory and
acoustic evaluation in two patients with major depression, remission versus severe episode.
Method: The perceptive- auditory and acoustic measures were evaluated
in two patients with major depression, remission versus severe episode,
from Hospital das Clnicas Institute of Psychiatrys infirmary (IPq) at the
University of Sao Paulo Medical School (HC FMUSP). The patients were
received a DSMIV- TR (2000) diagnose; the following scales were applied:
HAM -D 17 (Gorenstein, 2000); VHI- Voice Handicap Index (Jacobson et
al, 1997); Vocal Profile Evaluations Protocol (Behlau, 2000); GRBAS
(HIRANO, 1981) to evaluate the dysphonia grade (G) by the identification
of four isolated parameters: (R) Roughness, (B) Breathiness, (A) Asteny
and (S) Strain; the deviations gradation is 0 (no deviation) to 3 (severe
deviation). The voices were recorded in a proper room, with lapel microphone, using the Sound Forge 6.0 version (editing software) and the
PRAAT 4.0.47 version (voice analyzer).
Results: Comparing the results between both patients, our findings
matches with the literature, the patient in depressive episode has a light
breathiness; weak loudness; melodic poorness; apathetic and fatigued
voice; GRBAS (HIRANO, 1981) findings were: G= 1 R=1 B=1 A= 0 S= 0;
and the remitted patient demonstrated an appropriate melodic voice with
G= 1 R= 1 B= 0 A=0 S=0 score.
Conclusion: Our findings suggest that voice qualities have their own
characteristics in depressive patients and can interfere in different voice
parameters, providing objective methods to help the depression evaluation.
References: Alpert M, Pouget ER, Silva RR. Reflections of depression in
acoustic measures of the patients speech. Department of Psychiatry,
Room HN 323, NYU Medical Center, 550 First Avenue, New York, NY
10016, USA. J Affect Disord. 2001 Sep;66(1):59-69. Bedard C, Belin P. A
Voice Inversion Effect. Department de Psychologie, Universite de
Montreal, C. P. 6128, succursale Centre-ville, Montreal, Quebec, Canada
H3C 3J7. Brain Cogn. 2004 Jul; 55 (2): 247-9 Behlau M, Voz. O Livro do
Especialista Vol II Revinter, 2005 P (81) Breznitz Z. Verbal indicators of
depression Heldref Publications. The Journal of general Psychology, Oct
1992 v 119 n 4 p 351 (13) Sadowski L, Taucher J, Steinbauer M,
Zapotoczky HG. Voice-mood: Psycholinguistic Therapy with Psychiatric
Patients. Wien Med Wochensechr. 1995; 145 (9): 201-6
P-11-04
Modulation of neuroendocrine status with different antidepressant therapies in patients of major depression
Kaviraja Udupa
Seetharamaiah Chittiprol, Kishore Kumar, Jagadisha Thirthalli, B. N.
Gangadhar, T. R. Raju, T. N. Sathyaprabha
Introduction: Major depression, a commonest psychiatric disorder is
known to involve neuroendocrine and immunological parameters viz.,
serum cortisol, ACTH and neopterin levels. However the involvement and
its modulation with different antidepressant therapies have not been very
well established. Hence we have studied the modulation of HypothalamoPituiatary-Adrenal (HPA) axis and Immune system in patients with major
depression and followed them up with various modes of antidepressant
therapies.
Method: We recruited 30 drug-nave patients of Major depression (DSMIV TR criteria) and divided them into 3 groups based on modes of treatment viz. repetitive transcranial magnetic stimulation (rTMS), selective
serotonin re-uptake inhibitors (SSRI) and tricyclic antidepressants (TCA).
Serum cortisol and ACTH were quantified based on Immuno chemiluminescence method (DPC, USA), serum neopterin was quantified by using
commercially available ELISA kits (B.R.A.H.M.S, Germany). Hamilton
depression rating scales (HDRS) and biochemical parameters were measured at basal levels and one month after therapy with respective modes.
The basal biochemical parameters were compared with age & gender
matched healthy controls.
Results: Patients showed significant elevation basal cortisol (17.31
6.1mg/dl) and neopterin levels (11.55 2.55; mean SD, nmol/l) compared to healthy controls [6.94 2.56 (cortisol) & 5.18 2.13
(neopterin)]. All the three groups of patients showed significant decrease
in cortisol and neopterin levels with one-month antidepressant therapies
but the decrease in neopterin level was significantly more in patients with
SSRI group. However, there was no correlation between biochemical
parameters and HDRS scores in all the groups.
Conclusion: Depression alters the neuroendocrine and immunological
status and the antidepressant therapies modulate its level differentially
depending on the mode of action over central nervous system. Further
studies with larger sample size and imaging studies would unravel the
mechanism of such a modulation.
References: Acknowledgements: CCRAS,India for finacial support,
B.R.A.H.M.S., Germany for providing neopterin kits, Prof.K. Taranath
Shetty,Neurochemistry for providing facilities to analyze biochemical
parameters.
P-11-05
Influence of the epileptic seizures types and antiepileptic
drugs on the development of depressive disorder in
patients with epilepsy
Enra Mehmedika-Suljic
Clinical Center, Neurology Clinic, Sarajevo, Bosnia and Herzegovina
Azra Alajbegovic, N. Loncarevic, A. Kulenovic-Dzubur, A. Bravo,
S. Alajbegovic, A. Kucukalic
Introduction: The most frequent psychic disorder, which occurs with
epilepsy, is interictal depression with a life prevalence of
40-60%. Accurate recognition of depressive disorder and its adequate
treatment contributes to an improvement of quality of life in epileptic
patients. Aim: To examine the frequency of depressive disorder in relation
to the type of epileptic seizure and the type of antiepileptic therapy in
epileptic patients.
Method: The total of 476 randomly chosen epileptic patients of both
sexes was studied at the Counseling Center of the Neurology Clinic.
Depression was assessed with the Becks and Hamiltons scales respectively.
Results: Our sample had more males (53.4%), mean age 36.712.8,
while females were slightly younger 33.312.5. Approximately 80% had
a high school diploma, significantly higher number of males was
employed (46.5:26.6 %), with x2=51.63, p<0.001, and in wedlock
x2=20.2, p< 0.001. The most frequent were seizures with partial complex
symptomatology: 33.3% in females and 24.4% in males after which follow secondary generalized seizures 26.9 %. The majority of patients were
on monotherapy with carbamazepin (52%), then follows phenobarbital
in 27.4 % males and lamotrigin in 23.8 % females. One third of patients
were on dual therapy and 3.8% of patients were on treble therapy.
Depressive symptoms on Beck scale were present in 33.6% of patients,
while the score on Hamilton scale indicated presence of the depression in
38.8% of patients.
Conclusion: Depressive symptoms were significantly more present in
middle aged women with epilepsy, unmarried and unemployed, having
epileptic seizures with partial complex symptomatology and were on dual
therapy, while significant number of males with epilepsy was on phenobarbital therapy.
109
P-11-06
Brain-derived neurotrophic factor (bdnf) levels in depressed
patients during a one-year antidepressant treatment
Mario Catena
Psychiatry, Neurobiology, Pisa, Italy
Donatella Marazziti, Armando Piccinni, Giorgio Consoli, Antonello Veltri,
Francesca Golia, Elisa Schiavi, Agnese Palla, Isabella Roncaglia,
Alessandro Del Debbio, Liliana DellOsso
Introduction: Recently the brain-derived neurotrophic factor (BDNF) has
been implicated in the neurobiology of depression. Plasma and serum
BDNF levels have been reported to be decreased in drug-free depressed
patients; however, only a few studies have evaluated the effect of antidepressants on BDNF concentrations. The aim of this study was to assess the
relationship between depressive symptoms and serum and plasma BDNF
levels during a one-year antidepressant treatment.
Method: Plasma and serum BDNF levels were assayed using the ELISA
method, in 15 drug-free patients with major depression and in 15 healthy
control subjects. Blood samples were collected at the baseline and the
2nd week, 1st, 3rd, 6th and 12th month of antidepressant treatment. The
severity of depression was evaluated at each time point by mean of the
Hamilton Depression Rating Scale (HDRS) and the Montgomery-Asberg
Depression Rating Scale (MADRS). Patients were naturalistically treated
with selective serotonin reuptake inhibitors and tricyclic antidepressants
at variable dosage (citalopram, sertraline, paroxetine, amitriptyline,
imipramine, trimipramine, desipramine) according to the clinical
response.
Results: At baseline, the mean serum and plasma BDNF levels were
19300 8800 pg/ml and 2900 1900 pg/ml, respectively, significantly
lower (p<.05) than those found in the control subjects (mean SD=
33600 8600 pg/ml and 5400 2300 pg/ml, respectively). However,
from the 1st month of treatment, patient plasma BDNF levels did not differ significantly from the values reported in healthy control subjects
(p=.079). On the contrary, at each evaluation time, serum BDNF levels in
patients were significantly lower than those of the control subjects.
Conclusion: Untreated depressed patients showed reduced baseline
serum and plasma BDNF levels, as compared with control subjects. The
normalization of plasma BDNF up to the values found in control subjects
occurred after 1 month of antidepressant treatment, in parallel with a significant improvement of the depressive symptoms. On the other hand, at
every time assessment, patients serum BDNF levels were lower than those
of control subjects: this suggests that serum BDNF might represent a nonspecific trait marker of depression.
References: Gervasoni N, Aubry J-M, Bondolfi G, Osiek C, Schwald M,
Bertschy G et al (2005): Partial normalization of serum brain-derived neurotrophic factor in remitted patients after a major depressive episode.
Neuropsychobiol 51:234-238.
P-11-07
Quetiapine as add-on therapy in the treatment of patients
with major depressive disorder
Ion-George Anghelescu
Charite, Psychiatry, CBF, Berlin, Germany
Introduction: Patients with major depressive disorder (MDD) accompanied by physical symptoms may be less responsive to antidepressant treatment. While quetiapine has been evaluated in the treatment of bipolar
depression, data on the efficacy of quetiapine as an initial combination
drug for unipolar depression are not yet available. The aim of the present
study was to evaluate the efficacy of quetiapine as adjunctive therapy to
the SSRI citalopram in patients with MDD and somatic complaints.
Method: 34 inpatients with nonpsychotic DSM-IV MDD experiencing significant symptoms of somatic distress as defined by a baseline score on
the SCL-90-R somatization subscale greater one SD above adult nonpatient norms were randomly assigned to receive either citalopram
40 mg/day plus placebo (n=16) or citalopram, 40 mg/day plus quetiapine,
300 to 600 mg/day (n=18) for 6 weeks. The primary outcome measure
was the Hamilton Depression Rating Scale (HDRS) score.
Results: There were no significant differences between treatment
groups. Mean changes in HDRS scores from baseline to week 6 using lastobservation-carried-forward methods were -12.45.91 and -10.95.5 in
110
the citalopram-quetiapine and citalopram-placebo group, respectively.

Response rates were 61.1% for the citalopram-quetiapine and 50.0% for
the citalopram group alone. The combination of quetiapine and citalopram was generally well tolerated.
Conclusion: Although quetiapine as add-on to citalopram did not separate statistically from placebo on the HDRS score in improving depressive
symptoms in patients with MDD and somatic complaints, trends in
response rates and second outcome parameters showed advantages for
quetiapine. Larger, double-blind, placebo-controlled trials of quetiapine
as augmentation therapy in MDD are needed.
P-11-08
Anabolic balance in depression: Influence of antidepressants
Yakov Kochetkov
Moscow Institute of Psychiatry, Psychoneuroendocrinology, Russia
Introduction: Some researchers suppose that cortisol/DHEAS ratio and
growth hormone (GH) are important markers of anabolic balance. The
aim of the study was to investigate cortisol, DHEAS and GH levels in
depressed patients with antidepressant treatment.
Method: There were examined 39 patients with depressive episode
(F 32.2). Patients in the first group (n=25) had antidepressant treatment
of tianeptine during three weeks in the average dose of 37,5 mg per day.
Patients in the second group (n=14) had treatment of sertraline in the
average dose of 50 mg per day. Depressive symptoms were evaluated by
the Hamilton Depression Scale (HDS). Blood samples were drawn two
times: before antidepressant treatment, and on 21 day of the treatment.
Serum DHEAS, cortisol and growth hormone levels were measured using
immune-enzyme method.
Results: There was a negative correlation between DHEAS level and score
by the HDS before treatment (rs = - 0,47, p=0,037). Cortisol/DHEAS ratio
in patients after tianeptine treatment was significantly low than before
treatment (accordingly 258 and 394, P = 0,002). In patients under sertraline treatment these differences were also significant (accordingly
339 and 419, p=0,04), but after tianeptine treatment cortisol/DHEAS
ratio was significantly low than after sertraline treatment (accordingly
258 and 339, p=0,003). Decrease in the cortisol/DHEAS ratio was correlated with improvement of depressive symptoms, measured by HDS
(rs = 0,42, p=0,045). GH level on the 21st day of therapy significantly
increased both in patients under tianeptine treatment (2,880,83 ng/ml)
and sertraline treatment (2,540,6 ng/ml) in comparison with GH levels
in these groups before treatment (accordingly 1,310,2 and 1,44
0,35 ng/ml, p=0,03).
Conclusion: Our results demonstrate that antidepressants influence on
anabolic balance in depression, decreasing cortisol/DHEAS ratio and
increasing GH level. The influence of the tianeptine on cortisol/DHEAS
ratio is marked more than sertraline.
References: Wolkowitz O.M., Epel E.S., Reus V.I. (2001) Stress hormonerelated psychopathology: pathophysiological and treatment implications.
World J Biol Psychiatry 2: 115-143. Young A.H, Gallagher P, Porter R. J
(2002) Elevation of the cortisol-dehydroepiandrosterone ratio in drug-free
depressed patients. Am J Psychiatry 159:1237-1239.
P-11-09
Effect of serotonin receptor 2A gene polymorphism on
mirtazapine response in major depression
Myoung-Jin Choi
Korea University, Depression Center, Seoul, Republic of Korea
Jong-Woo Paik, Min-Soo Lee
Introduction: This study was to determine the relationship between the
-1438A/G polymorphism of the 5-HTR2A gene and the response to mirtazapine in a Korean population with major depressive disorder.
Method: Mirtazapine was administered for 8 weeks to the 101 patients
who completed this study. All subjects were examined using the
Structured Clinical Interview for DSM-IV. The severity of depression was
assessed using the 21-item Hamilton Depression Rating (HAM-D-21)
scale. Only subjects with a minimum score of 18 on the HAM-D-21 scale
entered the study. Their clinical symptoms were evaluated with the HAMD-21 scales at baseline and after 1, 2, 4 and 8 weeks of treatment.
Results: A main effect of genotype or an effect of genotype time interactions on the decrease in HAMD score during the 8-week follow-up was
not found, which suggests that the 5-HTR2A -1438A/G polymorphism
does not affect the clinical outcome to mirtazapine administration.
However, significant effects of genotype and allele carriers on the
decrease in the sleep score over the 8 weeks were found (genotype:
F=4.093, p=0.017; allele: F=4.371, p=0.037), whereas no effect of genotypetime interactions on the decrease in the HAMD score over the
8-week follow-up was found. These observations suggest that the 1438A/G polymorphism affects the sleep improvement but not the sleep
pattern over time. A t-test-based evaluation of the effect of the 5-HTR2A
-1438A/G polymorphism on the sleep improvement at each time period
revealed significant differences in the sleep scores after 2 weeks of mirtazapine administration. The sleep scores were lower for carriers of the
A+ allele than of the A allele after 2 weeks of mirtazapine administration (p=0.041).
Conclusion: Although the -1438A/G polymorphism affects the sleep
improvement resulting from the administration of mirtazapine to Korean
patients with major depressive disorder, our results do not support the
hypothesis that this polymorphism of the 5-HTR2A gene is involved in the
therapeutic response to mirtazapine.
References: Sato, K., Yoshida, K., Takahashi, H., Ito, K., Kamata, M.,
Higuchi, H., Shimizu, T., Itoh, K., Inoue, K., Tezuka, T., Suzuki, T., Ohkubo,
T., Sugawara, K., Otani, K., 2002. Association between -1438G/A promoter polymorphism in the 5-HT(2A) receptor gene and fluvoxamine
response in Japanese patients with major depressive disorder.
Neuropsychobiology 46, 136-140.
P-11-10
Comparison between prevalence and severity of depressive
symptoms among tick borne encephalitis patients in an
acute phase of the neuroinfection and three month later
Dariusz Juchnowics
Medical University Bialystok, Dept. of Psychiatry, Choroszcz, Poland
Anna Agnieszka Tomczak
Introduction: The objective of the study was evaluation of the frequency
and severity of depressive symptoms in an acute phase of tick-borne
encephalitis (TBE) and three months later. Earlier studies indicated higher
occurrence of depressive symptoms in TBE patients.
Method: We examined TBE patients two times. The first examination was
performed during their hospitalisation at Infectious Department of
Medical University in Bialystok and infectious wards in Hajnowka and
Bielsk Podlaski (North-Eastern Poland). The second examination was conducted three months after an acute phase of the neuroinfection- all of
subjects during the second examination were outpatients. There were 51
subjects - 31 men and 20 women; ages: 21 to 74 (average 44.8). TBE was
serologically confirmed in all examined. Subjects did not receive any psychiatric care before the onset of the neuroinfection. They were evaluated
according to the Hamilton Depression Rating Scale (HDRS) and Beck
Depression Inventory (BDI). 31 control healthy subjects were also examined two times with three months interval.
Results: In our group TBE patients had significantly higher frequency of
depressive symptoms during two examinations in comparison to healthy
controls- especially in the severe course of the neuroinfection. During the
second examination TBE patients had even significantly more depressive
symptoms in comparison to the first evaluation in an acute phase of the
neuroinfection. Among the most frequent depressive symptoms were:
depressed mood, insomnia, difficulties at work and loss of interest, anxiety and loss of weight. Those symptoms were more frequent and severe
in patients with more severe course of TBE.
Conclusion: TBE patients should be examined by psychiatrist and often
need psychiatric treatment especially after recovery from an acute phase
of TBE.
P-11-11
Personality and the prediction of response in major
depressive disorder: A randomized control trial comparing
cognitive therapy and pharmacotherapy
R.M. Bagby
University of Toronto, Addiction & Mental Health, Canada
L. C. Quilty, Z. V. Segal, C. C. Mcbride, S. H. Kennedy, P. T. Costa
Introduction: While a number of interventions have demonstrated efficacy in the treatment of Major Depressive Disorder (MDD), a substantial
proportion of patients fail to respond or achieve only partial response to
the treatment they receive. Personality traits may provide a way in which
to understand this variability in response rates, and to optimize treatment
success through the identification of which patients are more likely to respond best to which treatments. The objective of this investigation was to
determine if the personality traits of a comprehensive taxonomy of personality are predictors of response to either cognitive therapy (CT) or pharmacotherapy (PT).
Methods: 173 patients diagnosed with MDD were randomized to receive either CT or PT over 16-26 weeks. Participants completed the Hamilton
Rating Scale for Depression and the Revised NEO Personality Inventory
prior to and following treatment. Hierarchical linear regressions were conducted to determine if treatment response to different treatment modalities was moderated by different personality traits. Cut-off values for the
dichotomized personality scores were derived using regression tree analyses. 2 and Fishers Exact tests assessed differences in response rates;
t-tests were used to assess group differences.
Results: Four personality traits -- Neuroticism, Angry Hostility, Trust and
Straightforwardness -- were able to distinguish differential response rate
to CT or PT. Patients with higher scores on Neuroticism and Angry
Hostility, a facet of Neuroticism, are more likely to respond to PT vs. CT.
Patients scoring higher on Trust facet trait, a facet of Agreeableness, were
more likely to respond in response to CT compared to low scorers on the
Trust; this trait had no bearing on response for those treated with PT.
Patients scoring low on Straightforwardness, another facet of
Agreeableness, had a higher response rate to PT compared to high scorers
on the Straightforwardness; this trait had no bearing on response for
those treated with CT.
Conclusion: Participants did not response equally to the treatments provided; indeed, personality traits predicted differential response to CT vs.
PT. The assessment of patient personality traits holds may assist in the
selection and subsequent optimization of treatment response for depressed patients.
P-11-12
Increased cutaneous blood flow but decreased response to
stressors in depressed mood
Shih-Tsung Cheng
Kaohsiung Medical University H, Dermatology, Taiwan
Chiao-Li Ke, Weichi Lin
Introduction: Cutaneous blood flow (CBF) could be greatly decreased
during the stressor test, according to our previous study. The mechanisms
were unknown but sympathetic sphincter control may play a role. The
aim of this study was to examine the relationship between depressed
mood and sympathetic control of CBF in health men and women at rest
and during two stressors.
Method: Forty healthy college students completed a laboratory stress
protocol that included a 5-minute baseline resting period, a challenging
2-minute Troop test as stress task, a 3-minute recovery period, a 2-minute
7-series calculation test as second stress task, and then a 3-minute recovery period. Hypertension, diabetes mellitus, cardiac or neurological diseases, major life events and participation in competitive athletic activity
within 3 months prior to the study, and caffeine, nicotine, and alcohol use
within 12 hours prior to the experiment are exclusion criteria. Depressed
mood was assessed using the Taiwanese Depression Questionnaire (TDQ),
which is specifically designed for the assessment of depression in
Taiwanese. CBF of first, middle, and third fingers was measured by laser
Doppler flowmetry. We used the statistical methods of repeated analysis
of variance to assess the difference of CBF response to stress between
depressed and euthymic groups.
111
Results: Participants were categorized as having a euthymic mood or

depressed mood on the basis of cut-off-point (>10 and <=10) splits of
their TDQ scores. Those in the depressed mood group with high TDQ
score had greater CBF at rest and during both stressor tests than the
euthymic mood group with low TDQ score, achieving statistically significant level at first (F=7.808,P=0.00), middle (F=6.449,P=0.00), and third
finger (F=5.87,P=0.00). The depressed group had decreased response of
CBF to both stressor tests than the euthymic group, although it does not
reach statistically significant level.
Conclusion: Depressed mood is related to the magnitude of cutaneous
blood flow. The observation of increased blood flow at rest and during
stressors and decreased response to stressors may be contributed by dysfunctional autonomic function in depressed mood. The results of our
study suggested cutaneous blood flow might be a useful adjuvant test in
evaluation of depressed moods.
P-11-13
Synergistic Physico Psychotherapy (SPPT) - a new approach
for neuropsychiatric patients
Werner N. Morokutti
Private Practice, Wagna, Austria
Introduction: More than 100 years ago the Austrian scientist S. Freud
founded the Psychoanalysis. 50 years ago the American scientist J. Lilly
invented the Samadhi-Tank. Both ideas together led to the treatment of
neuropsychiatric patients by SPPT. The first step of therapy is a body orientated treatment in the Isolation Tank. During the floating phase in the
solution of magnesium sulphate you get into a state of trance and you
will loose the feeling of your body as well as the sensation of time and so
muscle tensions will disappear and you will get in a status of sensoric deprivation. Simultaneous to the physical effect on the body free associations
on the psychic level are achieved in the firs step of treatment. After
approx. 45 minutes the floating phase comes to an end and the assistant
will show the client into a writing room where he can write down his
experiences, the thoughts and the feelings he had in the tank (second
step of therapy). After he has finished the report, the client will discuss
the report in a psychotherapeutical session with the therapist (3rd step of
treatment). The SPPT can help against stress, muscle tensions, neck- and
spinal pain, psychosomatic dysfunction, depression end exhausting syndrome. The results of SPPT are encouraging and we should try to integrate the holistic idea of neuroscience and philosophy again as it was till
300 years ago and I think that SPPT can contribute to that. One benefit
for the therapist should to be mentioned, during more than 50% of the
patients treatment time, the therapist is able to do other things.
References: 1. Sigmund Freud - Werksausgaben in 2 Bnden - S.Fischer
1978 2. John C. Lilly - Programming and Metaprogammingin the Human
Biocomputer - Julian Press, NY 1967 3. Alexander u. Leslie Lowen Bioenergetik - Goldmann Verlag,1990 4. W.Pieringer u. Ch. Fazekas - Die
vier primren Erkenntnismethoden - Als wissenschaftliche Leitlinien fr die
Selbsterfahrung in der Psychotherapie-Ausbildung Psychotherapieforum Springer Verlag 1996 5. Eric R. Kandel - Psychiatrie, Psychoanalyse und die
neue Biologie des Geistes - Suhrkamp Verlag 2006
P-11-14
Affective disorders and solar activity. 16 years follow up
Fernando Ivanovic-Zuvic
Santiago, Chile
Rodrigo De la Vega, Nevenka Ivanovic-Zuvic, Eduardo Correa
Introduction: The present work discusses the link between solar activity
and appearance of affective disorders. Solar activity is reflected by the
Wolf number, which is given by the formula R= K(10g+f), where g
stands for the groups of sunspots and f is the total number of
sunspots.
Method: We examined 1862 clinical files at the Clnica Psiquiatrica
Universitaria, Santiago de Chile. Patients with mayor depressions and
manic disorders were considered, but only those admitted at the clinic for
the first time. We examined the correlation between years of hospitalization and average Wolf numbers for those years, and this for the period
1990-2005, which corresponds to approximately one and half solar cycles
of 16 years.
112
Results: A big number of hospitalizations of depressive patients occurred

during years of low solar activity, and there was a slight increase in the
number of manic patients during years of high solar activity. Depressive
disorders showed a negative correlation with solar activity, the Spearman
coefficient being equal to -0.812 (p=0.000). Manic disorders showed a
positive correlation with the Spearman coefficient, equal to 0.399
(p= 0.063) close to statistical significance.
Conclusion: Depressive disorders have a significant inverse correlation
with solar activity, while manic disorders showed a positive correlation,
but without statistical significance.
References: Rosen LN, Targum SD, Terman W, Bryantt MJ, Hoffman H,
Kasper SF et al. Prevalence of seasonal affective disorder at four latitudes.
Psychiatry Res 1990; 31:131-44 Ivanovic-Zuvic F, De la Vega R, IvanovicZuvic N, Renteria P. Enfermedades afectivas y actividad solar. Actas Esp
Psiquiatr 2005; 33 (1): 7-12 Magnusson A. An overview of epidemiological studies on seasonal affective disorder. Acta Psychiatr Scand 2000;
101: 176-84.
ANXIETY - Poster
P-03
Anxiety
P-03-03
Personality traits in social phobia patients: Changes after
successful treatment
T4 Anxiety
Mariangela Gentil Savoia

Institute of Psychiatry, Univ., Anxiety Clinic, Sao Paulo, Brazil
Tito Paes de Barros Neto, Fabio Corregiari, Marcio Bernik
P-03-01
Duloxetine as an effective treatment for adults with generalized anxiety disorder: A pooled analysis
Susan Ball
Eli Lilly and Company, Lilly Research Laboratories
James Russel, Christer Allgulander, James Hartford, Erickson Janelle,
Michael Detke, Moria Rynn
Introduction: Duloxetine [Cymbalta] is a serotonergic noradrenergic
reuptake inhibitor that demonstrated efficacy in each of 3 independent
studies for treatment of adults with generalized anxiety disorder (GAD). A
pooled dataset provides here the best approximation of clinical outcomes
with duloxetine treatment for GAD.
Method: Data were summed from 3 double-blind, placebo-controlled trials of duloxetine (DLX) treatment; 2 studies were 10-week flexible dose
60 to 120 mg/day and 1 study was 9 week fixed dose 60 or 120 mg/day.
Inclusion/ exclusion criteria and measures were the same across studies.
The primary efficacy measure was Hamilton Anxiety Scale (HAMA) total
score. Secondary measures included the Hospital Anxiety Depression
Scale (HADS) and response and remission rates. Functional outcome was
assessed by the Sheehan Disability Scale (SDS). Treatment group differences for continuous variables were analyzed using ANCOVA model
(treatment, study as main effects; baseline score as covariate).
Results: Across the studies, patients were randomly assigned to duloxetine (N=668) or placebo (N=495). Mean age = 42.4 yrs; 65% female. On
each measure, duloxetine-treated patients were more improved than placebo-treated patients (all comparisons, P.001): (insert table)
Treatment-emergent adverse events for duloxetine (5% and twice placebo rate) were: nausea (DLX 38.5%, PLA 10.3%); dizziness (DLX 14.5%,
PLA 7.7%); dry mouth (DLX 11.8%,PLA 3.8%); fatigue (DLX 11.5%, PLA
3.6%); constipation (DLX 9.6%, PLA 3.2%); insomnia (DLX 8.2%, PLA
2.8%); somnolence (DLX 8.2%, PLA 1.8%); hyperhidrosis (DLX 7.5%,
PLA 2.2%); and decreased libido (DLX 5.8%, PLA 1.4%) (all comparisons,
P.001).
Conclusion: With a pooled sample of over 1100 patients with GAD,
duloxetine was effective for reducing the severity of anxiety symptoms
and for increasing patients overall role functioning.
P-03-02
Adherence to treatment in social phobia patients predictors
Mariangela Gentil Savoia
Institute of Psychiatry, Univ., Anxiety Clinic, Sao Paulo, Brazil
Tito Paes de Barros Neto, Andrea Machado Vianna, Fabio Corregiari,
Marcio Bernik
Introduction: The relationship between adherence to group cognitive
behavior treatment and to pharmacological treatment with SRSI was
examined for 144 social phobia patients.
Method: The features evaluated like predictors of adherence to treatment were: personality traits, personality disorders, social skills and
depression.
Results: The results are discussed in terms of factors affecting adherence
in social phobia treatment. The features with relationship between adherence and treatment was depression and personality traits.
Introduction: This study evaluate personality traits of social phobic subjects before the treatment and evaluate the score of the respondents after
the treatment based on Clonningers Temperament and Character
Inventory (TCI).
Method: 108 subjects, ranging in age from 18 to 65 years old, who fulfilled the criteria of social phobia in DSM IV were randomly allocated into
one of the 4 groups of treatment in a double-blind clinical trial.
Responders were reevaluated, after a 20- week treatment with sertraline,
placebo, cognitive behavior therapy and support psychotherapy. The classification of respondents patients took into account the SAD and CGI
results.64 subjects were considered responders. These patients were
called six months after the conclusion of the treatment and were reevaluated with TCI test.
Results: Patients with social phobia showed different average value in
the items NS, HA,P,SD e ST comparing to those population in which the
test was validated. This study suggests a high overlap between the
description of common personality traits and axis I symptom profile
according to DSM IV and a high correlation of the diagnosis of social phobia with deviations in TCI dimensions. Responders have showed personality traits change both in temperament and character, according to the
author of the test. Temperamental changes were related to pharmacological treatments, and characters changes were related to psychotherapy
treatments.
P-03-04
Association study between the brain-derived neutrophic
factor gene Val66Met polymorphism and early onset social
anxiety disorder
Se-Won Lim
Kangbuk Samsung Hospital, 108, Pyung-dong Chongro-gu, Seoul,
Republic of Korea
Kang-seob Oh, Min-soo Lee
Introduction: Several lines of evidences suggest that the brain-derived
neutrophic factor (BDNF) may play role in the pathophysiology of depression and anxiety. We analyzed the association of BDNF gene polymorphism 196G>A (val66met) in the coding region of exon XIIIA and early
onset social anxiety disorder(SAD)
Method: 75 patients with SAD and 152 comparison subjects were tested for BDNF (val66met) polymorphism. Clinical interview and MINI international neuropsychiatric interview was conducted by trained psychiatrist
for diagnosing DSM-IV social anxiety disorder. We included only early
onset (onset before 18 years of age) SAD patients. There were no significant differences in age between two groups.
Results: There were no significant differences in the frequency of the
genotype (2=1.09, df=2, p=0.58), or allele (2=0.00, df=1, p=0.97)
between patients and controls. In addition, when this comparison was
conducted separately by gender, there were no significant difference
between SAD and controls.
Conclusion: These results in our Korean sample suggest that the BDNF
(val66met) polymorphism does not play significant role in susceptibility of
SAD.
P-03-05
Involvement of adenosinergic receptors in anxiety related
behaviours
Shrinivas Kulkarni
University Institute of, Pharmaceutical Sciences, Chandigarh, India
M. Bishnoi, K. Singh
Introduction: Adenosine is considered as one of the inhibitory modulator in the central nervous system, similar only to well accepted inhibitory
Gamma Amino Butyric Acid (GABA). Unlike GABA the role of adenosine
in the modulation of anxiety state is still not clear.
113
ANXIETY - Poster
Methods: In the present study we have studied the effect of adenosine

(A1 and A2 receptor agonist), caffeine (A2A receptor antagonist), theophylline (A2A receptor antagonist) and their combination in anxiety related behaviours using elevated zero maze and elevated plus maze paradigms and compared their various behavioural profiles.
Results: Adenosine (10, 25, 50,100 mg/kg) significantly showed anxiolytic effect at all the doses where as caffeine (8, 15, 30, 60 mg/kg) and
theophylline (30, 60 mg/kg) showed psychostimulatory action at lower
doses and anxiogenic effect at higher doses. Pretreatment with caffeine
(8, 15, 30 mg/kg) and theophylline (30 mg/kg) reversed the anxiolytic
effect of adenosine.
Conclusion: The study suggests the involvement of adenosinergic receptor system in anxiety related behaviours.
P-03-06
Predictors of clinical outcome in panic disorder: Analysis of
short-term Venlafaxine XR treatment studies
Jeff Musgnung
Wyeth Pharmaceuticals, Global Medical Affairs, Collegeville,
Pennsylvania, USA
Mark Pollack, Dan Stein, Richard Mangano, Richard Entsuah, Naomi
Simon
Introduction: This pooled analysis evaluated the predictors of clinical
outcome in the short-term treatment of panic disorder.
Method: Data were pooled from 4 randomized, placebo-controlled studies of venlafaxine XR in adult outpatients with Diagnostic and Statistical
Manual of Mental Disorders, Fourth Edition (DSM-IV) panic disorder with
or without agoraphobia (n=1595). Patients were randomly assigned to
10 to 12 weeks treatment with either placebo or venlafaxine (fixed or
flexible dosing, range from 75 mg/d to 225 mg/d). The primary efficacy
measure was the proportion of patients free of full-symptom panic
attacks at end point. Predictors included panic severity (full-symptom
panic attack frequency <8 or =8 panic attacks during each 2 week period
in the 4 weeks prior to baseline) and gender. Other predictors included
baseline severity on clinical ratings of panic disorder, clinical global
impressions, anxiety, somatic and psychic anxiety, depression, mood, phobias, fear, and avoidance.
Results: In both the active treatment and placebo groups, males (65%
and 50%, respectively) and those with low symptom severity (69% and
53%, respectively) were significantly (P<0.05) more likely to be panic-free
at end point. For nearly all baseline ratings on clinical measures, greater
symptom severity was associated with lower proportions of patients who
were free from full-symptom panic attacks at end point. Change scores
showing improvement in symptom severity following treatment were
associated with higher proportions of patients who were free from fullsymptom panic attacks at end point.
Conclusion: Panic-free status at end point was predicted by gender,
panic disorder severity, and most baseline and change scores of clinical
ratings scales.
P-03-07
Response and remission rates with Venlafaxine XR and
Placebo in social anxiety disorder: Effects of gender and
physical symptoms
Jeff Musgnung
Pennsylvania, USA
Michael Liebowitz, Jonathan Davidson, Carlos Blanco, Raj Tummala,
Qin Jiang
Introduction: This pooled analysis compared the efficacy of venlafaxine
extended-release (XR) versus placebo in the treatment of social anxiety
disorder (SAD).
Method: Data were pooled from 5 randomized studies of patients with
Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition
(DSM-IV) SAD (n=1459) who were treated with venlafaxine XR 75 mg/d
to 225 mg/d or placebo for 12 weeks (4 studies) or 28 weeks (1 study).
Response and remission rates were calculated for the overall sample, as
well as stratified by gender and level of physical symptom severity at base-
114
line. Response was defined as a score of 1 or 2 on the Clinical Global

Impressions-Improvement (CGI-I) scale. Remission was defined as a total
score of <30 on the Liebowitz Social Anxiety Scale (LSAS).
Results: At baseline the mean LSAS score was 88.1 and 86.6 for the venlafaxine and placebo arms, respectively. Overall response rates at week 12
were 55% for venlafaxine XR and 33% for placebo (P<0.0001); remission
rates were 25% and 12%, respectively (P<0.0001). Among patients with
less severe physical symptoms, response rates were 52% and 32% for
venlafaxine XR and placebo, respectively (P<0.0001); remission rates were
27% and 14%, respectively (P<0.0001). Response rates among patients
with more severe physical symptoms were 56% for venlafaxine XR and
33% for placebo (P<0.0001); remission rates were 24% and 11%,
respectively (P<0.0001).
Conclusion: Venlafaxine XR is effective in the treatment of SAD, regardless of gender or severity of physical symptoms.
P-03-08
Cutaneous blood flow decrease in response to psychological stress
Chiao-Li Ke
Kaohsiung Medical University, Psychiatry, Taiwan
Cheng Shih-Tsung, Ming-Jen Yang, Weichi Lin
Introduction: The close link between affective disorders and vascular diseases has been observed. It has been found that psychological stress
contributes to vascular diseases. Assessment of cutaneous blood flow
(CBF), which is highly accessible, could provide insight into stress related
physiologic and pathological changes of blood vessels. The aim of this
study is to investigate the change of sympathetic control of CBF under a
programmed stress protocol in healthy subjects.
Method: Forty healthy college students completed a laboratory stress
protocol that included a 5-minute baseline period, a 2-minute Stroop test
as stress task, a 3-minute recovery period, a 2-minute 7-series test as second stress task, and then a 3-minute recovery period. Hypertension, diabetes mellitus, cardiac or neurological diseases, major life events and participation in competitive athletic activity within 3 months prior to the
study, and caffeine, nicotine, and alcohol use within 12 hours prior to the
experiment are exclusion criteria. Laser Doppler flowmetry were performed to measure cutaneous blood flow of first, middle, and third fingers. A repeated analysis of variance was used to exam the effect of
stress.
Results: CBF reached peak level after 5 minutes of rest, dropped abruptly at the first minute of 2-min stress tasks in response to color-naming
challenge in Stroop test, then slightly elevated in the second minute of
the test. During the subsequent recovery period, CBF gradually returned
to the peak level. The same dynamics of CBF could be observed during
the following calculation test and recovery period (F=7.808, P=0.000).
Conclusion: Cutaneous blood flow could be greatly decreased during
the stressor test. The mechanisms were unclear but sympathetic sphincter control may play a role. The observation of immediate CBF decrease
in response to stressors may reflect the physiological compensation of
shunting blood to central organs, and the immediacy of this response
might exclude other possible flow-decreasing factors such as oxygen consumption, vasoconstricting metabolites, blood pressure, or body temperature, those of which may exert delayed effect on CBF. Our findings suggested CBF is a potential assessment of stress in mental health screening,
mental status examination, and stress management for facilitating mental health maintenance. The results of this study could be applied to
further studies of stress related physiologic and pathological changes of
blood vessels and to issues of vascular pathogenesis in affective disorders.
P-03-09
Open-label trial of gabapentin in generalized anxiety disorder
Guillermo Rivera
Santa Cruz, Bolivia
Introduction: There is a need to identify novel pharmacotherapies for
anxiety disorders. The authors examined the safety and efficacy of
gabapentin, in adult outpatients with generalized anxiety disorder.
ANXIETY- Poster
Method: In an 8-week, open-label, fixed-dose study, 18 medically

healthy patients with DSM-IV generalized anxiety disorder received treatment with gabapentin (1200 mg/day) following a 2-week drug-free period. The primary efficacy measure was the Hamilton Anxiety Rating Scale
(HAM-A) score at endpoint.
Results: Twelve of the 15 patients who completed the trial responded
positively to gabapentin. At 8 weeks, eight of the 15 patients had HAMA score indicating remission of their anxiety. The median time to response
was 2.5 weeks.
Conclusion: Gabapentin appears to be an effective, well-tolerated, and
rapidly acting anxiolytic medication for some patients with generalized
anxiety disorder. Larger, placebo-controlled studies are indicated.
P-03-10
Effect of maternal separation on locomotor activity of
female adult rats
Introduction: There is evidence that maternal separation of neonatal rats
may influence emotional behavior. Early maternal deprivation is considered an animal model of early life stress that may cause persistent alterations in adult behaviors (I-3). The purpose of this study was to investigate the long-term effect of daily maternal separation, Days 5-15, on
locomotion and exploration in female adult rats.
Method: Female Wistar rats and their female pups were reared under
3 conditions: 1) 360 min daily maternal separation, 2) handling by man
for 5 min daily both conditions were done on the first 10 days after birth
and 3) no handling or separation. At 21 days of age rats, were housed in
each group for 4 weeks. Subsequently, rats were tested individually for
5 min in a circular open field arena.
Results: The results demonstrated that both handling and maternal separation, produced hyperlocomotion (increased total zone transition) and
exploration activity (increased number of rears). Both effects were significantly increased in handling group when compared with control group
(no handling or separation).
Conclusion: These findings suggested that maternal separation alters
long-term effect on locomotion and exploration behaviors of female adult
rats.
References: 1. Suarez, M., Molina, S., Rivarola, M.A., Perassi, N.I. (2002)
Life Sci. 71:1125-37. 2. Shalev, U. and Kafkafi, N. (2002) Pharmacol
Biochem Behav. 73:115-22. 3. Wongwitdecha, N. and Yoopan, N. (2005)
Australian & New Zealand Journal of Psychiatry, 39(Suppl 2): A74-A75.
P-03-11
The treatment of conversion disorders wieh second generation antipsychotic
Alexandru Tiugan
Emergency Military Hospital, Psychiatry, Craiova, Romania
Radut Claudia
Introduction: The use of antipsychotic in conversion disorder is in accordance with biochemical support, functional interactions playing an important role at junction level for different neuromediator lines. The conversion disorder, especially the one with associated factors for unfavourable
prognosis, suggest using a therapeutic scheme with a relatively rapid
impact on the symptom and finding a method to improve the negative
prediction in the evolution of the disorder. Through its prevalence
(10-15% of cases presented in ambulatory) and its recurrence, the conversion disorder implies diversified therapeutic approaches, that can influence the evolution and prognosis of the disorder. Besides suggestion and
persuasion, we must also act on the inhibiting/exciting cerebral mechanisms in the cerebral trunk and reticulated substance, especially through
atypical antipsychotic with large receptor range (Olanzapine, Clozapine).
Method: In the period 2000-2006 we studied 150 patients fulfilling the

diagnosis criteria according to DSM-R for the conversion disorder. 50
patients were treated with small doses of conventional antipsychotic
(haloperidol 2,5-5mg/day), 50 patients with symptomatic, suggestion and
persuasion, and the rest with non-conventional antipsychotics (25
patients with olanzapine 2,5-5mg/day), 25 patients with clozapine-25100mg/day.
Results: From the first days of treatment the conversion symptomatology
(especially the one with neurological symptoms) improved both under
treatment with olanzapine as well as for the lot treated with clozapine,
compared with the lot treated with haloperidol. The lot treated with suggestion, persuasion and symptomatic, although the initial response was
favourable, after a few days, it exacerbated in a psycho-conflictual context, asking for a treatment of 5 mg/day olanzapine. The differences
appeared regarding recurrences. If in the lot treated with atypical antipsychotic these were rare (3-4 years), in the lot treated with conventional
antipsychotic, these were more frequent (more than 10 in 5 years).
Conclusion: Without generalizing the therapeutic approach with small
doses of second generation atypical antipsychotics, the above enunciations prove the opportunity of using these in association with complementary therapies or as an alternative for these. Usage of the second
generation atypical antipsychotic represents a way to improve the negative prediction in the evolution of the conversion disorder, reducing the
rate of relapses even in a psycho-conflictual context.
P-03-12
Spectral analysis of EEG in personality disorder subjects
Ana Agustina Calzada Reyes
Instituto de Medicina Legal, Psiquiatria Forense, Ciudad Habana, Cuba
Introduction: Functional alterations of the Central Nervous System constitute one of the neurobiological related factors to personality disorders
Methods: The resting electroencephalogram was recorded in 18 subjects,
with personality disorders evaluated for forensic psychiatrics
(Experimental Group). They were compared with 10 subjects without personality disorders (Control Group). The features at visual inspection of the
Electroencephalogram and the use of frequency domain quantitative analysis techniques (Broad Band and Narrow Band Spectral Measures) are
described.
Results: 53,6% of personality disorder subjects had electroencephalographic abnormalities. The most frequent were the background activity
organizational alterations, low amplitude electrogenesis, an attenuated
alpha rhythm and sometimes barely incipient. Delta-theta slow activity in
the frontal lobe. The quantitative analysis showed differences between
the frequency spectrums and between the broad band spectral measures
from both groups and between experimental groups and the Cuban
norms. The Delta-theta frequencies predominate in the personality disorders whereas the alpha activity did it in the Control Group.
Conclusion: A high incidence of electroencephalographics abnormalities
were found in the personality disorder subjects. The most frequents were:
electrogenesis alterations, attenuated alpha rhythm and delta-theta slow
activity in the frontal lobe. In the quantitative analysis the delta-theta frequencies predominate in the personality disorders and the alfa activity did
it in the Control Group.
References: 1.1. Moya-Albiol L. Bases neurales de la Violencia. Rev
Neurol 2004; 38(11):1067-1675.2. Lopez- Muoz F, Alamo C, Cuenca E.
Bases neurobiolgicas de la agresividad. Arch Neurobiol . 2000; 63:197220. 3. Gatzke-Kopp, Raine A, Bushsbaum, LaCasse L. Temporal Lobe
deficits murderers: EEG finding undetected by PET. Neuropsychiatry Clin
Neurosci. 2001;13(4): 486-491.4. Brennan PA, Raine A. Biosocial bases of
antisocial behaviour: psychophysiological, neurological, and cognitive
factors. Clin Psychol Rev. 1997;17(6):589-6045. Bigler ED. Frontal lobe
pathology and antisocial personality disorder. Arch Gen Psychiatry.
2001;58 (6):609-11.
115
ANXIETY - Poster
P-03-13
Metabolic syndrome and combat post-traumatic stress disorder
P-23
Anxiety II
Miro Jakovljevic
Dragan Babic, Marko Martinac, Marija Saric, Radmila Topic, Boris Maslov
T4 Anxiety
Introduction: There has been a growing interest in the effect that comorbid mental and somatic disorders may have on each other. Post-traumatic stress disorders (PTSD) have been associated with co-morbidity of
many major somatic and mental disorders as well as with premature mortality. The objective of this study was to examine the relationship between
combat-related PTSD, metabolic syndrome and its components.
Method: Metabolic syndrome and its components as well as co-morbid
somatic disorders were investigated in 147 male war veterans with combat PTSD and in 79 males who needed medical attention in family medicine dispensary.
Results: Only 4.25% of our patients were without any co-morbid somatic and mental disorders, metabolic syndrome or any its component.
Metabolic syndrome according NCEP: ATP III was found in 27.2 % of our
PTSD patients. Intensity of post-traumatic syndrome and post-traumatic
stress syndrome was significantly related. Metabolic syndrome was identified in 51.9% of the war veterans with high intensity of PTSD in comparison with 15.1% of the veterans with low intensity PTSD.
Conclusion: Our findings have important clinical implications. PTSD is
multi-systemic disorder. Treatment of war veterans with PTSD should
address co-morbid somatic disorders including metabolic syndrome as
well as the clinical features of PTSD.
P-03-14
Two bio-psychosocial profiles as short-term outcomes of a
pain management program in chronic pain and stress related disorders grouped by low salivary cortisol or low
serum pancreas polypeptide
Kamilla Portala
RCT, Research Dept., Copenhagen, Denmark
Introduction: This study includes all patients (age 18-70) with treatmentrefractory chronic pain and stress related disorders that had been referred
to and terminated an in-patient multiprofessional and multidisciplinary
pain management (In-MMPM) program April 2003 to May 2006 at the
Pain Centre in the University Hospital in Uppsala, Sweden. The aims were
twofold: 1) to evaluate the effectiveness of the In-MMPM program
regarding the reduction of stress, anxiety, depression, increased control,
global activity and life satisfaction and 2) to monitoring changing in biological stress markers. This naturalistic study was accepted by the local
ethic committee.
Method: Altogether, 102/116 patients (26 male/76 female) mean age
4611 years, mean duration of pain 158 years, mean pain intensity
(VAS) 6725 mm. Standardized self-assessment tools: Multidimensional
Pain Inventory (MPI), Hospital Anxiety and Depression (HAD) scale, Pain
intensity (VAS), Life satisfaction (LISAT-11) as well as morning saliva cortisol, serum- dehydroepiandrosterone (DHEA) and pancreas polypeptide
(PP) were collected at the beginning and end of the program. Paired sample t-test was used to compare the pre- and post treatment data.
Statistical significance level p<0.01.
Results: Patients were grouped by pathologically low level of salivary cortisol at 07:30 or serum PP (group 1) versus normal values (group 2).
Significant different bio-psychosocial profiles in both groups were found.
Group 1: DHEA, PP, HAD: Anxiety, MPI: Control of pain, Social activities, Global activity index, Life Satisfaction: Life as whole, Family
life. Group 2: HAD: Depression; MPI: Affective distress, Interference,
Control of pain, Global activity index, Social activities, Pain intensity;
Life Satisfaction: Psychosocial health, Physical health.
Conclusion: The results indicate two different bio-psychosocial profiles of
clinical outcome after the In-MMPM program. Patients with low cortisol
or PP values decreased in Anxiety score, DHEA and increase values of PP,
Control of pain, Social activities and Global activity index, Life as whole
and Family life scores. Patients with normal cortisol and PP values
decreased in Depression score, Affective distress, and increase in Control
of pain, Global activity index, Social activities, Psychosocial and Physical
health scores. These finding if repeated have highly clinical relevance.
116
P-23-01
Dopamine-beta-hydroxylase (DBH) activity and -1021C/T
polymorphism of DBH gene in posttraumatic stress disorder
Dorotea Muck-Seler
R.Boskovic Institute, Division of Molecular Medicine, Zagreb, Croatia
Maja Mustapic, Nela Pivac, Dragica Kozaric-Kovacic, Martina Dezeljin
Introduction: Posttraumatic stress disorder (PTSD) is complex and polygenic disorder. The etiology of PTSP is unclear. It could be related to the
changes in catecholaminergic system, including altered activity of
dopamine beta-hydroxylase (DBH), an enzyme that metabolizes
dopamine (DA) to noradrenalin (NA). The aim of the present study was to
determine the association between plasma DH activity and -1021C/T
polymorphism of DBH gene in war veterans with or without PTSD.
Method: Plasma DBH activity and DBH-1021C/T polymorphisms were
determined in 133 combat veterans with current and chronic PTSD (subdivided further into two subgroups according to the presence or absence
of psychotic features) and in 34 veterans without chronic PTSD. PTSD
diagnosis was done using the Structured Clinical Interview (SCID) for
DSM-IV. Plasma DBH activity was determined by a photometric method.
Genotyping was performed using standard RFLP technique.
Results: A significantly lower plasma DBH activity was found in veterans
with PTSD, regardless of the presence of psychotic features, as compared
to enzyme activity in war veterans without PTSD. Similar frequencies in
genotype or allele distribution were found between veterans with or
without PTSD. War veterans with PTSD carrying the CC genotype had significantly lower plasma DBH activity than veterans without PTSD carrying
the corresponding genotype.
Conclusion: The results suggest that genotype-controlled measurement
of plasma DBH activity might be used as a potential biological marker of
the response to trauma and that the further studies of DBH and other loci
related to DA and NA in PTSD are warranted.
P-23-02
Trauma and Coping
David Vyssoki
ESRA, Vienna, Austria
The surviving victims of the holocaust are, on the one hand, complex and
highly traumatized, and on the other hand, they demonstrate an incredible will to survive. Within this range, there are many possibilities for psychosocial care, psychotherapeutic work and psychiatric treatment to
make helpful offers and to support the permanent coping demands.
Using Esra (Outpatient clinic for long-term consequences of holocaust
and migration syndromes) as an example, it will be shown what models
and possibilities exist in relation to this support. The issues of barriers in
access, limitations in treatment possibilities and best practice models will
be addressed. The theoretical background for understanding this specific
form of traumatisation is provided by the model of Hans Keilson, who
classifies tramatisation into three phases: the phase before traumatisation, the phase during the traumatisation and the phase following it. These
three phases hold the specific factors that bestow a specific dynamic to
the dynamic of psychical damage and the related coping demands. These
are captured in the practical work and integrated into the respective therapeutic processes.
Esra works with a multifactorial trauma coping model, which incorporates
elements of social work, nursing, psychotherapy, psychiatry and internal
medicine. By means of case studies and therapy progress studies, the integration of these elements will be elucidated and the role of psychiatry will
be reflected.
Esras treatment model, based on the multiphasic traumatisation model of
Hans Keilsen, will be reflected in relation to its transferability to other victim groups.
ANXIETY - Poster
P-23-03
Qualitative study on the therapeutic effects of SSRI in
patients with PTSD
Pedro Rosa
FMUSP, Anxiety Clinic (AMBAN) IPq, Sao Paulo, Brazil
Felipe Corchs, Fabio Corregiari, Marcio Bernik
Introduction: The present study describes the therapeutic effects of serotonin reuptake inhibitors (SSRI) in patients with Posttraumatic Stress
Disorder (PTSD). The main objective was to develop a more qualitative
and sophisticated evaluation of this medication in patients that achieved
full remission.
Method: Five patients (3 female and 2 male; mean age 26,46,42) with
PTSD according to the Mini-International Neuropsychiatric Interview
(M.I.N.I.; DSM-IV) all of them also had major depressive disorder and two
had Generalized Anxiety Disorder. They were evaluated before and after
the treatment with the Hamilton Depression Rating Scale (HAM-D), the
Profile of Mood States (POMS), the Beck Depression Inventory (BDI), the
Spilberger State-Trait Anxiety Inventory (STAI) and the Davidson Trauma
Scale (DTS).
Results: The applied scales shown a great reduction of symptoms: HAMD from 29;85,06 to 21,22; BDI from 39,27,88 to 5,21,48; and STAI
from 696,16 to 37,63,91. The DTS scale demonstrated improvement
in all typical PTSD clusters of symptoms as discussed in the poster. The
POMS scale demonstrated a very important improvement in all tested factors and the total distress reduction at POMS was from 142,45,36 to
11,823,66. Detailed descriptions of DTS and POMS are qualitatively
exposed and discussed.
Conclusion: These findings are in accordance with the literature that
SSRIs are affective in all PTSD clusters of symptoms as though as in associated manifestations such as depressed mood.
P-23-04
Alteration of serotonin-1A receptor binding potential in
the limbic system after SSRI treatment in male patients
with anxiety disorder
Christoph Spindelegger
Rupert Lanzenberger, Markus Mitterhauser, Leonhard Key Mien, Patrycja
Stein, Wolfgang Wadsak, Ulrike Moser, Alexander Holik, Kurt Kletter,
Siegfried Kasper
Introduction: The serotonin-1A (5-HT1A) receptor regulates serotonergic
firing in the raphe nuclei and serotonergic inhibition of GABAergic and
glutaminergic neurons. Altered 5-HT1A receptor binding potentials (RBPs)
were found in patients suffering from anxiety disorders (AD). Selective
serotonin reuptake inhibitor (SSRI) treatment raises the serotonin level in
the synaptic cleft and might change postsynaptic receptor densities.
Therefore, our study aimed at investigating the effects of long-term treatment with escitalopram on the 5-HT1A RBP in patients suffering from AD.
Method: 12 male (30.65.9 years) outpatients suffering from AD were
measured with PET. Two dynamic scans were performed (one prior to and
one after 12 weeks of escitalopram treatment). Scans started simultaneously with a bolus injection of [carbonyl-11C]WAY-100635 (average dose
383.033.0 MBq). 30 time frames (15*1min, 15*5min) led to a total
acquisition time of 90 minutes. 8 regions of interest (ROI) were defined a
priori and delineated on the co-registered MR images (orbitofrontal cortex,
amygdala, hippocampus, subgenual cortex, anterior and posterior cingulate cortex, dorsal raphe nucleus, cerebellum as reference region). The
quantification of 5-HT1A RBP was performed using the Simplified
Reference Tissue Model. Paired samples t-tests between both scans were
done by means of SPSS.
Results: We found a significant reduction of the 5-HT1A RBP after 12
weeks escitalopram treatment in hippocampus (p=0.006), subgenual cortex (p=0.017) and posterior cingulate cortex (p=0.034). The significance
of the hippocampus region survived the Bonferroni-adjusted threshold for
multiple comparisons.
Conclusion: To our knowledge, this is the first PET study reporting a significant decrease in 5-HT1A RBP after SSRI treatment of patients with anxiety disorders. These data complement the results of Meyer et al.(1), who
found decreased binding of 5-HT2A, the major excitatory serotonergic
receptor, after 6 weeks treatment with paroxetine in patients with depression.
References: 1: Meyer, J. H., Kapur, S., Eisfeld, B., Brown, G. M., Houle,
S., DaSilva, J., Wilson, A. A., Rafi-Tari, S., Mayberg, H. S. and Kennedy,
S. H. (2001) Am J Psychiatry, 158, 78-85.
P-23-05
Efficacy of sertraline in the treatment of post traumatic
stress disorder
Alma Dzubur Kulenovic
University Medical Center, Sarajevo, Bosnia and Herzegovina
Alma Bravo-Mehmedbasic, Abdulah Kucukalic
Introduction: To determine the efficacy of sertraline in the treatment of
Post Traumatic Stress Disorder.
Method: The sample consisted of 30 patients with symptoms of chronic
Post Traumatic Stress Disorder. All subjects received treatment with sertraline in therapeutic dose range in the period of three months. All subjects
were assessed prior to treatment and in 1 month-follow-up and 3 months
follow-up using of following instruments: Mississippi Questionnaire for
PTSD, The Clinical Global Impressions scale (CGI), and the Hamilton
Depression rating scale (HAM-D-21).
Results: The difference between three assessments with Mississippi
Questionnaire for PTSD was statistically significant. PTSD rate in our sample
was reduced from 100% prior to treatment to 64% subsequent to treatment with sertraline. The results indicate statistically significant reduction
of depression on the Hamilton Depression rating scale (HAM-D-21), following three months treatment with Sertraline. The difference between
three assessments with The Clinical Global Impressions scale was statistically significant. Sertraline was administered in daily dosis of 50 mg in
88% of the subjects, and in the daily dosis of 100 mg in the remaining
12% of the subjects. Unwanted effects were registered in two of the subjects and they were of mild intensity.
Conclusion: Sertraline proved to be very efficient in treatment of symptoms of Post Traumatic Stress Disorder for the subjects in this study.
Sertraline is efficacious, well tolerated and safe psychopharmacological
agent for the treatment of PTSD.
References: 1. Montgomery S: The selective serotonin reuptake
inhibitors. Clinical Neuropharmacology 1992; 15 (Suppl A):353 A-354 A.
2. Southwick SM, Krystal JH, Bremner JD et al, Noradrenergic and serotonergic function in posttraumatic stress disorder, Arch Gen Psychiatry (1997)
54: 749-58.
P-23-06
Behavioral phenotyping of transgenic rats in the canopy
test
Jrg-Peter Voigt
University of Nottingham, School of Veterinary Medicine, Sutton
Bonington, United Kingdom
Andre Rex, Michael Bader, Heidrun Fink
Introduction: The transgenic rat TGR(ASrAOGEN)680, characterized by a
transgene producing antisense RNA against angiotensinogen in the brain,
provides an opportunity to study behavioral effects of angiotensin. In a
previous study, we obtained evidence for an anxious phenotype in this
rat. The present study was aimed at further extending the phenotyping of
this rat by using a new test of anxiety-related behavior.
Method: Behavior was studied in the recently developed canopy test that
makes use of the behavioral element stretched attend posture (SAP). SAP
is an important component of the risk-assessment repertoire of defensive
behavior in rodents. The SAP test apparatus comprised an elevated circular platform. A smaller clear circular canopy was supported directly
above the platform by a central pillar, thus dividing the platform into an
inner and an outer exposed zone.
117
ANXIETY- Poster
Results: Vehicle treated transgenic rats and wild-type Sprague Dawley

(SD) rats spent about the same time in the covered zone. This time was
significantly reduced after administering 0.5 mg/kg diazepam. However,
the transgenic rats showed a significantly higher incidence of risk assessment when compared to SD rats, indicating an increased level of anxiety
in these rats. The anxiolytic dose of diazepam required to reduce the frequency of SAP was higher in the transgenics (0.25 mg/kg) as compared
to SD (0.125 mg/kg).
Conclusion: These data suggest that the canopy SAP test is a useful paradigm to investigate risk assessment behavior in transgenic rats. The test
could provide an additional useful model for phenotyping transgenic
rodents.
Rerences: Grewal SS, Shepherd JK, Bill DJ, Fletcher A, Dourish CT.
Behavioural and pharmacological characterisation of the canopy
stretched attend posture test as a model of anxiety in mice and rats.
Psychopharmacology (Berl). 1997 133: 29-38
P-23-07
Comparison of pharmacotherapy and psychotherapy effectiveness on brain neuroplasticity in patients suffering from
anxiety disorders
Maciej Matuszczyk
Department of Psychiatry, Katowice, Poland
Irena Krupka-Matuszczyk, Adam Klasik, Jacek Przybylo, Zdzislawa Pilarz
Introduction: The aim of the study was to evaluate the effectiveness of
different forms of therapeutic methods on cognitive functions improvement.
Method: Their effectiveness was assessed with the Vienna Test System
(VTS). The study covered patients treated at the Psychiatry and
Psychotherapy Clinic of the Medical University of Silesia in Katowice,
Poland. Participation in the study was restricted to individuals with a diagnosis of an anxiety disorder (acc. to ICD-10: F-40-F48 excl. F42).
60 patients participated in the study. They were divided into 3 groups
treated with pharmacotherapy, psychotherapy or both, respectively.
Results: Results: Cognitive functions improvement was found to be correlated with the intensification of the initial disorder.
Conclusion: An improvement in concentration and attention was present
on average after 6-8 weeks of treatment and was most prominent in
patients treated with both forms of therapy.
References: 1. Black D.W.: Efficacy of combined pharmacotherapy and
psychotherapy versus monotherapy in the treatment of anxiety disorders.
CNS Spectr. 2006 Oct;11(10 Suppl 12):29-33. 2. Linden D.E.: How psychotherapy changes the brainthe contribution of functional neuroimaging. Mol Psychiatry. 2006 Jun;11(6):528-38.
P-23-08
A comparison of neuropsychological functioning in traumatized adolescents with and without post traumatic
stress disorder
Renata Schoeman
University of Stellenbosch, Psychiatry, Cape Town, South Africa
T. Middleton, I. Jordaan, Paul Carey, Soraya Seedat
Introduction: Childhood abuse and resultant PTSD have been associated
with cognitive developmental impairments, e.g. intellectual and emotional developmental delays and language and psychomotor
deficiencies.This study aimed to assess the impact of trauma and PTSD on
various neurocognitive functions. We hypothesized that traumatised adolescents with PTSD will demonstrate significantly more impairments in
cognition related to attention, memory, and frontal lobe functions than
those without PTSD.
Method: 40 consecutively referred traumatized adolescents to the
Bathuthuzele Youth Stress Clinic, were evaluated for the presence/absence
of PTSD using a structured diagnostic interview and were then referred
for neuropsychological evaluation using a standardized neuropsychological
test battery. Data were analysed using SPSS 14.0 for Windows. Groups
with and without PTSD were compared using student t-tests for numerical
variables and chi-square tests for categorical variables.
118
Results: The PTSD and control groups were similar on all demographic
variables. No significant cognitive differences were found, however the
PTSD group showed a trend towards greater impairment in verbal memory,
as well delayed recall in visual memory. There also seemed to be a trend
towards more interference in recall in the PTSD subjects as well as impairment in recognition memory.
Conclusion: These findings suggest that patients with PTSD experience
cognitive problems, specifically related to verbal memory. Determining
cognitive deficits related to attention, verbal and visuo-spatial memory in
trauma-exposed adolescents may lead to a better understanding of the
impairment and disability associated with PTSD, and may guide more
appropriate intervention strategies.
References: Barrett, D.H., Green, M.L., Moris, R., Gilehs, W.H., & Croft,
J.B. (1996). Cognitive functioning and Posttraumatic Stress Disorder.
American Journal of Psychiatry, 153(11), 1492-1494. Bremner, J.D.,
Scott, T.M., Delaney, R.C., Southwick, S.M., Mason, J.W., Johnson, D.R.,
Innis, R.B., McCarthy, G., & Charney, D.S. (1993). Deficits in short-term
memory in Posttraumatic Stress Disorder. American Journal of Psychiatry,
150(7), 1015-1019. Moradi, R., Doost, H.T.N., Taghavi, M.R., Yule, W., &
Dalgleish, T. (1999). Everyday memory deficits in children and adolescents
with PTSD: Performance on the Rivermead Behavioural Memory Test.
Journal of Child Psychology, 40(3), 357-361. Yehuda, R., Keefe, R.S.E.,
Harvey, P.D., Levengood, R.A., Gerber, D.K., Geni, J., & Siever, L.J. (1995).
Learning nd memory in combat veterans with Posttraumatic Stress
Disorder. American Journal of Psychiatry, 152(1), 137-139.
P-23-09
Personality dimensions, approach-avoidance behavior and
serotonergic neurotransmission in patients with anxiety
disorders and Borderline Personality disorder
Andreas Thum
University Clinic of Marburg, Clinic of Psychiatry, Germany
Beate Nekwasil, Thomas Schneyer, Thomas Wfibbena, Marco Giesler,
Mathias Bender, Jrgen-Christian Krieg, Ulrich Hemmeter
Introduction: Patients with Borderline Personality disorder (BPD) and
patients with anxiety disorders (AD) clearly contrast in personality traits
(predominantly traits related to the impulsivity / aggression spectrum), in
behavior (avoidance vs. impulsive (approach) behavior) and in neurobiological reactivity upon serotonergic stimulation. According to Gray (1973)
impulsivity and anxiety are independent personality traits which are characterized by a different susceptibility for stimuli of reward and punishment. Furthermore, these two dimensions of personality differ in serotonergic reactivity.
Method: Therefore, a study in patients with BPD and AD, which includes
the parallel assessment of personality, behavioral performance and neuroendocrine responsiveness to a serotonergic stimulation has been conducted. 15 patients with BPD and 15 patients with AD have been examined. All patients had to complete personality questionnaires, such as
I7, BIS 11 (impulsivity), STAI, anxiety related traits of NEO FFI and TCI. In
addition, all patients underwent an approach-avoidance paradigm in
which reward and punishment were systematically varied. Furthermore, a
serotonergic stimulation test (oral application of citalopram 20 mg vs.
placebo) with the assessment of cortisol and prolactin was performed in
the afternoon in both groups.
Results: The results show that cortisol stimulation by citalopram significantly differs between groups, showing a more pronounced cortisol rise
in BPD than in AD after citalopram. In addition, prolactin increased after
citalopram in BPD, but not in AD. The behavioural approach-avoidance
paradigm showed a significant better performance only in the condition,
in which reward could be easily achieved for the BPD group compared to
AD. No differences between groups were found in the difficult reward
condition and the conditions of punishment. Furthermore, citalopram
induced cortisol-secretion was significantly related to performance in the
reward condition.
Conclusion: These results show that patients with AD und BPD did not
only differ in distinct dimensions of personality, such as traits of impulsivity, they also show a different serotonergic neurotransmission reflected by
differences in cortisol and prolactin secretion to citalopram stimulation.
Furthermore, the data suggest that the observed difference in serotonergic
neurotransmission may be related to the difference in personality traits
and behavioural performance between both groups of patients.
ANXIETY- Poster
P-23-10
Stress related disorders: The transnosografic dimension
Mario Catena
Psychiatry, Neurobiology, Pisa, Italy
Sivia Gorini Amedei, Franceso Rotella, Luca Faravelli, Rosemma Paggini,
Agnese Palla, Alessandra Scarpato, Michela Picchietti, Giovanni Ciampa,
Giorgio Consoli, Carlo Faravelli
Introduction: Life events have long been associated with the onset of
mental disorders. Hypothalamic-pituitary-adrenal (HPA) axis function, in
turn, has been reported to be abnormal in almost all psychiatric disorders,
particularly in depression. The aims of the study were to test the hypothesis
that HPA axis dysfunction is present in various psychiatric disorders and
not only in depression, and to evaluate if the HPA axis dysfunction is associated to specific symptoms and to life events exposure.
Method: The dexamethasone (dex) suppression test was made in order
to identify HPA axis dysfunctions: dex was administered at 11 p.m. of the
1st day, while salivary cortisol samples, basal (8 a.m. and 8 p.m. of the
1st day) and after dex administration (8 a.m. of the 2nd day), were taken
in 73 patients with at least one DSM-IV axis I diagnoses (SCID-I) and in
23 control subjects. The ability of glucocorticoids (dex) to suppress the
HPA axis (suppression index, IS) was measured by using the ratio between
cortisol levels after and before dex administration The Florence Psychiatric
Interview (FPI) was used in order to evaluate the symptoms of the current
episode, life events and patientss socio-demographic characteristics.
Results: A significant higher basal cortisol level (6.0 3.7 vs 3.9 1.7,
p<.05) was found in the patient group compared to controls at 8 p.m.
After dex administration, patients showed significantly higher cortisol
levels than controls (7.9 6.5 vs 4.1 2.7, p<.05). The IS was lower in
control subjects than in patients (0.26 0.14 vs 0.47 0.29, p<.05),
while indicating that these latters are characterized by a reduction of the
ability of glucocorticoids to suppress the HPA axis. Amongst patients, the
condition of non suppression was associated to specific symptoms irrespective of the diagnosis, such as depressed mood, anhedonia, low selfesteem and energy, indecision, low affectivity, lack of concentration and
panic attacks.
Conclusion: HPA dysfunction seems to characterize patients irrespective
of the diagnosis and to be associated to a specific symptoms pattern. No
relation between life events and HPA disfunction was found.
References: Pariante CM, Miller AH. Glucocorticoid receptors in major
depression: relevance to pathophysiology and treatment. Biol Psychiatry
2001 Mar 1;49(5):391-404.
P-23-11
Evaluacion costo efectividad de un tratamiento protocolizado en mujeres con depresion severa y antecedentes de
trauma infanto-juvenil consultantes a un servicio de salud
general
Veronica Vitriol
Soledad Ballesteros, Daniel Schwartz, Ramon Florenzano, Ignacio Iturria,
Carolina Nunez
Introduction: Los antecedentes de abuso fisico y sexual infantil, son
antecedentes frecuentes de encontrar en mujeres consultantes por
Depresion Severa en los Servicios de Salud. No existen intervenciones adecuadamente sistematizadas, evaluadas y desarrolladas en los servicios de
salud, que aborden al mismo los antecedentes traumaticos en mujeres
con depresion. El objetivo de esta comunicacion es comparar el costo
efectividad de un protocolo de tratamiento, de tres meses de duracion,
que relaciona el motivo de consulta actual con los antecedentes
traumticos infantiles como foco psicoterapeutico.
Method: Material y Metodo: 87 mujeres con Depresion severa segun CIE
10 con poli trauma infantil y/o abuso sexual, consultantes por primera vez
en Psiquiatria del Hospital de Curico, fueron randomizadas aleatoriamente a tratamiento protocolizado (TP) n 44, y tratamiento naturalostico ( TC) n 43. Evaluadas al inicio, mes, tercer y seis meses con el OQ-45,
validada en nuestro medio con criterios de recuperacion y mejoria. Se
determino el costo directo de cada tratamiento a traves de una planilla de
gastos El costo / efectividad se esta determinando dividiendo el total del
costo por tratamiento segun los valores del Servicio de Salud por el
numero de pacientes mejorados y recuperados por tratamiento segun

OQ45. Resultados preliminares primer mes.
Results: Numero pacientes recuperados y mejorados de tratamiento protocolizado segun OQ 45= 16, Total costo tratamiento $ 2.941.312,
Costo/ efectividad por paciente $ 183.832 por paciente. Numero
pacientes recuperados mas mejorados de tratamiento naturalistico= 13,
costo de tratamiento $ 3.585.168, costo/ efectividad $275.782 por
paciente. Promedio del numero de dias de hospitalizacion tratamiento
protocolizado 6,9; tratamiento naturalistico 19,6 .
Conclusion: Conclusiones. Al primer mes el tratamiento protocolizado
demuestra tener un menor costo y ser ms efectivo que el tratamiento
naturalistico, principalmente por evitar las hospitalizaciones prolongadas
Este resultado es preliminar se requieren las evaluaciones siguientes para
conclusiones mas definitivas asi como incluir en el analisis, los costos indirectos.
References: Solomon SD, Davidson JRT: Trauma: prevalence, impairment,
service use, and cost. Journal of Clinical Psychiatry 58(suppl 9):5-11, 1998
-RosembergS D, Muesser K T, Friedman M J, Gorman P G, Drake R E,
Vivader R M et al. Developing effective treatments for posttraumatic
stress disorders among people with severe mental illness. Psychiatr Serv
2001; 52(11):1453-61
P-23-12
Relacion trauma infantil a comorbilidad depresion con
trastorno posttraumatico
Veronica Vitriol
Soledad Ballesteros, Ana Calderon, Andrea Vacarezza, Ramon
Florenzano, Jessica Ubilla
Introduction: El TEPT (Trastorno por estres postraumitico) es una entidad
frecuente de encontrar en sujetos que presentan Depresion. Uno de los
factores de riesgo asociados en forma independiente a ambas enfermedades son los antecedentes de abuso fisico y sexual de la infancia. Este
trabajo tiene como objetivo: Determinar la frecuencia de Trastorno por
Estres Postraumtico en mujeres con Depresion Severa, consultantes a un
Servicio de Salud General y estudiar la relacion entre los antecedentes de
politrauma infantil a la comorbilidad Depresion Severa- TEPT.
Method: Material y Metodo: Se compararon 87 mujeres con depresion
severa ( CIE 10 Hamilton > 21 puntos) y politrauma infantil ( tres o mas
antecedentes y/o contacto sexual forzado) con 36 mujeres con depresion
severa sin trauma infantil. En forma ciega al antecedente de politrauma
infantil se aplico CIDI para establecer diagnostico TEPT segun CIE 10.
Results: Resultados: 50,4% (62 pacientes) de la muestra total cumple
con los criterios para TEPT segun CIDI, 52,8 % de las con politrauma y
44,4 % de las sin trauma. Pacientes sin trauma infantil experimentaron,
en promedio 2,15 sucesos traumtico, las con politrauma infantil 3, 87 se
observan diferencias estadisticamente significativas entre ambos grupos
(t =5,014 y p =0,001). Pacientes con politrauma en un 41,3% el evento
mas traumatico en sus vidas, fue la violacion. Entre los pacientes sin trauma infantil, un 36,1% no manifiesta tener algun evento como el mas traumatico. Comparando las pacientes con politruama y sin trauma hay diferencias significativas en todas las respuestas del CIDI al evento traumatico.
Conclusion: Este estudio confirma en nuestro medio, la alta prevalencia
de TEPT en comorbilidad a Depresion Severa en mujeres consultantes a un
Servicio de Salud Mental. La prevalencia de TEPT en esta poblacion es
mucho mayor a lo encontrado en la poblacion general**
References: *-Oquendo M, Brent D, Birmaher B, Greenhill L, Kolko D,
Satnley D et al. Postraumatic stree disrorder comorbid Depression: Factors
Mediating the association with suicidal behavior. Am Jpsychiatry
Association 2005 162;560-66 **- Vicente B P, Rioseco P S, Saldivia S B,
Kohn R, Torres S P Estudio chileno de prevalencia de patologia psiquiatrica
(DSM-III-R/CIDI) (ECPP) Rev.Med.Chile v.130 n.5 Santiago mayo 2002
119
ANXIETY - Poster
P-23-13
Relationship between child trauma and comorbility depression with traumatic stress disorder
Veronica Vitriol
Soledad Ballesteros, Ignacio Iturria, Ramon Florenzano, Kristina Weil,
Ana Calderon
Introduction: PTSD is disorder found frequently in subject with depression. One of the risk factor associated independent in both diseases are a
part history of Physical or sexual abuse in childhood. Objective:
Determine the frequency of PTSD in women with severe depressive
attending a primary care facility and study the relation between multiple
child trauma or abuse and comorbility of severe Depression and PTSD.
Method: Methods: 87 women with severe depression ICD-10 rated with
Hamilton-21 and multiple child trauma (three or more incident or sexual
abuse) were compare with 36 women with severe depression without
childhood trauma. CIDI was applied blindly in reference to childhood
trauma to establish the diagnosis of PTSD according to ICD10.
Results: Result: 50.4% of the total sample satisfied the criteria for PTSD.
52.8% of them with childhood trauma and 44.4% without trauma.
Patients without childhood trauma had and average of 2.15 traumatic
incidents and the once with childhood trauma 3.87 incidents (t=5.014 ,
p=0.0001). 41.3% of patients with politrauma had been raped.
Comparing patients with and without trauma there were significant differences en CIDI and traumatic events.
Conclusion: Conclusion: The study confirms a high prevalence of PTSD in
comorbility with severe depression compared to the general population
(5.4% Vicente 2002).
References: -Oquendo M, Brent D, Birmaher B, Greenhill L, Kolko D,
Satnley D et al. Postraumatic stress disrorder comorbid Depression:
Factors Mediating the association with Suicidal Behavior. Am J Psychiatry
2005 162;560-66 - Vicente B P, Rioseco P S, Saldivia S B, Kohn R, Torres
S P Estudio chileno de prevalencia de patologia psiquiatrica (DSM-IIIR/CIDI) (ECPP) Rev.Med.Chile v.130 n.5 Santiago mayo 2002
120
CHILDHOOD & ADOLESCENT DISORDERS - Poster
P-24
Childhood & Adolescent Disorders
P-24-01
Mental health study in chilean schoolchildren I:
Prediction of behavioral problems
Flora de la Barra
Introduction: One of the issues of research in developmental psychopathology is the persistence of behavioral/emotional problems
throughout the life span. Early predictors of future problems can be
detected by longitudinal studies. In Latin America, no such studies have
been carried out before
Method: Two cohorts of first grade schoolers (N: 1279) were rated by
teachers and parents with instruments (TOCA-R and PSC) that were validated for chilean population. 535 of these children were followed up to
sixth grade and evaluated by the same instruments blind to the first grade
infiormation. Logistic regression models were created to identify predictors at first grade for the problems found in sixth grade.
Results: Teachers reported more problems than parents in first grade
:(33.3% vs. 10.5%) and in sixth grade (35.5% vs.5,9% ). Results showed
persistence of teacher reported disobedience/aggression, shyness, hyperactivity and parent rated behavioral problems. Prediction was found within and across disruptive behaviors as well as between cognitive and
behavioral problems.
Conclusion: In this study it was possible to detect early behavioral/emotional problems in children and their continuity along six years follow up.
It provides oportunity for implementing preventive intervention programs
in the school setting
References: de la Barra F, Toledo V, Rodriguez J. J. Child Psychiatry and
Human development, vol 35(3), Spring 2005, 227-243.
Method: A representative sample was extracted from a population of six

graders, considering the parents and teachersscores of behavioral problems (N-210). Guidelines for a semistructed clinical interview and mental
health examinarion were developed. Third year psychiatric fellows trained
in the use of ICD-10 performed psychiatric evaluation of all diagnoses in
the six axes.
Results: Overall prevalence was 45,7%, which was reduced to 15,7%
when adjusted for disability. Emotional disorders were the most prevalent,
followed by depressive and conduct disorders. Comorbidity was found in
20,8% of the complete sample and in 39,8 % of the children with disability(P= o.oo6). Disability was associated with 100% depressive disorders, 75% of mixed conduct/depression, 44,1% of ananxious/emotional,
31,3% of conduct and 28,6% of conduct/emotional disorders. All the
impaired children suffered from abnormal psychosocial situations (Axis V)
Conclusion: Adjusted prevalence is comparable to studies in developed
countries. The type of Axis one diagnosis, comorbidity and psychosocial
abnormal situations contributed to impairment. ICD-10 syndromatic diagnoses (Axis I) are overinclusive, consideration of impairment reduces
prevalence to the more severe cases. Assesment of the 6 axes helps evaluation of the complexity of child and adolescent psychopathology. This
comprehensive information can help the implementation of guidelines for
referral of children to specialized services.
References: de la Barra F, Toledo V, Rodriguez J. Mental health study in
two cohorts of schoolchildren from West Santiago: psychiatric disoreders,
psychosocial diagnosis and imparment. Rev. Chil. Neuropsiquiat 2004;
42(4): 259-272.
P-24-03
Parenting trends and associated risk for mental disorders
among progenies during adult hood- Malaysian mental
health study (MMHS)
Kavitha Subramaniam
Penang Medical College, Dept. Public Health Medicine, Malaysia
Saroja Krishnaswamy, Tishya Indran, Abdul Aziz Jemain, Abdul Hamid
P-24-02
Mental health study in chilean schoolchildren II: Psychiatric
disorders, psychosocial diagnosis and disability
Flora de la Barra
Virginia Toledo
Introduction: Prevalence and types of psychiatric disorders in general
child and adolescent population have been measured in many countries,
but not in Latin America. Rates are similar for studies that considere
impairment criteria. ICD-10 is the official classification of psychiatric disorders used by the chilean Health Ministery. It is important for countries
to consider epidemiological studies when making treatment plans.
Introduction: Previous findings from MMH study had suggested the

presence of correlation between delayed parenting and risk for Common
Mental Disorders (CMD). Children born for fathers aged 50 and above
were found to be 3.50 times more likely to develop CMD during adulthood than those born to fathers in their twenties. Delayed parenting
could be considered a recent trend and therefore could probably place
the younger generation in a more vulnerable situation to mental disorders. Objective: This study aims to discuss the changes in parenting trends
in the Malaysian population and parental age related risk for CMD among
different age groups.
Method: MMHS Subjects who could remember at least one parents age
at birth were selected. Descriptive statistics were used to study trends in
parenting. Logistic regression model was developed to identify groups
that have high risks for CMD.
121
Results: Peaks in paternal age at birth showed a transition from 20-29

among subjects age of 30 and above to 30-39 among the teenagers
(16-19). Subjects in twenties showed almost similar percentages for
fathers in 20s and 30s. No significant increase was observed in the rates
of paternal age of 50 and above among the younger generation. Having
an old father was a risk for mental health among subjects aged 40-49
(OR =8.734, p=0.013). Younger subjects aged 16-29, who were born for
teenage fathers had elevated risk for mental illness (OR=15.287,
p=0.001). Maternal age profiling showed that teenagers had high percentage of mothers in 30s and 40s than others. Maternal age failed to
show significant impact in the model.
Conclusion: There is a change in parenting trends in the population.
Parental age associated risk for mental illness varied across the age
groups. Delayed parenting is not the major risk for CMD among the younger
generation in the sample population.
P-24-04
Nocturnal polysomnographic study in a childrens sample
with Attention Deficit Hyperactivity Disorder, with hyperactivity-impulsivity-type
Yulizen Alfonso
Neurociences Center of Cuba, Neurophysiology, Havana, Cuba
Introduction: Children with ADHD can present a high prevalence rate of
comorbidity with sleep disorders. The exact nature of these sleep problems are still to be determined. Objectives: To describe the sleep disorders found by nocturnal polysomnographic study (PSG) in a sample of
10 children with diagnosis of ADHD with hyperactivity-impulsivity-type
Method: We studied 10 children (1 female and 9 males) with a mean age
of 9,30 (SD: 4,498148) who met DSM-IV criteria of (ADHD) with hyperactivity-impulsivity-type ADHD (ADHD/H). They were evaluated by a nocturnal polysomnographic study and neurological exploration.
Results: All studies were abnormal, 7 (70%) of the children presented
period movements legs syndrome (PMLS). The sleep architecture of
8 (80%) children with ADHD shows an increase in the percentage of
phase III and consequently decreases of phase II of slow sleep. The REM
latencies was increased in 7 (70%) of the studied children, whereas the
REM percentage was diminished in 5 (50%). Epileptiform-type paroxysms
were observed in 40% of the children who presented symptoms of
ADHD/H and in 4 of all sample`s declarations of parasomnias were
demonstrated.
Conclusion: The increase in phase III may be related to the alterations in
noradrenaline and dopamine transmission present in children who suffer
from ADHD. Some children with ADHD can have a region of the brain
with intense epileptic activity, which does not trigger epileptic seizures but
gives rise to behavioural disorders.
References: -American Sleep Disorders Association. Recording and scoring leg movements. The Atlas Task Force. Sleep 1993;16:748-59. Zucconi, M.; Ferri, R. et al. The official World Association of Sleep
Medicine (WASM) standards for recording and scoring periodic leg movements in sleep (PLMS) and wakefulness (PLMW) developed in collaboration
with a task force from the International Restless Legs Syndrome Study
Group (IRLSSG). Sleep Medicine 7 (2006) 175-183
P-24-05
Does smoking in teenagers affect their everyday
prospective memory performance?
T. S. O'Neill
Northumbria University, Division of Psychology, Newcastle-Upon-Tyne,
United Kingdom
Thomas Heffernan, J. Bartholomew
Introduction: This study was designed to assess what impact long-term
smoking has upon everyday prospective memory (PM) in teenagers.
Heffernan et al., (2005) found that older smokers reported a greater
number of long-term PM errors than non-smokers on the self-reported
Prospective Memory Questionnaire (PMQ). The present study aims to
extend this research to focus on a teenage cohort and to extend the
research paradigm to include the PMQ and an objective measure of PM.
Methods: A non-experimental design was used. Thirty-eight smokers and
122
38 non-smokers were tested, all of whom were college/university students studying in the North-East of England. Each participant was asked
to complete the PMQ - a self-rating scale used to gauge the number of
errors in short-term, long-term, and internally-cued aspects of everyday
PM, as well as the number of strategies used to aid memory, and a videobased prospective memory task during which the person has to remember particular activities at particular locations as they appear on the video.
A drug-use questionnaire determined how many cigarettes were smoked
per week, as well as other drug use.
Results: A series of one-way ANOVAs revealed that the smokers were
older, drank more alcohol and used more cannabis, than the non-smokers, with no difference on strategy use. A MANCOVA revealed that, after
controlling for age, alcohol use and cannabis use, the smokers reported
more lapses in their long-term PM and recalled less on the video-based
PM task, than the non-smokers.
Conclusion: Self-reported and objective deficits in everyday PM are associated with smoking in teenagers.
References: Heffernan, TM., Ling, J., Parrott, AC., Buchanan, T., Scholey,
AB., & Rodgers, J.(2005). Self-rated everyday and prospective memory
abilities of cigarette smokers and non-smokers: A web-based study. Drug
and Alcohol Dependence, 78, 235-241.
P-24-06
Validation of the center for epidemiological studiesdepression (ces-d) scale for the screening of depressive
symptoms in adolescents from Bucaramanga, Colombia
Paul Anthony Camacho Lopez
UNAB, Santander, Bucaramanga, Colombia
German Eduardo Rueda Jaimes, Jose Fidel Latorre Latorre, Alvaro Andres
Navarro Mancilla, Mauricio Escobar Sanchez, Jorge Augusto Franco
Lopez
Introduction: In Colombia, the lifetime prevalence of depression in adolescents for 1997 was of 13.3% and 20.1% of 12 to 15 and 16 to 19
years old, respectively.(1,2) The objective of this study was to determine
the criterion validity of the Center for Epidemiological Studies-Depression
Scale (CES-D) in students adolescents, for the screening of depressive
symptoms.
Method: A validation study with a cross-sectional sampling was design.
3468 eligible adolescents from nine schools in Bucaramanga (Colombia)
were evaluated both with CES-D and with the semi-structure clinical
interview for Diagnostic and Statistical Manual of Mental Disorders,
Fourth Edition (SCID-I) independently and blindly. A statistical analysis
was made considering the conditional probabilities through of tetracoric
tables to determine the predicting diagnoses from CES-D.(3)
Results: A total of 390 adolescents were surveyed. The mean age of the
population was 14,77 1,22 years and 44,36% were men. The prevalence of major depression episode based on the SCID-I was 11,54% [CI
95%: 8,62% - 11,23%]. The sensitivity was 73,33% [IC95%:57,79% 84,9%], specificity 73,62% [IC95%: 68.58% - 77,13%], positive predict
value 26,61% [IC95%: 19,27% - 35,44%], negative predict value
95,49% [IC95%: 92,05% - 97,54%] and the area under ROC curve was
0,815 [CI 95%: 0,748 0,881] for a cutpoint equal or higher than twenty three in the score of CES-D. The ROC curve did not show a significant
difference analyzing by sex, but a significant difference was observed in
the analysis by scholar level (p=0.039) with a major discriminative capacity
in the primary scholar levels.
Conclusion: CES-D is a useful scale for the screening of depressive symptoms in Colombian adolescent students, with an adequate sensitivity and
specificity. However, the sensitivity and specificity varies with the populations scholar level.
References: 1. Torres de Glvez Y, Montoya I. Segunda Encuesta Nacional
de Salud Mental y Consumo de Sustancias Psicoactivas, Colombia, 1997.
Santa fe de Bogot: Ministerio de Salud, 1997. 2. Posada-Villa J, AguilarGayola S, Magana C, Gomez L. Prevalencia de trastornos mentales y uso
de servicios: resultados preliminares del estudio nacional de salud mental,
Colombia. 2003. Revista Colombiana de Psiquiatria 2004; 33(3):241-26 3.
Kraemer H. Evaluating medical test: Objective and Quantitative
Guidelines. California: Sage Publications, 1992.
P-24-07
Sounding out ADHD
Mary-Claire Hanlon
The University of Newcastle, CBMHR, Australia
Ulrich Schall
Introduction: Prepulse inhibition (PPI) of the acoustic startle response has
been used in research to index sensorimotor gating. Reduced PPI reflects
disrupted sensorimotor gating and may indicate dopaminergic dysfunction.
Method: The role of dopamine in sensorimotor gating was investigated
using attentional modulation of PPI of the acoustic startle response.
Intervals of 30ms, 60ms, 120ms, 240ms and 480ms divided a weak prepulse from a sudden loud startle. 30 participants aged between 16 and
28 years (12 diagnosed with ADD or ADHD) participated.
Results: All healthy controls took part in two testing sessions where electroencephalographic and electromyographic recordings showed attentional modulation of PPI at intervals of 120ms and 240ms. The ADD and
ADHD participants showed disrupted sensorimotor gating reflected in differentially modulated PPI. Medication (dextroamphetamine or
methylphenidate hydrochloride) also differentially modulated PPI in
ADD/ADHD participants in passive and active (attentional) conditions.
Conclusion: Stimulant medications may only be as useful as the motivation behind the need to perform a task. If the task is salient, the medication will be more effective.
References: Castellanos, F. X., Fine, E. J., Kaysen, D., Marsh, W. L.,
Rapoport, J. L., & Hallett, M. (1996). Sensorimotor gating in boys with
Tourettes syndrome and ADHD: Preliminary results. Biological Psychiatry,
39(1), 33-41. Hawk, L. W., Yartz, A. R., Pelham, W. E., & Lock, T. M.
(2003). The effects of methylphenidate on prepulse inhibition during
attended and ignored prestimuli among boys with attention-deficit hyperactivity disorder. Psychopharmacology, 165(2), 118-127. Ornitz, E. M.,
Russell, A. T., Hanna, G. L., Gabikian, P., Gehricke, J. G., Song, D., et al.
(1999). Prepulse inhibition of startle and the neurobiology of primary nocturnal enuresis. Biological Psychiatry, 45(11), 1455-1466.
P-24-08
Childhood social adversities in adults with Attention
Deficit Hyperactivity Disorder (ADHD)
Vanessa de Almeida Silva
Inst. de Psiquiatria d Hosp., Fac. de Medic. d. Univ., Sao Paulo, Brazil
Mario Louz
Introduction: Attention-deficit hyperactivity disorder (ADHD) in adults is
a common and under diagnosed condition. Without proper treatment,
ADHD continues to produce chronically impaired functioning (Wender,
1998). Developmentally, it seems that ADHD is heterogeneous clinically
(Biederman et al., 1992), genetically (Willcutt, Penninton & DeFries, 2000)
and neurophysiologically (Banaschewski et al.,2003a). Research has
shown that environmental adversity is significantly associated with ADHD
and its comorbid impairments (Biederman, 2002). The purpose of this
study is to describe childhood social adversities in a sample of Brazilian
adults with ADHD.
Method: Thirty-three DSM-IV ADHD patients of both sexes self referred
to a specialized center for ADHD were interviewed using DSM-IV. As an
index of childhood social adversity, we used an adapted version of the
Rutter scale (Rutter, 1988).
Results: The sample (19 men and 15 women) ranged in age from 18 to
47 years (mean: 32,6), with their level of education achievement ranging
from 12 to 18 years. A significantly percentage of subjects (73,5%) were
unmarried and (39,4%) unemployed. We found a great level of childhood
environmental adversities: 54% showed family conflicts, 45,8% low
socioeconomic status, 41,6% large sibship (34), 23,5% maternal psychopathology, 20,5% sexual abuse and 14,7% physical abuse.
Conclusion: Our results support a high prevalence of childhood environmental adversities in a sample of adults with Attention Deficit
Hyperactivity Disorder.
References: 1. Biederman, J. Further evidence for family-genetic risk factors inattention deficit hyperactivity disorder. Patterns of comorbidity in
probands and relatives psychiatrically and pediatricallyreferred samples.
Archives of General Psychiatry. 1992;49 (9):728-738. 2. Willcutt, E.G.,
Pennington, B.F., & DeFries, J.C. Twin study of the etiology of comorbidity
between
readingdisability
and
attention-deficit/hyperactivity
disorder.American Journal of Medical Genetics. 2000; 96 (3): 293-301.
3. Banaschewski, T., Brandeis, D., Heinrich, H., Albrecht, B.,Brunner, E.,
& Rothenberger, A. Association ofADHD and conduct disorder - brain
electrical evidence for the existence of a distinct subtype.Journal of Child
Psychologyand Psychiatry. 2003;44(3):356-376. 4. Joseph Biederman, J.,
Faraone, S.V., Monuteaux, M.C.Differential effect of environmental
adversity by gender: Rutters index of adversity in a group of boys and girls
with and without ADHD.Am J Psychiatry. 2002;159(9):1556-62. 5. Rutter
M: Studies of Psychosocial Risk: The Power of Longitudinal Data.
Cambridge, UK, Cambridge University Press, 1988
P-24-09
Relationship between the severity of Attention-Deficit
Hyperactivity Disorder (ADHD) and comorbidities
Mario Louz
Introduction: Attention-deficit hyperactivity disorder (ADHD) has historically been considered mainly a disorder of childhood. However, follow-up
studies have found that the disorder persists into adulthood in as many as
30% to 50% of these cases (Mannuzza at al, 1993). Adults with ADHD
show high incidence of lifetime diagnoses of anxiety disorders (43% to
52%), major Depression (16% to 31%), substance dependence (32% to
53%) and personality disorders (7% to 18%) ((Biederman et al.,1993;
Barkley et al., 1996a) The purpose of this study is to describe a sample of
Brazilian adults with ADHD and the relationship between psychiatric
comorbidities and severety of ADHD.
Method: Thirty-three DSM-IV ADHD patients of both sexes self referred
to a specialized center for ADHD were interviewed using DSM-IV criteria
to evaluate comorbid conditions and Clinical Global Impression (CGI) to
asses ADHD symptom severity.
Results: The sample (19 men and 15 women) ranged in age from 18 to
47 years (mean: 32,6 years). A significantly percentage of subjects
(73,5%) were unmarried and (39,4%) unemployed. Thirty-two patients
(96,7%) were diagnosed with comorbid conditions. The most frequent
were: generalized anxiety disorder (48,4%), major depression (42,4%),
alcohol abuse (21,2%) dysthymia (18,1%), and social phobia (18,1%). In
relation to the severity of ADHD symptoms, 36,4% of patients showed
CGI35; 57,6% of patients CGI= 4 and 9% of patients CGI=3. There was
a relationship between frequency of comorbid conditions and the severity
of ADHD: patients with CGI35 showed an average of 2,81 comorbid diagnoses; CGI=4 showed 1,94 comorbidities and CGI=3 showed an average
of 1,6 comorbidities.
Conclusion: Our clinical ADHD sample showed a high prevalence of psychiatric comorbid conditions related to the severity of ADHD symptoms.
References: 1. Mannuzza S, Klein RG, Bessler A, et al: Adult outcome of
hyperactive boys: Educational achievement, occupational rank, and psychiatric status. Arch Gen Psychiatry.1993;50:565-576. 2. Biederman, J.;
Faraone, S.; Spencer, T.; Wilens, T.; Norman, D.; Lapey, K.A.; Mick, E.;
Lehman, B.K.; Doyle, A. Patterns of psychiatric comorbidity, cognition,
and psychosocial functioning in adults with attention-deficit hyperactivity
disorder. American Journal of Psychiatry. 1993;150:1792-1798. 3.
Barkley, R.A.; Murphy, K.R.; Kwasnik, D. Psychological adjustment and
adaptive impairments in young adults with ADHD. Journal of Attention
Disorders. 1996;1:41-54.
P-24-10
Childhood obesity and Attention Deficit Hyperactivity
Disorder: A newly described comorbidity
Anat Agranat-Meged
Jerusalem, Israel
Chane Deitcher, Gil Goldzweig, Lilach Leibenson, Magda Stein, Esti
Galili-Wiesstub
Introduction: The prevalence of Attention Deficit/ Hyperactivity Disorder
(AD/HD) among children with obesity has not been studied. This study
reports on a comorbidity found between childhood obesity and ADHD
among a subset of obese hospitalised children and suggests that ADHD
may present a risk fsctor in the development of obesity.
123
Method: School-aged children hospitalized for obesity (body mass

index(BMI)>85%) in a tertiary referral center underwant extensive evaluations and were prospectively assesed for comorbid AD/HD. The prevalence of AD/HD in the obese study group was compared to the general
popolation prevalence using the Chi square test.
Results: During a four year period, a total of 32 obese school-aged children were hospitalized and 26 were included in the study. We found that
over half (57.7%) suffered from comorbid AD/HD. The prevalence of
AD/HD among morbid obese hospitalized children was significantly higher (57.7%) than in the general population (10%),( p<0.0001).
Conclusion: AD/HD shows a high comorbidity among obese hospitalized
children but has been previously overlooked. The characteristic difficulty
in regulation found in AD/HD may be a risk factor for the development of
abnormal eating behaviors leading to obesity. We suggest that obese children should be screened routinely for AD/HD.
P-24-11
Short-interval test-retest interrater reliability of the
Spanish version of the structured clinical interview for
depressive disorder in students adolescents
German Rueda Jaimes
Paul Anthony Camacho Lopez, Jorge Augusto Franco Lopez, Mauricio
Escobar Sanchez, Alvaro Andres Navarro Mancilla
Introduction: The Structured Clinical Interview for DSM (SCID) is a widely
used semi-structured instrument to measure all DSM-IV disorders that has
shown a relatively high reliability. Psychometric data concerning to structured clinical interviews are affected by age and characteristics of the
population. The present study was designed to investigate the test-retest
interrater reliability of a Spanish version of the structured clinical interview
for major depressive disorder in community samples of students adolescents.
Method: All participants were interviewed by psychiatrist with the section
for current major depressive disorder from Spanish SCID - I clinical version;
after three to ten days another psychiatry realized the same interview.
Both, adolescent and second interviewer were blind to first interview
results. The statistical significance of kappa was tested by calculation of
z-score. All statistical tests were done in STATA 8.0. Significant difference
was accepted when de probability of mistake was inferior to 5%
(p<0.05).
Results: We interviewed one hundred sixty-four adolescents aged from
13 to 17 year-old; mean age was 15.3 year (SD 0.96); 125 (76.2%) were
female; formal scholarity ranged from 8 to 11 years and socioeconomic
status were low in 46 (28.4%), middle in 115 (70.9%), and high in 1
(0.62%). The prevalence of current major depressive episode was 20.7%
according to the first rater and 18.2% according to the second rater
(p=0.806). The test-retest levels of agreement between first rater and
second rater for current major depressive episode was Kappa coefficient
0.612 (CI 95% 0.457-0.765).
Conclusion: The results of this study suggest that SCID is reliability not
only in adults, as it was demonstrated previously, but also in adolescents.
New studies are necessary to prove the reliability of the different modules
of the SCID in adolescents.
References: 1. Spitzer RL, Forman JBW, Nee J. DSM-III field trials. I. Inicial
interrater diagnostic reliability. Am J Psychiatry 1979: 136:815-17. 2. Skre
I, Onstad S, Torgersen S, Kringlen E, High interrater reliability for the
Structured Clinical Interview for DSM-III-R Axis I (SCID-I). Acta Psychiatr
Scand 1991: 84: 167-73. 3. Weertman A, Arntz A, Dreessen L, van Velzen
C, Vertommen S. Short-interval test-retest interrater reliability of the
Dutch version of the Structured Clinical Interview for DSM-IV personality
disorders (SCID-II). J Personal Disord. 2003; 17: 562-7.
P-24-12
Validate of Leyton Obsessional Inventory - child version in
child and adolescent from Colombia
German Rueda Jaimes
Luis Alfonso Diaz Martinez, Mauricio Escobar Sanchez, Jorge Augusto
Franco Lopez, Alvaro Andres Navarro Mancilla, Laura del Pilar Cadena
Afanador
124
Introduction: The Obsessive Compulsive Disorder (OCD) diagnosis is

complex and implies the realization of an interview for a trained professional. Nevertheless, several scales self-report exist for screening, which
the Leyton Obsessional Inventory - Child Version (LOI-CV) is the most used
in United States and Europe. In Colombia there are not scales validate for
TOC. The objective of this study is determine the internal consistency, factorial structure, reliability and criteria validity of the LOI-CV.
Method: Study of validation with probabilistic sampling. Participants:
581 students selected at random. Principal measures: The Inventory and
the Structured Clinical Interview for axis I of the DSM-IV (SCOD-I), clinical
version was applied; Cronbachs Alfa, factorial analysis, sensibility, especificity, likelihood, and Lins coefficient were calculated.
Results: Compulsive obsessive disorder prevalence was 11,8% (95%CI
8,9-14,6). Cronbachs alpha was 0,803 and there was only one factor
with 3,60 eigenvalue; this factor explains 74,8% of the variance. The area
under ROC curve was 0,799 (95%CI 0,752-0,847) and the best cut-off
point was 12, with sensitivity in 69,5% (IC95% 56,0-80,5) and specificity
in 77,7% (IC95% 72,9-88,9). Its reliability was acceptable (Lins coefficient in 0.752; 95%CI 0,714-0,790).
Conclusion: The Leyton obsessional inventory - child version is a fairly
screening tool in Colombian children and adolescents.
References: 1. King N, Inglis S, Jenkins M, Myerson N, Ollendick T. Testretest reliability of the survey form of the Leyton Obsessional InventoryChild Version. Percept Mot Skills 1995;80:1200-2. 2. Berg CJ, Rapoport
JL, Flament M. The Leyton Obsessional InventoryChild Version.
Psychopharmacol Bull. 1985;21:1057-9. 3.Berg CZ, Whitaker A, Davies
M, Flament MF, Rapoport JL. The survery form of the Leyton
Obsessionality Inventory-Child Version: norms from an epidemiological
study. J Am Acad Child Adolesc Psychiatry 1988; 27: 759-63. 4. Bamber
D, Tamplin A, Park RJ, Kyte ZA, Goodyer IM. Development of a short
Leyton obsessional inventory for children and adolescents. J Am Acad
Child Adolesc Psychiatry. 2002; 41:1246-52.
P-24-13
Prevalence of obsessive-compulsive disorder on Colombian
adolescents and its association with working while going
to school
Alvaro Andres Navarro Mancilla
German Eduardo Rueda Jaimes, Paul Camacho Lopez, Jorge Augusto
Franco Lopez, Mauricio Escobar Sanchez, Luis Alfonso Diaz Martinez
Introduction: In the US and Europe the prevalence of obsessive compulsive disorder (OCD) ranging from 0.1% to 4% in people younger than
18 years. (1-3) However, there are no data on the prevalence of OCD in
this population in Latin America. The purpose of this study was to estimate the prevalence of OCD in children and adolescents attending school
in Bucaramanga-Colombia, and to determine its associated socio-demographic factors.
Method: A cross-sectional design was used with a sample size of 501
individuals aged 10 to 17 years enrolled in Bucaramangas schools by
2005. They were administered a structured clinical interview (SCID-I clinical version, OCD module). Socio-demographic data was also collected.
The inquired sociodemographic factors were analyzed with non conditional logistic regression.
Results: Prevalence of OCD was found to be 7.4% (95% CI 5.3 - 10.0)
in this population. Students with OCD had a prevalence of working for
money higher than those who did not (PR 2,23; 95% CI: 1.01 - 4.39).
Girls who worked for money showed a higher risk of having OCD than
those who did not (OR 5,43 CI 95% 1,7 - 3,84), in a logistic regression
model.
Conclusion: These results suggest that the prevalence of OCD among
Colombian school children is higher than elsewhere. In addition, working
while going to school might be a risk factor associated with OCD in girls.
References: 1. Manzini F, Gragnani A, Orazi F, Pietrangeli MG.
Obsessions and compulsions: normative data on the Padua Inventory
from an Italian non-clinical adolescent sample. Behav Res Ther 1999; 37:
919-25. 2. Flament MF, Whitaker A, Rapoport JL, Davies M, Berg CZ,
Kalikow K, et al. Obsessive compulsive disorder in adolescence: an epidemiological study. J Am Acad Child Adolesc Psychiatry 1988; 27: 764771. 3. Douglass HM, Moffitt TE, Dar R, McGee R, Silva P. Obsessive-compulsive disorder in a birth cohort of 18-year-olds: prevalence and predictors. J Am Acad Child Adolesc Psychiatry 1995; 34: 1424-31.
P-24-14
Main psychopathologies diagnosed at the institution of
infantile neuropsychiatry professor heitor carrilho
Francisco Ribeiro Jr
Universidade Federal do Rio Grande do Norte, Natal, Brazil
Introduction: This work analyzes the prevalence of the psychopathologies
diagnosed in the patients medical dossier at the institution Professor
Heitor Carrilho, a clinic of infantile neuropsychiatry which stays in NatalRN - Brazil.
Method: Retrospective work, analyzing 176 patients medical dossier,
embracing all the age groups, of the last five years (2001 to 2005). The
research based on the age, the sex and the diagnosis of each patient, trying to know, mainly, the psychopathologies diagnosed (according to
International Classification of Disease - ICD) in the initial evaluation.
Results: Of the 176 patients, 107 (60.80%) belonged to the masculine
sex. In the date of the first consultation (when the patient gave entrance
in the institution), 59.09% of the patients were children and 24.43%,
adolescents. In relation to the psychopathologies, the most found were:
F70-F79 Mental Retard (22.16%); F90-F98 Behavior and Emotional
Disorder that habitually appear during the childhood or the adolescence
(14.20%), of the which the hyperkinetic (F90) is the most prevalent; F80F89 Psychological Development Disorder (10.23%), with larger evidence
for the specific of the development of the speech and of the language
(F80); Syndrome of Down (6.81%); Autism (2.84%); 10.80% presented
other neurological and psychic diseases like Bipolar Disorder, Depression
and Degenerative Syndromes; 13.07% possessed other diseases, mainly
of the endocrine metabolism, as Diabetes mellitus and Hypothyroidism.
11.36% presented more than one disease. In 19.89% of the patients
assisted initially, there was not registration of the diagnosis in the medical
dossier.
Conclusion: The child represents the patients largest portion that arrives
at the institution for a first attendance, being the Mental Retard the diagnosis most initial prevalent in all the age groups, so much in the cases of
only one psychopathology as in the cases with more than one disease. It
is still important to evidence the high number of patients without certain
diagnosis in the medical dossier.
P-24-15
Psychic and biological alterations in a child with syndrome
of Williams
Universidade Federal, do Rio Grande do Norte, Natal, Brazil
Introduction: The objective of this work is to evidence the biological and
psychic alterations involved in a child, that was assisted in service of infantile neuropsychiatry, and whose diagnosis was Syndrome of Mohr.
Method: Approach to the patient, obtaining information of the disease
in relation to the beginning and course, until the current days, his physiologic and pathological antecedents and his family pathological history,
followed by psychiatric interview, neurological evaluation, general physical exam and investigation of specific exams.
Results: Patient with Syndrome of Mohr, since his birth, presented organic
alterations, as neonatal hypoglycemia, inguinal hernia, heart bruit and
gastro-esophageal reflux. He presented delay in the neuropsychological
development, coming to stroll only to the 02 years and 06 months, after
physiotherapy. Nowadays, he possesses difficulty to interact with other
children, being always very concentrated, mainly, when he is listening to
music. He has great musical ability and studies in conventional school, but
he doesnt tend nor good adaptation neither good development. In the
physical exam, it was noticed small and sheer nose, coiled hair, full lips
and small teeth. During the psychic exam, he was hyperactive, agitated,
restless and with little interaction. In the other exams, the ecocardiography evidenced discreet stenosis in left lung branch and descending aorta.
Accomplished PCR, the patient presented deletion of the elastin gene in
the chromosome 7.
Conclusion: Great sensibility to the sounds, psychic isolation, anxiety and
hyperactive are the psychic alterations evidenced and elastin gene deleted in the chromosome 7 is the most important biological alteration.
P-24-16
Psychiatric comorbidity and behaviour in children and adolescents with migraine
C Wanner
A. Zormann, G. Wagner, C. Wber, H.E. Zesch, C. Kienbacher, A.
Konrad, G. Berger, A. Karwautz, C. Wber-Bingl
Introduction: Association of headache with depression and anxiety in
adults are well examined and defined. Children, who are brought to medical attention because of frequent and recurrent or disabling headaches
often appear to have a high prevalence of psychiatric comorbidity. We
hypothesized that migraine with and without aura are differently associated with internalizing and externalizing symptoms in children and adolescents. Methods: We aimed to investigate internalizing and externalizing symptoms (Child Behavior Checklist, CBCL - Achenbach 1991) in a
retrospective study of referred patients from the same Headache
Outpatient Department at Vienna University with migraine with and without aura using the IHS-criteria. We examined 305 children and adolescents, among those were 164 with migraine without aura (MO), 56 with
migraine with aura (MA) and 55 controls without headache (no HA). The
parents completed the Child Behavior Checklist (CBCL - Achenbach
1991). We used SPSS 13 applying Kruskal-Wallis Test, Mann-Whitney UTest and Bonferroni-Holm Correction. Results: Internalizing symptoms
showed significantly higher levels in migraine with and without aura compared to controls. Social problems were highest in migraine with aura
(MA). Overall little difference between both migraine groups (MA+MO).
Conclusions: Systematic assessment of psychiatric comorbidity in children
and adolescents with migraine is important to provide useful medication
for young patients in order to avoid chronification and aggravation of
internalizing symptoms.
125
NEUROGENERATIVE DISORDERS - Poster
P-12
Neurodegenerative Disorders
P-12-01
Subthalamic deep brain stimulation in Parkinsons disease
and mood disorders, one-year follow-up
Isabelle Chereau-Boudet
CHU Clermont-Ferrand, Psychiatry B, France
Ingrid de Chazeron, Philippe Derost, Miguel Ulla, Jean-Jacques Lemaire,
Franck Durif, Pierre-Michel Llorca
Introduction: Several cases of transient acute depression or manic symptoms are reported in the literature after bilateral subthalamic nucleus
(STN) deep brain stimulation in patients with Parkinsons disease.
Different hypothesis involve premorbid personality disorders, thymic past
history or subthalamic nucleus.
Method: We elaborate a one year prospective study to evaluate mood
disorders frequency and physiological mechanisms of 20 Parkinsonian
patients treated by bilateral STN stimulation. Evaluation consists of pre
and post-operative psychiatric interview and scales assessing depression
and mania.
Results: 18 patients have been selected, and operated. 17 patients have
finished the program. Meaning age of patients: 63,1 years 7,3, with
5 women. No significant differences between men and women age, and
duration of Parkinson disease (11,9 4,4), were found (n=18). One month
before surgery, MADRS, Bech and Beck means (n=18) are respectively: 7,2
4,2; 1,3 1,6; 6,4 3,5. At 3 months after surgery means (n=18) are:
3,9 3,8; 1,1 1,6; 3,1 2,6. At 6months after surgery means (n=17) are:
6,7 4,8 ;0,65 1,1 ; 3,80 2,6. One patient, 70 years old, has presented a hypomanic-like episode (DSM IV criteria) post-operatively following
adjustment of the stimulation settings. One patient, 68 years old, with a
20 year history of Parkinsons disease, presented a major anxio-depressive
episode month post-operatively (DSM-IV criteria). One patient, 53 years old,
with 13-year history of Parkinsons disease, presented a moderated anxiodepressive episode, 6 months after surgery.
Conclusion: Data are still on analysed, but these cases draw our attention to the effects of STN stimulation on mood and behavioural disorders.
The difference since auto and hetero evaluation in depressive symptoms
may be related with problem of insight. Lastely importance of psychiatric
follow-up is revelated by these results.
References: 1. Krack P, Batir A, Van Blercom, N, Chabardes S, Fraix V,
Ardouin C, Koudsie A, Dowsey Limousin P, Benazzouz A, Lebas JF,
Benabid, AL, Pollak P. Five-Year Follow-up of Bilateral Stimulation of
Subthalamic Nucleus in Advanced Parkinsons Disease. N Engl J Med
2003, Nov; 13, 349;20: 1925-34. 2. Houeto JL, Mesnage V, Welter ML,
Mallet L, Agid Y, Bejjani BP. Subthalamic DBS replaces levodopa in
Parkinsons disease: two-year follow-up. Neurology. 2003, Jan 14; 60 (1):
154-5.
Conclusion: The role played by modulation of STN activity, the idea of a

potential stimulation intensity threshold, the previous history of mood
disorders, and the impact of antiparkinsonian treatment could be related
to post-operative manifestations of mood disorders. As things stand, further investigation of the pathophysiological mechanisms underlying mood
disturbance and a closer follow-up of this surgical technique are needed
in order to better control the side effects of this treatment.
P-12-03
Dementia diagnosis disclosure: Patient and caregiver
experiences
Anna Byszewski
The Ottawa Hospital, Geriatrics, Canada
F. Molnar, F. Aminzadeh
Introduction: With improved diagnostic accuracy and emerging treatment strategies for Alzheimer's disease, disclosure becomes more important, and health care professionals need information regarding the optimal manner in which to provide these diagnoses and to manage all
aspects of dementia care, including driving cessation.
Methods: A qualitative study was conducted with 30 patients diagnosed
with dementia and and their caregivers who had participated in a meeting where the diagnosis was disclosed. Data was collected from disclosure meetings, patients and caregiver interviews and three caregiver focus
groups.
Results: 20 women and ten men diagnosed with dementia (and their
caregivers) were recruited. The age range was 71-92 and MMSE ranged
from 15-29. Of the sample, 11 had Alzheimer disease, 7 had vascular
dementia and 12 a mixed dementia. Patients' emotional responses included, shock, disbelief and anger. Patients spoke of the loss and stigma
associated with the diagnosis. The most challenging topic was discussion
around safety driving.Caregivers provided insight about the patient
response in the short term and provided advice on the disclosure process.
Recommendations included emphasizing hope in the face of a difficult
diagnosis, encouraging the use of progressive disclosure to allow the
person and caregivers to prepare, and providing more detail about the
condition. Results of this study have been used to plan/develop:1.
Frequently asked questions (FAQ) - this is a summary of questions and
answers commonly asked in the meetings and to be provided with the
written team discharge summary. 2. Team collaboration scale - this will be
a tool that will be validated and used to encourage formative assessment
and a teaching tool for new trainees.3. In-service - this will be a program
developed to incorporate recommendations from the study for new team
members 4. Recommendations for physicians - based on patient/caregiver a list of key points to consider when disclosing diagnosis and for discussing driving cessation.
Conclusion: This study provides actual perspectives from patients with
dementia and their caregivers. Information gained from the study will
assist with the disclosure process, including counseling and appropriate
follow up care to patients newly diagnosed with dementia.
P-12-02
Manic and hypomanic episodes following deep-brain stimulation of the subthalamic nucleus in parkinson's disease
P-12-04
Bipolar disorder in old age: Treatment and clinical course
I. de Chazeron
CH4 Clermont-Ferrant, Psychiatry B, France
Ingrid de Chazeron, P. Derost, J. J. Lemaire, F. Durif, P. M. Llorca
Paula Nunes
Institute of Psychiatry, Department of Psychiatry, Sao Paulo, Brazil
Priscilla Paganelli, Orestes Forlenza
Introduction: In the last few years, deep brain stimulation of the subthalamic nucleus (STN) has given very promising motor performance results
as a treatment tool in advanced forms of Parkinsons disease, however
post-operative major psychiatric complications may be wait.
Methods: We examined the onset and evolution of manic or hypomanic
manifestation in three cases of parkinsonian patients having deep brain
stimulation of the STN.
Results: These patients present its manifestations relatively quickly following the surgery. For all, many questions remain concerning the role played by the modulation of the subthalamic nucleus activity in the onset of
these disorders, the role of previous history of mood disorders, and the
impact of the antiparkinsonian medication. We note the occasionally atypical nature of the manifestations.
Introduction: There are few works in literature of bipolar disorder in old

age. This population is at risk for dementia and might have special needs
and tolerability for its treatment. Through a systematic monthly review of
the mood status and treatments in a mood chart it is possible to verify
best doses and responses.
Method: In 57 patients with bipolar disorder and 60 years of age or more
a retrospective chart review was made. All medications used and its
doses, mood status and other clinical outcomes were observed.
Results: Patients had on average 68,3 (SD 5,3) years and were followed
through 88 (56) months (approximately 7 years). Euthymia was present
in 69% ( 27) of the time, euphoria 10% (13), depression 20% (25)
and mixed state 1% (4). Good response to euphoria was observed with
lithium in 42 subjects (on daily doses of 809mg on average). For valproate
126
22 subjects had similar response (on daily doses of 1297mg on average)

and for carbamazepine 11 subjects (on daily doses of 644mg on average).
A second mood was used in 45% of time. Good response to depression
was found for lithium in 32 subjects, for valproate in 11 subjects and for
carbamazepina in 4 subjects. An antidepressant was associated in 73% of
time.
Conclusion: A great heterogeneity was observed in the clinical course of
the bipolar disorder in old age. Depression was more prevalent than
euphoria or mixed state. Lithium was the medication used with greater
frequency. Globally, best therapeutic results were obtained with lithium
and valproate alone or associated with a second mood stabilizer (for
mania) or a antidepressant (for depression).
References: none
P-12-05
Peripheral biochemical markers in early and late onset
Alzheimers disease
Ninoslav Mimica
Psychiatric Hospital Vrapee, Psychiatry, Zagreb, Croatia
Dorotea Muck-Seler, Nela Pivac, Maja Mustapic, Paula Presecki, Vera
Folnegovic-Smalc
Introduction: Alzheimers disease (AD) is a multifactorial and complex
disorder. The age of the onset and the course of AD could be related to
the lifestyle, genetic, socidemographic, environmental, clinical and pharmacological factors. Post mortem brain studies indicated that the alterations in neurotransmitters systems could be involved in the ethiology
and progress of AD. The aim of the study was to determine peripheral
biochemical markers (platelet serotonin/5-HT/ concentration, and the
activity of platelet monoamine oxidase type B /MAO/ and plasma
dopamine-beta hydroxylase /DBH/) in patients with AD subdivided according to the onset of disease and to the presence of psychotic features.
Method: The study included 43 male and 144 female patients with AD
subdivided in two groups according to early (before the age of 64 years)
or late (after the age of 65 years) onset of AD. The diagnosis of the probable AD fulfilling NINCDS-ADRDA criteria was established according to
the ICD-10 and DSM-IV-TR criteria. Mini Mental Status Examination
(MMSE) was used to assess the cognitive impairment. The control group
consisted of sex and age-matched medication free healthy subjects
(65 female and 51 male). Platelet 5-HT concentration and platelet MAO
activity were determined using spectrofluorimetric methods, and plasma
DBH using photometric method.
Results: Platelet 5HT concentration, and plasma DBH activity were
decreased, while platelet MAO activity was increase in patients with AD.
The highest platelet MAO activity was found in male and female patients
with early onset AD. Patients with late onset AD had lower values of plasma
DBH activity as compared with patients with early onset AD and healthy
controls. The changes in biochemical parameters were not related to the
presence of psychotic features.
Conclusion: The results of this ongoing study, support the presumption
that platelet 5-HT concentration, platelet MAO and plasma DBH activity
could be used as the peripheral biological markers for different categories
of AD. In addition high platelet MAO B and low plasma DBH activity could
be the predictors of the AD. Our results of the altered MAO and DBH
activity in patients with AD, support the presumption that toxic and reactive metabolites of catecholamine neurotransmitters could be involved in
the ethiology of AD.
P-12-06
Cerebral glucose metabolism in patients with Alzheimers
disease
Pablo Toro
Germany
Peter Schoenknecht, Aoife Hunt, Marcus Henze, Uwe Haberkorn,
Johannes Schroeder
Introduction: Alzheimers disease (AD) is characterized by severe cognitive deficits involving different cognitive domains such as memory decline,
language deficits, and apraxia. Although, memory impairment has been
addressed in recent neuroimaging studies the neural substrates of most

cognitive deficits in AD, which can be reliable be assessed by using the
neuropsychological test battery of the Consortium to Establish a Register
for Alzheimers Disease (CERAD), remain unresolved. To this concern,
positron emission tomography (PET) has been proofed an adequate
method for unrevealing the neural substrates of cognitive dysfunctions.
Method: 45 patients with AD were investigated with 18F-2-fluoro-2deoxy-D-glucose (FDG) PET. In all patients, the neuropsychological test
battery of the CERAD was applied. Using statistical parametric mapping
significant correlations were calculated to assess the association of cerebral glucose metabolism and neuropsychological test performance
Results: Significant correlations between memory test scores and activation of temporo-frontal and cingulate cortices occurred. Verbal fluency
and naming scores were significantly correlated with predominantly left
temporo-parietal and frontal cortices. Irrespective of domain, delayed
memory performance was associated with a network including frontal
association cortices.
Conclusion: The findings demonstrate that in AD, neuropsychological
deficits as assessed by the CERAD involve different cerebral sites and thus
underline the clinical validity of this clinical instrument.
P-12-07
Cerebrospinal fluid tau protein levels in the early
diagnosis of AD
Pablo Toro
Germany
Peter Schoenknecht, Elmar Kaiser, Philipp Thomann, Johannes Schroeder
Introduction: In Alzheimers disease (AD), an accelerated neurofibrillary
tangle formation occurs which is associated with the release of microtubuli associated tau protein into the cerebrospinal fluid (CSF). Recent
studies found significantly increased CSF tau levels in patients with AD in
comparison to controls indicating the potential relevance of this protein
as a molecular marker of AD. Since early diagnosis of AD has the potential to improve therapeutic interventions both total tau and phosphorylated tau (phospho-tau) have to be investigated in patients with mild cognitive impairment (MCI) and AD.
Method: 132 patients with AD, 29 patients with MCI diagnosed according to the criteria of aging-associated cognitive decline (AACD), and
24 controls were included. In all participants, CSF total tau and tau protein phosphorylated at threonine 181 concentrations were determined by
ELISA. Total tau and phospho-tau levels were compared between mild
AD, moderate AD, severe AD, MCI, and controls.
Results: CSF total tau levels are elevated in patients with severe and
moderate AD, differing significantly from patients with mild AD, patients
with MCI, and controls. In mild AD and MCI, total tau levels are between
severe and moderate AD, and controls, respectively, differing significantly
from both. CSF phospho-tau levels are significantly elevated in severe AD
compared to moderate and mild AD, MCI, and controls.
Conclusion: The results underline the importance of CSF total and phospho-tau protein concentrations in the diagnosis of early AD. From a clinical point of view, one may conclude that increased tau levels confirm the
clinical diagnosis of AD, however, normal values do not exclude the disease.
P-12-08
MR-morphometric changes and their association with neuropsychological performance in patients with mild cognitive impairment
Vasco dos Santos
Psychiatrische Universittsklinik, Sektion fr Gerontopsychiatrie,
Heidelberg, Germany
Pablo Toro, Philipp Thomann, Ulrich Seidl, Frederik Giesel, Marco Essig,
Johannes Schroeder
Introduction: The objective of this study is to reveal the associations of
structural cerebral alterations with neuropsychological deficits in patients
with mild cognitive impairment (MCI).
127
Method: 53 patients with MCI, 26 patients with mild AD and 30 healthy

controls underwent structural magnetic resonance imaging (1,5 Tesla).
We use optimized voxel-based morphometry (VBM) to investigate (a) differences in gray matter (GM) density between the three groups and (b)
the putative relation of neuropsychological performance (CERAD) to specific structural alterations.
Results: In relation to healthy comparison subjects, loss of GM density in
MCI subjects was accentuated in the temporal lobe (both neocortical
fields and substructures of the medial temporal lobe) and in parietal
regions. Congruent results were revealed when control subjects were
compared to patients with AD, indicating that MCI indeed represents its
preclinical stage.
Conclusion: We are currently analyzing the associations between GM
density and several scores in neuropsychological performance; results will
be presented at the congress.
P-12-09
Depression and visual hallucinations in patients with
Parkinsons disease
Zoja Babinkostova
University Clinical Centar, Clinic of Psychiatry, Skopje, Macedonia,
Republic of the former Yugoslavia
D. Petreski
Introduction: Depression has been shown to be more common in
Parkinsons disease (PD) than in other chronic and disabling disorders. The
most common manifestation of psychosis in Parkinsons disease is visual
hallucinations.
Method: 32 patients with idiopathic PD underwent psychiatric, neurological and brain imaging (CT or MRI) evaluation. Psychiatric diagnosis
was performed by semistructured interview according with ICD-X criteria
and the severity of symptoms was rated with clinical rating scales
(Hamilton Rating Scale for Depression; Baylor PD Hallucination
Questionnaire). Also all patients were evaluated using the Unified
Parkinsons Disease Rating Scale.
Results: Depressive symptoms were present in more than half of the
patients - 59,4% (n=19). 25% of the patients (n=8) had visual and figurative hallucinations. Depression appears to be associated with increased
disability and reduced quality of life. Visual hallucinations were significantly associated with higher depression score and worse disease severity.
Hallucinations were not associated with history of psychiatric disease.
Conclusion: Previous studies suggest a neurobiological basis for most
psychiatric symptoms, although psychological factors are probably involved
in the development of affective disorders. Visual hallucinations most
probably result from the combined effect on dopaminergic and serotonergic systems in the CNS.
P-12-10
Evaluation of interests centers
Daniel Dachesky
School of Medicine Rosario, Dept. of Psychiatric, Argentina
Philippe Robert
Introduction: The evaluation of this domain is extremely important in
Alzheimer Disease considering the fact that the persistence of the interest
is recognized as a potential protective factor against the development of
a dementia. The interest test has been developed to allow the evaluation
of centers of interest and of activities carried out in old people, with or
without degenerative pathology. This study is to present the first results
linked to the use of this test.
Method: The test is composed of pictures that illustrate daily activities or
of leisure. The normative data have been carried out on the selected 50
pictures. In a second stage, 38 subjets (average age =76,6 ; DS=7,3) that
presented an Alzheimer Disease (AD) ; 10 subjets (average age =77,5;
DS=8) that presented minimum cognitive impairment (MCI), and their
caregivers. The number of centers of interest has been evaluated by each
patient and its caregiver. The data have been compared with a population
of 39 control subject (average age=76,2 ; DS +4,4). Also, the Apathy
Inventory has also been used in these subjets that presented of AD or a
MCI.
128
Results: From caregivers evaluation, the number of interest is significantly smaller for AD subjects and MCI comparatively with controls (F = 9,01;
p <0,0001). on the contrary, they are not differences concerning the
number of the interest between subject AD and MCI. A significant correlation exists (test of Piearson: r = 0,65 ; p <0,001) among the evaluation
of the score of interest among the caregivers values and for the patient.
On the contrary, a significant correlation doesnt exist (r = 0,255) among
the evaluation of the loss of interest for the control and the caregiver with
the Inventory Apathy
Conclusion: The test of interest allows to evaluate in a more precise way
that would make it a simple questionnaire the interests of the subjets that
suffer AD. These characteristics transform it in a tool adapted to the non
pharmacological evaluation of clinical elements of intervention in neurodegeneratives pathologies in old people. Indeed, the test of interest
proposes a wide inventory of activities that can be developed by old people and whose administration allows a more objective evaluation of the
apathy for the subjet.
P-12-11
Results from a comparison of apraxia in Huntingtons
disease vs. Alzheimers disease
Anna Hoedl
Department of Psychiatry, Graz, Austria
Daniela V. Otti, Rottraut Ille, Raphael M. Bonelli
Introduction: Introduction: Ideomotor limb apraxia is a common sign in
patients with Alzheimers disease (AD) and a diagnostic criterion for AD in
ICD-10 and DSM-IV TR. In patients with Huntingtons disease (HD), a rare,
devastating neurodegenerative disorder, the occurrence of apraxia is still
controversial. Recent studies described an occurrence of apraxia in HD
(Shelton and Knopman 1991; Hamilton et al. 2003), but until now there
has not been a detailed comparison between apraxia in AD and HD.
Method: Methods and Patients: To assess the occurrence of apraxia in
patients with AD and HD, 23 in-patients with AD and 24 in-patients with
HD, treated at the Department of Psychiatry at the Graz Medical
University, were examined in i) imitation of hands movements, ii) imitation
of fingers movements, iii) execution of gestures on demand, and iv) execution of pantomimic movements. AD- and HD-patients did not differ in
gender distribution and in severity of dementia (assessed by Mini Mental
State Examination), but due to the earlier beginning of the illness HDpatients were significantly younger (44.2 a) than AD-patients (74.0 a).
Results: Results: In AD-patients apraxia occurred from 12.9% in the
assessment of hands imitation up to 29.0% in the assessment of fingers
imitation and gestures; in HD-patients the occurrence of apraxia was
found from 36.8% (gestures) to 73.7% (pantomime). In the comparison
of AD- and HD-patients assessment of fingers imitation and gestures no
difference was found, in the assessment of hands imitation and pantomime HD-patients scored significantly lower than AD-patients.
Conclusion: Conclusion: Until now apraxia was said to be an exclusive
sign of cortical dysfunction but obviously apraxia also may occur in subcortical dementia. There are distinct differences in occurrence of apraxia
in AD and HD, for until now we do not know yet the underlying pathological pathway causing apraxia in each disease.
P-12-12
Primacy and recency effect in Huntingtons disease
Brigitte Juliane Herranhof
Medical University of Graz, Psychiatry, Austria
Karin Reisinger, Daniela Otti, Anna Hdl, Raphael Maria Bonelli
Introduction: Huntington disease (HD) is a neurodegenerative disorder
due to an excessive number of CAG repeats in the IT15 gene on chromosome 4. Studies showed indifferent results in selected memory functions.
This study, which is still going on till January 2007, will concentrate on the
primacy and the rececency effect in HD.
Method: As a part from a larger study till yet 56 patients (34 men and
22 women) in the age between 24 and 67 with genetically proved HD
were included. A five-point disease stage was assigned, based on the
total functional capacity score (Shoulson, 1981). The UHDRS was also
included. All patients have to complete the Multiple Choice Vocabulary
Test, Version B (Lehrl, 1977), the Mini-Mental-State-Examination (Folstein,

1975) and a German Version of the California Verbal Learning test
(Ilmberger, 1988). It is planned to recruit about 40 controll participants
without a HD diagnosis most of them colleagues and healthy family
members. Controlls and patients should be matched as closely as possible for age, sex, years of education and handedness.
Results: The first question to answer is, whether the primary or secondary
brain effort of HD patients is more affected compared to controlls. To
answer this question measures of the primary and secondary brain from
Salthouse (1980) will be used. Only the first learning trial of the CVLT is
for this question important. In a further step we will looking for the difference between primacy and recency effects above all five learning trials
in CVLT, we expect a difference between the groups (HD, controlls).
Furthermore we hypothesise generally the recency effect in HD Patients is
higher than the primacy effect.
References: Shoulson, I. (1981). Huntingtons disease: Functional capacities in patients treated with neuroleptic and antidepressant drugs.
Neurology, 31, 1333-1335 Lehrl S (1977) Mehrfach-WortschatzIntelligenztest MWT-B. Straube, Erlangen Folstein, M., Folstein, S., &
McHugh, P. R. (1975). Mini-Mental State: a practical method for grading
the cognitive state of patients for the clinician. Journal of Psychiatric
Research, 12, 189-198 Ilmberger, J. (1988). Deutsche Version des
California Verbal Learning Test. Institut ffir Medizinische Psychologie der
Universitt Mfinchen Salthouse, T. A. (1980). Age and memory: strategies for localizing the loss. In Poon L. W., Fozard J. L., Cermak L. S.,
Arenberg D. E., Thompson L. W. (Eds.), New directions in memory and
aging: Proceedings of the George A. Talland memorial conference (pp.
47-65). Hillsdale, NJ: Erlbaum
P-12-13
Executive functions in Huntingtons disease
Nicole Mller
Graz, Austria
Anna Hdl, Brigitte Herranhof, Raphael Maria Bonelli
Introduction: Huntingtons disease (HD) is a hereditary and progressive
disease of the central nervous system and neuropsychological deficits are
a main feature of HD. Planning is defined as the ability to organize cognitive behaviour in time and space.
Method: 45 patients with gentically confirmed HD were tested with two
different test batteries (Tower of London TL-D, Behavioural Assessment of
Dysexecutive Syndrome BADS). The German version of the well known
test Tower of London (ToL TL-D) measures planning abilities and the speed
and accuracy of thinking. For this test, the patient is instructed to move
three different coloured balls to match a target configuration by using a
minimum number of moves. The Behavioural Assessment of the
Dysexecutive Syndrome (BADS) is a comprehensive neuropsychological
assessment battery designed for ecological validity and other measures
of frontal executive functions. The BADS is a test battery of six different
elements tests to investigate deficits in planning ability and the everday
difficulties. We compare these two tests to a large battery of other neuropsychological tests assessing memory, attention, visuoconstructive abilities, apraxia, to MRI findings of the 45 patients, to their psychiatric symptoms and motor function.
Results: The results are going to be presented at the congress.
P-12-14
Osteoporosis in Huntingtons disease
Daniela Verena Otti
University Clinic, Psychiatry, Graz, Austria
Anna Hoedl, C. M. Bonelli, A. Strele, B. Obermeyer-Pietsch,
H. P. Kapfhammer, R. M. Bonelli
cells and so non-brainrelated changes outside the CNS should be possible. The aim of the present study was to investigate correlation between
bone mineral density (BMD), body weight and antipsychotic burden in
HD. Decreased body weight is common among patients with HD and
decreased weight is strongly associated with decreased BMD.
Antipsychotic medication decrease BMD by increasing prolactin.
Method: 40 patients (18 male, 22 female) with HD were investigated in
this study. Blood samples were drawn (total serum calcium, phosphate,
alkaline phosphatase, thyroid hormones, free thyroxine, prolactine,
24(OH)vit-D3, CTX- crosslaps) and BMD was measured at the lumbar
spine and the hip by dual-energy X-ray absorptiometry.
Results: CAG repeats had a significant influence on age-adjusted total
hip BMD and on body weight. Age-adjusted BMD in HD patients was significant lower at the hip compared to controls (p = 0.031). When comparing CAG repeats with antropomorphic data we obtained significant
relations with total hip BMD (p=0.001), lumbar spine BMD (p=0.001) and
weight (p=0.019). 25(OH)vit-D3 levels were significantly lower (p=0.007)
and serum cross laps were significantly higher in HD patients (p= 0.015).).
The influence of antipsychotics on BMD is neglectable.
Conclusion: We found that body weight and BMD is CAG dependent in
HD patients. BMD in HD patients is lower compared to weight-adjusted
controls. It now appears that the Huntingtin mutation produces similar
disturbances in other parts of the body, yet the affected cells somehow
cope.
P-12-15
Urodynamic in Huntingtons disease
Daniela Verena Otti
University Clinic, Psychiatry, Graz, Austria
Michael Koppitz, Sabine Obmann, Markus Magnet, Anna K. Hdl,
Gnther Primus, Hans-Peter Kapfhammer, Raphael M. Bonelli
Introduction: Dysfunction in urinary bladder is common in patients with
Huntingtons disease (HD), which is an autosomal dominantly inherited
neurodegenerative disorder due to an increase of CAG repeats in chromosome 4p13. HD is characterised by neurodegenerative symptoms
(movement disorder like chorea or gait disability), psychiatric manifestations and progressive dementia. In literature we found only one study
concerning the urodynamic disturbances in HD (Wheeler JS et al.). We
tried to investigate if there is a characteristic urodynamic pattern affecting
the vesico-urethral function in HD patients, in correlation to genetic
imprinting (CAG-Repeats) and the state of disease.
Method: 31 HD patients (18 male, 13 female) underwent urological
measurements (nativflow, urinary-bladder detrusorpressure, maximum
capacity of bladder, changes in pressure during filling and depleting,
occurence of detrusorcontraction, loss of urine) and general evaluations
of urological complaints and were compared to 31 sex- and age-matched
healthy controls.
Results: HD patients had significant variances (p=0.014) in urodynamic
parameters concerning the dysfunction of the urinary bladder (in particular
in detrusorcontraction and -pressure) in all stages of disease. HD patients
had a significantly increased detrusorpressure (44%) as compared to controls (p=0.014). 29% of HD patients featuring bladder-contractions (7%
of healthy controls). The frequency of nocturnal miction (nocturia) in HD
patients is 105,5% comparing to controls.
Conclusion: HD patients had significant noticeable problems in urodynamic compared to controls. We found no correlation between the urodynamic parameters and the quantity of CAG-repeats or the stage of disease. None the less our findings indicate the question to which extent disturbances in the function of urinary bladder influence the quality of life.
Introduction: Huntingtons disease (HD) is an autosomal dominantly

inherited disorder characterized by neurodegenerative symptoms (psychiatric manifestations, movement disorders, progressive dementia). An
unstable expansion of Cytosin-Adenin-Guanin CAG) trinucleotid repeat
on the short arm of chromosome 4 leads to expanded polyglutamine reapeats in the protein Huntingtin. These cellular changes result in neuronal
degeneration in the brain but the CAG repeat expansion is present in all
129
P-25
Neurodegenerative Disorders II
P-25-01
Neuropsychological frontal lobe dysfunctions in mild
cognitive impairment and elderly depression
Alina Borkowska
Nicolaus Copernicus University, Collegium Medicum Neuropsychol,
Bydgoszcz, Poland
Wiktor Dro, Marzena Ziolkowska-Kochan, Janusz Rybakowski
Introduction: Mild Cognitive Impairment (MCI) has been defined as a
heterogenous group of cognitive dysfunctions which may represent a
transitional state between normal cognition and dementia. About 50%
of MCI subjects demonstrated significant deterioration of cognitive function and conversion to dementia within 5 years. Patients with depression
in late life also presented significant cognitive impairment (depressive
pseudodementia), and the prevalence on MCI symptoms is detected in
40-60% of these patients.
Method: The aim of this study was to assess cognitive frontal lobe dysfunctions in 30 non-depressed patients with Mild Cognitive Impairment
(MCI), comparing with age- gender- and education-matched 30 patients
with acute depressive episode, and with 30 healthy subjects.
Psychometric evaluation was done using Mini Mental State Examination
and Hamilton Depression Scale. Neuropsychological frontal lobe functions
assessment included Wisconsin Card Sorting Test (WCST) and the N-back
test.
Results: Patients with MCI obtained significantly worse results on all
domains of the WCST and the N-back test compared to both depressed
and healthy subjects. Depressed patients showed significantly worse performance than controls on most scores. In the MCI group, no association
with MMSE was found with any of WCST domains, neither with reaction
time in the N-back test.
Conclusion: The results obtained indicate significant frontal lobe impairment in patients with MCI compared to elderly depression and healthy
subjects and suggest a usefulness of employing WCST and N-back tests
for a neuropsychological evaluation of patients with MCI
References: 1.Morris JC: Mild cognitive impairment and preclinical
Alzheimers disease. Geriatrics 2005; Suppl 1: 9-14. 2.deMendonca A,
Ribeiro F, Guerreiro M, Garcia C: Frontotemporal Mild cognitive impairment. J Alzheimers Dis 2004; 6: 1-9. 3.Brassen S, Braus D, Weber-Fahr W,
Tost H, Moritz S, Adler G: Late-onset depression with mild cognitive
deficits: electrophysiological evidences for a preclinical dementia syndrome. Dement Geriatr Cognit Disord 2004; 18: 271-277. 4.Boone KB,
Lesser I, Miller B, Wohl M, Berman N, Lee A, Palmer B: Cognitive functioning in a mildly to moderately depressed geriatric sample: Relationship
to chronological age. J Neuropsychiatry Clin Neurosci 1994; 6: 267-272.
P-25-02
Long-term efficacy and safety of galantamine in outpatients with mild cognitive disorder
Julio Zarra
Hospital italiano de La Plata, Psiquiatria, Argentina
L.C. Schmidt
Introduction: galantamine is a reversible, competitive cholinesterasa
inhibitor that also allosterically modulates nicotine acetylcoline receptors.
Inhibition of acetylcholinesterase , the enzyme responsible for hydrolisis of
acetylcoline at the cholinergic cognitive impairment. To evaluate the efficacy, safety and tolerability of galantamine in long-term in Mild Cognitive
Disorder.
Methods: a multicenter , open label , prospective, observational study
enrolled 800 patients , more 50 years old with Mild Neurocognitive
Disorder (DSM IV criteria), during 24 months of treatment with galantamine 16 mg./day. Assessments included the Mini Mental State
Examination ( MMSE), Clinical Dementia Rating (CDR), Alzheimers
Disease Assessment Scale (ADAS-GOG), Seven minutes test, Wiscosin
card sorting test, Boston naming test, Token test, Raven Test, Brow-
130
Peterson test. Trail making test, Functional Activities Questionnaire (FAQ),

GO-NO-GO test, Global Deterioration Scale, Global Clinical Impression
(GCI) and UKU scale of Adverse Effects.
Results: a total 800 outpatiens were treated with 16 mg./day galantamine during 24 months , the therapeutic response evaluated with CDR ,
MMSE and the tests and scales of function cognitive measuring , GCI and
UKU scale of adverse effects, comparing the baseline to final scores .
Conclusion: Mild Cognitive Disorder is being examined , so there arent
enought treatment for this. A long-term treatment (24 months) galantamine improves cognition and golbal function , behavioral symptoms and
the general state well being of patients with Mild cognitive Disorder. With
incidence of adverse effects not significant and a very good profile of
safety, the final results of the study suggest that galantamine may be particulary appropiate in the Mild Cognitive Disorder.
References: Blesa R.: Galantamine:Therapeutic effects beyon Cognition.
Dement Geriatr Cogn Disord . 2000. 11 (suppl 1):28-34
P-25-03
Mild cognitive disorder and depression: Treatment with
association between galantamine and venlafaxine xr
Julio Zarra
Hospital italiano de La Plata, Psiquiatria, Argentina
Introduction: To evaluate the therapeutic response in patients with
comorbility between Mild Cognitive Disorder and Depression in treatment
with Galantamine , Venlafaxine XR and The two drugs associated.
Methods: A group of 270 patients with symptoms of Mild Cognitive
Disorder and Depression(DSM IV-R criteria)were separatedin 3 groups of
90. Each group received different treatment in a 8 months period: Group
1 : Galantamine 16 mg/day. Group 2 : Venlafaxine XR 75 mg/day. Group
3: both drugs , same dose.
Results: The therapeutic response evaluated in Hamilton Scale for
Depression(HAM-D), Montgomery and sberg Depression Rating Scale
(M.A.D.R.S.), Mini Mental State Examination (M.M.S.E.) and Global
Clinical Impression (G.C.I.) scores during 8 months in the third group who
received the two drugs associated, had much better response than the
others.
Conclusion: The group who received the association of the nootropic
agent Galantamine with antidepressant Venlafaxine XR had a relevant
satisfactory therapeutic response (the best result), so there is a possible
relation between the deficit in colinergic systems and depression. Could
be cerebral colinergic systems deficit a generator of Depressive Disorder?
References: Blesa R.: Galantamine:Therapeutic effects beyon Cognition.
Dement Geriatr Cogn Disord. 2000. 11 (suppl 1):28-34.Sramek JJ et al
2001: The status of ongoing trials for Mild Cognitive Impairment. Experts
Oping investing drugs. 10 (4):741-752.
P-25-04
Mild cognitive impairment prevalence in the more than 65
years old population
Piedad Medina
28 de Enero Policlinic, Psychiatry, Havana, Cuba
Introduction: Actually, is very important to have a precise diagnosis to
the Mild Cognitive Impairment, because, is the previous steep to
Alzheimers disease
Methods: There is a descriptive- concurrent research in all the population. The total population of the policlinic is composed by 1395 old men
and we applied a study at 1302 (94%) of them the remaining ones were
since outside of area or of the country. To all, we apply two different test:
Mini-mental State Examination (Folstein, Folstein and Mc Hugh) and
Clinical Dementia Rating to identify the normal mental health, the Mild
Cognitive Impairment and the Dementia.
Results: Looking for possible insanities finds that the population 72.7%
was classified as normal, 14,3% classified fundamentally as Alzheimer
disease and we find in this research that 13 % to the studied population
had Mild Cognitive Impairment, and of them, 98% presented alterations
in the memory, 48% in the attention, being also affected in smaller
degree the language understanding (30,6%) and the orientation in time
(6,25 %)
Conclusion: The studied population's mental health, bigger than

65 years, reaches a high index of normality, however, although the
patients with Mild Cognitive Impairment they have a normal life, early
presented alterations in the memory and attention fundamentally
References: -Morris J.C. The Clinical Dementia Rating (CDR): Current version and scoring rules. Neurology,1993; 43:2412-2414.-Folstein MF,
Folstein SE, Mchugh PR. Minimental state A practical method for grading the cognitive state of patient for de clinical J. Psychiatric. Res 1975;
12: 198-189-OMS 1994. Evaluacin de la Calidad de Vida. Por qu la
Calidad de Vida?. Grupo WHOQUOL. Foro Mundial de la Salud. Ginebra.Fdez, Y. Earliy detection of Alzheimers disease, Cuba-US Workshop on
Biological Psychiatry, La Habana, 2004.
P-25-05
Saccadic eye movements in dementia, major depression
and healthy controls
Hans-Juergen Schewe
Charite University Medicine, Department of Psychiatry, Berlin, Germany
Knut Vohs, Ralf Uebelhack
Introduction: Saccadic eye movements may be considered as a physiological marker of several psychiatric disorders. The present study aimed to
find a possible relationship between saccadic parameters to cognitive performance in patients.
Method: We investigated horizontal saccadic eye movements in 3 groups
of probands: patients with degenerative dementia, patients with major
depression and healthy controls. Saccadic eye movements were generated using a visual target moving with varying amplitude, frequency and
direction, measured by infrared reflection technique. Cognitive performance was examined using the Mini-Mental-State-Examination (MMSE)
and the ADAS-cog-Scale (patients with dementia) or a large neuropsychological test battery (depressed patients).
Results: Significant differences between healthy controls and patients
with dementia were found in 2 parameters of saccadic eye movement:
Latency (p<0.01) and number of saccadic intrusions (p<0.001). Saccadic
intrusions were defined as saccades leading the gaze away from the target by more than 3 during the periods of fixation. Saccadic parameters
latency (r= -0.68, p<0.05) and frequency of saccadic intrusions (r= -0.71,
p<0.05) correlated significantly with the MMSE-scores within the demential group. Also, there was a significant correlation between ADAS-cogscores and latency (r=0.64, p<0.05) and intrusions (r=0.58, p<0.05).
Considering ADAS-cog-subscales we found that subscale orientation
was most correlated with latency (r=0.70, p<0.05) and intrusions (r=0.71,
p<0.05). Patients with major depression and healthy controls showed no
significant differences in saccadic parameters. Moreover, no significant
correlation appeared between saccadic parameters and severity of cognitive deficits.
Conclusion: The results indicate that there are a strong correlation
between disturbance in saccadic eye movement and cognitive deficits in
patient with degenerative dementia, but not in depressed patients with
reduced cognitive performance. The measurment of saccadic eye movement might be suitable for the differentiation of pseudodementia in
depressed patients from degenerative dementia with depression.
P-25-06
Validity of the Korean version of the mini-cog
Youngmin Choi
Inje University, Sanggyepaik Hospt., Seoul, Republic of Korea
Methods: Mini-Cog, Mini-Mental Status Examination-Korean Version

(MMSE-KC), Short Blessed Test-Korean Version(SBT-K) and Clinical
Dementia Rating(CDR) were administered to 142 dementia patients and
140 elderly control groups. Cronbach alpha coefficient, test-retest reliability of Mini-Cog-K were examined. The correlations of MMSE-KC, SBT-K,
and CDR with Mini-Cog-K were also examined to confirm the validity of
the Mini-Cog. Cut-off scores for dementia were estimated by Receiver
Operator Characteristics(ROC) curve analyses. By Comparing Area Under
Curve(AUC), the diagnostic efficiency of Mini-Cog-K was compared with
those of MMSE-KC and SBT-K.
Results: 1) The Mini-Cog-K was found to have high internal consistency
(Cronbach alpha coefficient=0.94, P<0.01), and reasonable test-retest
reliability over 4 weeks(r=0.85, P<0.01). 2) The Mini-Cog correlated with
MMSE-KC, SBT-K, and CDR, which indicating Mini-Cog-K has good concurrent validity. Its optimal cut-off point for dementia was estimated as
13/14, and the sensitivity and the specificity at that point were 90.0%
and 95.8% respectively.
Conclusion: The Mini-Cog-K is reliable, valid, and probably very useful
screening test for dementia. And it is less time consuming than other
screening tools such as MMSE, it may be very convenient for the primary
care physicians.
References: Scanlan J.M.,, Borson S. 2001. The mini-cog: receiver operating characteristics with expert and nive raters. Int J Geriatr Psychiatry,
16:216-222
P-25-07
Cognitive function in patients with Alzheimers dementia
and concomitant cerebrovascular disease treated with
galantamine - a one year open-label phase-iiib study
Bernd Ibach
Janssen-Cilag GmbH, Medical & Scientific Affairs, Neuss, Germany
Martin Gerwe, Susanne Schwalen, Matthias Riepe
Introduction: Galantamine has been demonstrated to be effective and
generally safe in patients with Alzheimers disease and cerebrovascular
pathology (AD+CVD) in placebo-controlled trials. The aim of this openlabel clinical trial (GAL-GER-5) was to observe cognitive function during
long-term treatment with galantamine in patients with AD+CVD.
Method: Open-label, multi-center clinical trial (phase IIIb). Patients with
mild to moderate AD+CVD (meeting NINDS-AIREN criteria) received
galantamine (4-12 mg bid) for 12 months. Cognitive function was examined using the AKT (Alters-Konzentrations-Test) and DemTect.
Statistics were based on intent-to-treat population (LOCF, t-test and
Wilcoxon-test for dependent samples).
Results: 84 patients (43% with mild, 56% with moderate AD+CVD;
mean ageSD 75.56.8 years; 58% women) were enrolled. 80% of the
patients completed the study. Modal daily galantamine dose was 16mg
for 44%, and 24mg for 51% of the patients. After 12 months mean total
score in AKT showed a stabilization from 49.06.7 (baseline) to 49.26.9
(p=0.7807) and DemTect increased significantly from 7.82.0 to 9.43.9
(p<0.0001). CGI demonstrated an improvement or stabilization for 71%
of patients. 56% of the patients had at least one adverse event (AE). Most
frequent AEs with an incidence >5% were nausea and vomiting. 8
patients discontinued due to AEs. 21 patients experienced a SAE with 4
SAEs considered as possibly related to study medication (heart failure,
syncope, aggravated dementia, urinary retention).
Conclusion: This open-label study supports evidence from placebo-controlled trials of the efficacy and safety of galantamine in patients with
AD+CVD and suggests similar cognitive effects and safety through 12
months.
Introduction: In Korea, the mean time from the onset of first symptom
of dementia to first visit to clinic is about 2.7 years, much longer than the
developed countries. To improve the detection and referral rate, the development of rapid and easy-to- use screening tool which can be used routinely by primary care physicians is needed. The Mini-Cog is a rapid and
easy-to-use screening tool which can be used by primary care physicians.
The Mini-Cog uses a three-item recall test for memory and a simply
scored clock-drawing test. We conducted a study to validate a Korean
version of the Mini-Cog as a screening test for dementia which can be
used by primary care physicians.
131
P-25-08
Protective effects of eicosapentanoic acid (EPA) in MPP+
and MPTP- induced cell and animal models of Parkinsons
disease
Dirk Luchtman
Univ. of Prince Edward Island, Dep. of Biological Science, Charlottetown,
Canada
Cai Song
Introduction: The n-3 fatty acid, eicosapentaenoic acid (EPA) has been
shown to protect neurons in neurodegenerative disorders, possibly
through anti-oxidant and anti-inflammatory effects. Recent evidence suggests that inflammation and oxidative stress play an important role in
Parkinsons disease (PD). In the present study, we investigated whether
EPA has neuroprotective effects in cell and animal models of Parkinsons
disease.
Method: SH-SY5Y cells (dopaminergic neuron-like cells) were cultured,
differentiated and treated exclusively with parkinsonian neurotoxin
1-Methyl-4-phenylpyridinium iodide (MPP+) (0.01-1mM) for 24-48h to
induce direct cell toxicity and/or EPA (0.1- 200?M) for 48 hours to 6 days.
Cell viability was assessed by MTT assay. mRNA expression of cytosolic
phospholipase A2 (cPLA2), an important enzyme involved in membrane
fatty acid metabolism and inflammation, was determined with RT-PCR
technique. Twelve weeks old C57BL/6 mice were fed an 1% EPA /palm oil
(control) diet for 2 months, followed by 2 injections of parkinsonian neurotoxin 1-Methyl-4-(2-methylphenyl)-1,2,3,6-tetrahydropyridine hydrochloride (MPTP), 40mg/kg, i.p., or saline, 16 hours apart. Motor performance was assessed 3 hours and 1 week after MPTP/saline injections with
the Open Field and Rotarod. One or two-way analyses of variance and
post-hoc tests were applied to investigate all experimental treatments.
Results: MTT assays revealed a significant increase of cell viability after
EPA treatment, which was dose and time dependent. MPP+ caused a significant drop in cell viability in a dose and time dependent manner, which
could be partially or fully reversed by EPA treatment. cPLA2 mRNA expression was down-regulated significantly by EPA treatment. Chronic EPA
treatment significantly boosted motor learning performance in mice
during pre-training. Rotarod performance was only affected by MPTP
during the first days post injection, whereas a deficit of Open Field activity
could still be detected 1 week post injection in animals treated with
1% palm oil, but not in animals treated with 1% EPA.
Conclusion: Our findings suggest potential beneficial effects of EPA in
PD: 1) EPA increased viability and protected against a neurotoxic insult in
fully differentiated SH-SY5Y cells; 2) EPA downregulated cPLA2, which
could be beneficial in PD, as cPLA2 knock-out mice have been found earlier to be resistant to MPTP toxicity and 3) Overall motor learning performance was boosted by 1% EPA and EPA treated animals recovered quicker
from the MPTP-induced locomotor deficit in the Open Field than palm oil
treated controls.
P-25-09
The risk of progression in mild cognitive impairment:
Predictive role of plasma homocysteine
Tomasz Gabryelewicz
Polish Academy of Sciences, Degenerative Disorders, IMDiK, Warsaw,
Poland
Maria Styczynska, Beata Peplonska, Wojciech Androsiuk, Elzbieta
Luczywek, Anna Barczak, Boguslaw Wasiak, Anna Pfeffer, Malgorzata
Chodakowska-Zebrowska, Maria Barcikowska
Introduction: Mild cognitive impairment (MCI) is a condition referring to
the persons with cognitive deficits measurable in some form or another,
but not meeting criteria for dementia, and who have an increased risk of
becoming demented. The aim of this study was to establish the rate of
progression to dementia in MCI, to investigate the risk of progression for
different subtypes, and the features which discriminated between those
who progressed and those who did not.
Method: MCI (n=105) individuals enrolled in longitudinal study at an
Alzheimers Day Clinic in Warsaw received annual clinical and psychometric examinations for up to mean 3 years. Laboratory studies were performed, including concentration of plasma total homocysteine (tHcy). The
diagnosis of MCI according to Mayo Clinic Petersens Criteria was made
132
by the panel of specialists. 42 subjects were classified as amnestic MCI

and 63 as multiple-domain MCI with memory impairment.
Results: After 3 years of follow-up, 23 of 105 subjects with MCI were
diagnosed with dementia. 40 shoved cognitive decline not dementia, 34
were stabile, while 8 shoved cognitive improvement. The risk of conversion to dementia was higher among the subjects with multiple-domain
MCI. A moderately elevated plasma tHcy levels (14.3 mol/l; SD 4.2) were
observed in 60.95% of MCI sample compared with normal ranges. The
multiple-domain group had statistically higher mean plasma tHcy levels
then amnestic group (15.2 vs 12.8) , and the subjects who converted to
dementia had statistically significant higher baseline mean plasma tHcy
levels then non-converters (16.53 vs 14.36).
Conclusion: We conclude that the risk of conversion to dementia was
higher among the subjects with multiple-domain MCI than amnestic MCI,
and the occurrence of elevated plasma tHcy levels may constitute a predictor for those who are more likely to progress to dementia.
P-25-10
Frequency of delirium in elderly patients with hip fracture
Marcos Vaz de Lima
Santa Casa de Sao Paulo, Ortopedia, Brazil
Fabiana Benites, Claudia Freitas, Jose Octavio Soares Hungria
Introduction: Elderly patients with hip fracture may have some
perioperative complications, including Delirium, which can increase significantly the morbidity and mortality for these patients. The aim of this
study was to examine the frequency, the onset of the Delirium, risk
factors and the detection of symptons by the physician assistent and the
family.
Method: A longitudinal prospective study was made to diagnose
Delirium in three periods of hospitalization: in the admission, just before
the surgery and in the pos-operative. Risk factors and identification by the
family and the physician assistent were also evaluated.
Results: Forty-two percent of the patients developed symptons of
Delirium in one or more studied periods. Multiple medical problems,
metabolic disturbances, fever and few social interactions did not show
statistical significance association with the disease. Infection (RR=2,61,
p=0,001, e IC 95% (1,56-2,93)), psychoactive drug use (RR=2,11,
p=0,007 e IC 95% (1,201-3,877)), dementia (RR=1,78, p=0,003 e IC
95% (1,05-2,85)) and visual impairment (RR=2,19, p=0,004 e IC 95%
(1,54-11,16)) were associated with Delirium. 89% of the patients with
Delirium had their symptons recognized by the family, although, only
36% were recognized by the physician assistent.
Conclusion: The frequency of Delirium in elderly patients with hip fracture
was high. Risk factors were infection, psychoactive drug use, dementia
and visual impairment. The physician assistent failed in the diagnosis of
the Delirium.
References: 1. APA, American Psychiatric Association: Diagnostic and
Statistical Manual of Mental Disorders, (DSM-IV). 4th ed ed. 1994,
Washington, DC: APA. 2. Chan, D. and N.J. Brennan, Delirium: making
the diagnosis, improving the prognosis. Geriatrics, 1999. 54(3): p. 28-30,
36, 39-42. 3. Gotor, P., et al., [Delirium on hospitalized aged hip fracture
patients]. Med Clin (Barc), 2005. 125(12): p. 477-8; author reply 478-9.
4. Lipowski, Z.J., Delirium (acute confusional states). Jama, 1987.
258(13): p. 1789-92.
P-25-11
Polypharmacotherapy of rapid developing Alzheimers
dementia with psychotic symptoms
Miro Jakovljevic
Univ Hospital Zagreb, Psychiatry, Croatia
Bjanka Vuksan
Introduction: Drug monotherapy in patients with Alzheimers disease is
usually unsuccessful or only partially effective. Multiple medications from
different categories may be necessary for successful treatment.
Method: The case report describing a patient with rapid developing
dementia and psychotic symptoms treated with olanzapine, memantine,
donepezil and omega-3.
Results: Satisfying and long-term recovery was achieved rapidly. Before

drug treatment. Mini mental state egzam score was 17/30, three months
later 27/30, and after one year of treatment 24/30.
Conclusion: The prevailing fatalism and treatment nihilism with regards
to treatment of dementia should open way to more hope and optimism.
P-25-12
Cognitive impairment in spinocerebellar ataxia type 2
Jiri Masopust
Universital Hospital, Dpt. of Psychiatry, Hradec Kralove, Czech Republic
Ales Urban, Zuzana Rihova, Elen Urbanova, Martin Valis, Alena Zumrova
Introduction: Cerebellum is important in multiple functional domains:
motor, sensory, affective and cognitive. Autosomal dominant spinocerebellar ataxias (SCA) provide a useful model of cerebellar pathology in
studying the nonmotor functional deficits. SCA are clinically heterogenous group of neurodegenerative disorders with progressive ataxia that
results from degeneration of the cerebellum and its connections. Patients
with SCA2 may develop poor memory, concentration problems, impairments of conceptual reasoning, and frontal-executive dysfunction, as well
as emotional instability and impulsivity.
Method: We performed psychiatric, neuropsychological and functional
neuroimaging examinations in eight SCA2 patients. The following cognitive domains where assessed: executive functions, short-term visual and
verbal memory, attention, psychomotor speed, visuomotor coordination
and learning and intellectual ability. Regional cerebral flow (rCBF) was
measured in all patients by single photon emission computed tomography (SPECT). Perfusion abnormalities in various parts of brain including a
cerebellum were identified by visual analysis.
Results: We established psychiatric diagnosis in 7 patients with SCA2. In
most cases we diagnosed mild cognitive impairment, organic affective
disorder and organic personality disorder. Neuropsychological assessment
identified the impairment of executive functions such as set-shifting,
planning and verbal fluency, difficulties in visuomotor coordination,
deficit in all types of attention. Patients often failed cognitive tasks linked
to prefrontal cortex (such as verbal fluency, Wisconsin Card Sorting Test,
Tower of Hanoi). This findings correlated with results of SPECT. Severity of
the cognitive deficit correlated with the results of measurement of the
motor damage. This finding could have been caused by the small group
of our patients as well as motoric requirements of the neuropsychological
tasks. The examination by SPECT detected decreased rCBF in the cerebellum in 7 patients. Six of seven these patients had low rCBF in the left
frontal cortex by visual assessment.
Conclusion: Cognitive impairment in patients with SCA2 was particularly found in executive functions and attention. SPECT hypoperfusion was
detected in left frontal areas, in addition to cerebellum, in most patients.
These preliminary data support the notion that cerebellum is also associated with cognitive information processing and behavior. We can not
come to any large-scale conclusions because of small number of patients.
Due to a high motoric requirement of all used neuropsychologic tests, it
is difficult to distinguish between cognitive and motoric performance.
References: Schmahmann JD, Sherman JC. The cerebellar cognitive
affective syndrome. Brain 1998; 121: 561-579.
P-25-13
Learning and memory: Role of the postsynaptic 5-HT1A
receptor
Bettina Bert
Freie Universitt Berlin, Pharmacology & Toxikology, Germany
Jrg-Peter Voigt, Julia Rothe, Alexandra Wistel, Andre Rex, Heidrun Fink
Introduction: The serotonin 1A (5-HT1A) receptor is one of the best
described receptor subtypes of the serotonergic system, the complex distribution pattern, the pre- and postsynaptic localisation, and the impact
on various monoamines aggravate the attribution of 5-HT1A agonist
effects to behavioural outcomes. Here, a mouse line with a postsynaptic
over-expression of the 5-HT1A receptor in the dentate gyrus and outer
cortical layers is presented. Recently, it was shown that these mice displayed an exaggerated response to the 5-HT1A receptor agonist 8-OHDPAT concerning motor activity and body temperature (Bert et al. 2006).
Moreover, in the Porsolt swim test, an animal model for testing antidepressants, transgenic mice demonstrated antidepressant-like behaviour.
Method: In this study their learning and memory abilities were investigated in the Morris water maze and inhibitory avoidance test. Habituation
learning was studied in the hole board test conducted on two consecutive
days. The effects of 8-OH-DPAT (0.1-1.0 mg/kg i.p.) on learning and
memory were examined in the inhibitory avoidance test.
Results: The results indicate that transgenic mice have no overall cognitive deficit. They showed similar spatial learning abilities in the Morris
water maze test and habituated to the hole board in a comparable manner to wild-type mice. As a tendency, inhibitory avoidance retention was
impaired in 5-HT1A over-expressing mice in comparison to wild-type controls. However, anterograde amnesia induced by 8-OH-DPAT was in transgenic mice already apparent in a threefold lower dose of the agonist (0.3
mg/kg) compared to wild-type mice (1.0 mg/kg).
Conclusion: Since the 5-HT1A receptor over-expressing mice show
untreated a rather normal behaviour likewise to wild-type mice, we
assume that transgenic mice possess compensatory mechanisms.
However, after activation of the postsynaptic 5-HT1A receptors the differences between wild-type and transgenic mice became more obvious.
Hence, our findings suggest that postsynaptic 5-HT1A receptors in the
dentate gyrus and outer cortical layers play a modulatory role in learning.
References: Bert et al. Behav Brain Res 2006, 167(2):328-41
P-25-14
MMSE versus cognitive subsection of UHDRS correlated
with age and stage of illness
Karin Reisinger
Univ. Clinic of Psychiatry, Graz Medical University, Austria
Brigitte Herranhof, Anna Hdl, R.M. Bonelli
Introduction: The Unified Huntington Disease Rating Scale(UHDRS) is a
rating system to quantify the severity of Huntington disease (HD) in cognitive, behavioural, functional and motor subsections. Our study compared neuropsychological tests of cognitive subsection of UHDRS to Mini
Mental State Examination(MMSE) and its categories and correlate them
with age of patients and stages of illness.
Method: We investigated 110 HD-patients. In treatment of HD it`s
important to discriminate five stages of disease (I.Shoulsen) , as the clinical presentation of a patient is also influenced by stage of disease . A
specialist for psychiatry graded HD-patients (stage I - V) according to the
functional assessment scale (= HD functional capacity scale) and we
examined HD-patients using the UHDRS. We correlated neuropsychological tests of the cognitive subsection of UHDRS (Stroop 1, Stroop 2 , Stroop 3,
Symbol Digit Modility Test , Verbal fluency Test) with MMSE and its categories. We correlated each test with stage of illness and age too.
Results: The MMSE has in no category a correlation with stage of HD
and age of patients .This doesnt agree with the hypothesis that MMSE
is correlated with age and degree of schooling .The score of MMSE of all
our investigated patients is independent of age and stage of illness. The
average MMSE-score is 27,5 (0-24 = Dementia). Our results demonstrate
that classifying HD-patients only with MMSE does not reveal dementia.
Additional neuropsychological tests of UHDRS are very important. Stroop
Test 3 , Verbal fluency Test and Symbol digit modility test correlate with
stage of illness. We conclude that HD-patients loose selective attention in
higher stages of illness. The profit of MMSE is weak variability in patients
with HD, Category language use and comprehension has the weakest
variability, memory the highest one. Cognitive tests of UHDRS have a
high variability in patients with HD. There is a weak correlation between
MMSE and other cognitive tests except Stroop Test 2 . None of the test
correlated with age of patients with HD.
Conclusion: Our results clearly demonstrate that MMSE-score is independend from age. MMSE-score is independent from stage of illness. This
test isnt practical to describe the progress of a chronic illness like HD.
Additionally tests are necessary for dementiascreening in HD.MMSE is a
good screening test for dementia in Alzheimer disease but not for
Huntington because 16 of 30 points investigate the capacity of memory
and so the test is for HD not qualified.
133
P-25-15
Cognitive effects of a prolonged-release formulation of
galantamine (prc) in patients with alzheimers disease (ad)
- an open-label phase-iiib-study
Martin Gerwe
Janssen-Cilag Gmbh, Medical & Scientific Affairs, Neuss, Germany
Bernd Ibach, Joerg Czekalla, H.- J. Moeller
Introduction: Randomized controlled clinical trials have demonstrated
the efficacy of galantamine-PRC in the treatment of AD-patients.
Objectives of this clinical trial were to further study the overall effect of
galantamine-PRC on cognition and function in patients with AD.
Method: Open-label, multi-center clinical trial (GAL-DEM-3002). Patients
with mild to moderate AD (NINCDS-ADRDA criteria) received 16-24
mg/day galantamine-PRC for 6 months. Primary objectives were to examine
the effects on cognitive function using ADAS-cog and DemTect.
Response-rate at endpoint was defined as percentage of patients with
change in ADAS-cog<=0. Statistical analyses based on intent-to-treat
population (LOCF, t-test, Wilcoxon-test for dependent samples).
Results: 133 patients (48% with mild, 52% with moderate AD; mean
ageSD 75.47.8 years; 68% women) were enrolled with 71% of the
patients completing the study. 53% of the patients received 24mg/day
galantamine-PRC. After 6 months mean total scores changed significantly, both in ADAS-cog, from 23.39.3 (baseline) to 20.49.7 (p<0.0001)
and DemTect from 7.32.9 to 9.24.3 (p<0.0001). The response-rate was
64.2%. CGI demonstrated an improvement or stabilization for 83% of
patients. 64% of the patients had at least one adverse event (AE). Most
frequent AEs (>5%) were nausea, vomiting and headache. 28 patients
discontinued due to AEs. 15 patients experienced a serious AE with
3 SAEs thereof considered as possibly related to study medication (syncope, hypotension, agitation). 2 deaths (sudden death, renal failure) were
rated as unrelated to galantamine-PRC.
Conclusion: This clinical trial supports the evidence from placebo-controlled trials that galantamine-PRC is tolerated and effective in the treatment of AD-patients in a clinical setting.
134
PSYCHOTIC DISORDERS - Poster
P-04
Psychotic Disorders
P-04-01
Evaluation of the four-item negative symptom assessment
(nsa-4) scale in patients with schizophrenia
Larry Alphs
Pfizer Inc, Pfizer Global R&D, Ann Arbor, USA
Robert Morlock, Cheryl D. Hill, Pilar Cazorla, Jacquelyn Wilson, Scott
Lancaster
Introduction: The 16-item Negative Symptom Assessment scale (NSA16), which also includes a separate Global Rating, is a validated measure
of negative symptoms in schizophrenia. A 4-item version has been
designed for raters with minimal training to provide quick assessment of
patients with negative symptoms. We evaluated the psychometric properties of the NSA-4 for comparison with the NSA-16.
Method: The NSA-16 was administered at randomization in clinical trials
in patients (n=561) with predominant negative symptoms.
Coadministered measures included the Positive and Negative Syndrome
Scale (PANSS), Clinical Global Impression-Severity of Illness scale (CGI-S),
and Level of Functioning (LOF) assessment. The NSA-4 and NSA-16 were
compared for their ability to predict the NSA Global Rating and CGI-S.
Convergent and divergent validity were assessed using correlations
between the NSA-4 and NSA-16 and other outcomes measures. Internal
consistency and test-retest reliability of the NSA-4 and NSA-16 were also
compared.
Results: NSA-4 showed high correlation with NSA-16 (r = 0.85,
P<0.0001). Both instruments showed similar high correlation with the
NSA Global Rating (r=0.71 for NSA-16 and r=0.70 for NSA-4, both
P<0.0001), PANSS negative factor (Marder) score (r=0.63 and r=0.57,
P<0.0001), PANSS negative symptoms subscale score (r=0.59 and r=0.52,
P<0.0001), and LOF (r= ?0.51 and r= ?0.47, P<0.0001). Both the NSA-4
and NSA-16 were predictive of severity classifications as determined by
the NSA Global Rating and CGI-S (P<0.0001). Internal consistency was
0.85 for NSA-16 and 0.64 for NSA-4 (decrease would be expected for a
4 item scale measuring multiple domains). The test-retest intraclass correlation coefficient was 0.87 for NSA-16 and 0.82 for NSA-4 (both adequate).
Conclusion: The NSA-4 and NSA-16 both demonstrate acceptable psychometric properties for assessing the level of impairment associated with
negative symptoms in patients with schizophrenia. The NSA-4 is an easyto-use tool that can be used in clinical practice for quick assessment and
tracking of negative symptoms.
P-04-02
Insight as a predicting factor in the early phases of schizophrenia (eiffel project)
Miguel Gutierrez
Baracaldo, Spain
Rafael Segarra Gutierrez, Inaki Eguiluz, Alexander Rodrguez, Carmen
Castillo, Iban Ruiz
Introduction: Insight in schizophrenia shows critical implications for
adherence. Non-adherence is particularly relevant in first-episode
patients. Few studies have examined insight in early schizophrenia. The
aim of this study is to examine relationship between insight, adherence
and outcome in patients with early schizophrenia.
Method: Observational study in patients diagnosed for schizophrenia,
schizophreniform, or schizoaffective disorder for less than 5 years. Data
are collected retrospectively from first psychotic episode to study start,
and prospectively (1 year). Association of demographic data, clinical
measures, remission, relapses, and adherence with level of insight (Scale
to Assess Unawareness of Mental Disorder and G12 item of PANSS) was
evaluated. Adherence was assessed interviewing patients and family.
Remission was defined according to Remission in Schizophrenia Working
Group criteria. Preliminary data are shown.
Results: 575 patients have been analyzed. Duration of illness was

3.91.6 years. According to G12 item of PANSS, almost 50% of patients
had moderate to extreme impairment in baseline insight, while this percentage was 15.8% at 12 mo. (N=291). At baseline, 50% of patients
showed good adherence to medication (>80%), and adherence rose to
78% at 12 mo. (N=291). Remission (severity criteria) significantly
increased from baseline (23.9%, N=574) to 12 mo. (59.5%, N=291;
p<0.0001). A significant relationship between insight and remission at
baseline (p<0.001) was found. Among patients who reached 12 mo. visit
(N=289), hospitalization was more frequent in those with poor baseline
insight
Conclusion: Lack of insight is common in early schizophrenia and may be
a relevant predictor of poor outcome.
References: -Amador XF, Strauss DH, et al. Assesment of insight in psychosis. Am J Psychiatry 1993;150:873-9 -Coldham EL, Addington J,
Addington D.Medication adherence of individuals with a first episode of
psychosis. Acta Psychiatr Scand.2002 Oct;106(4):286-90
P-04-03
Pathways to care in a sample of patients with first-episode
psychosis (FEP)
Nilufar Mossaheb
Monika Schloegelhofer, Sonja Werneck-Rohrer, Rainer Kaufmann,
Harald Aschauer, G. Paul Amminger
Introduction: Pathways to care in emerging psychoses often involve long
durations of untreated psychosis and several help-seeking contacts before
adequate treatment (Singh et al. 2006, Skeate et al. 2002). Due to lack
of early recognition, early referral as well as fear of stigmatization,
patients do not reach specialized treatment possibilities for longer periods
of time. We report demographic data and pathways to care in a sample
of FEP patients recruited for the multi-centre Cognitive-Behavioral-CaseManagement trial at the Vienna site.
Method: In- and outpatients with FEP entering the Departments of
General Psychiatry and of Child and Adolescent Neuropsychiatry, Medical
University Vienna since March 2006 were screened. Patients with a FEP
with scores on BPRS (Brief Psychiatric Rating Scale)-items suspiciousness,
hallucinations, unusual thought content or conceptual disorganization of
at least 4 and not more than 6 months of antipsychotic treatment for psychosis were included. Pathways to care were assessed with the CORS
(Circumstances of Onset or Relapse Schedule) questionnaire and a clinical
interview. Preliminary data on demographics and pathways to care are
presented.
Results: Within a period of 8 months 31 patients were screened, 12 fulfilled inclusion criteria and gave informed consent after a mean of 24.3
(SD 7.2) days in our service. 41.7% of patients were female, mean age
was 20.3 years (SD 4.6). Patients reported a mean of 158.9 (SD 262.6)
days from first thought of need for help to actual first help-seeking contact. A mean number of 2.75 (SD1.1) contacts were sought until referral
to our trial. Types of contacts were variable ranging from general practitioners and other medical services over psychologists to kinesiologist.
Conclusion: We report preliminary data on demographics and pathways
to care in a sample of FEP patients included in a FEP-specific trial. As in
the literature, patients show long durations between first thought of
need for help and actual help-seeking contacts, as well as several contacts
until specialized treatment for FEP.
References: Singh SP, Grange T. Measuring pathsways to care in firstepisode psychosis: A systematic review. Schizophrenia Res 81 (2006): 7582 Skeate A, Jackson C, Birchwood M, Jones C. Duration of untreated
psychosis and pathways to care in first-episode psychosis. Br J Psychiatry
181 (Suppl. 43)(2002): s73-s77
135
P-04-04
Schizophrenia outcome: Need for psychosocial assessment
Amresh Shrivastava
University of Western Ontario, London, Ontario, Canada
Nilesh Shah, Meghana Thakar
Introduction: Numbers of studies have looked at the clinical outcome in
patient of schizophrenia. The emphasis is on improvement in clinical features with a particular antipsychotic medication. The improvement is usually
primarily assessed by looking at the fall in scores on PANSS and CGIS. Most
of these studies are of 8-12 weeks duration and report a short-term outcome. It is now realized that along with the clinical outcome one should
also assess the improvement on various psychosocial measures as clinical
improvement may not give the clear picture of the extent of recovery. It is
also stressed that in the disorders like schizophrenia it is important to look
at the long-term outcome. So the present study was envisaged with the
intention to study the clinical as well psychosocial outcome at the end of
one year in patients of schizophrenia with risperidone therapy.
Method: Fifty consecutive patients of schizophrenia, diagnosed as per
the DSM-IV criteria, fulfilling the selection criteria were followed-up and
treated with risperidone over a period of one year. Improvement was
assessed using PANSS, CGIS and seven psychosocial parameters viz. social
functioning, productivity, economic independence, education, suicidality,
rehospitalization and exacerbation. Well defined operational criteria were
used to rate the patients on these seven psychosocial parameters.
Results: A statistically significant improvement was noticed with risperidone therapy on PANSS and CGIS at the end of study period of one year.
This was associated with a clinically significant improvement on all the
various psychosocial parameters.
Conclusion: A significant improvement is observed on clinical as well as
psychosocial parameters in the patients of schizophrenia over a period of
one year with risperidone therapy.
P-04-05
Face recognition and theory of mind in patients with
schizophrenia
Christine-Vanessa Cuervo
Hpital Robert Debr, Psychiatrie des adultes, Reims, France
Adeline Tisseron, Chrystele Besche-Richard, Fabien Gierski, Frederic
Limosin
Introduction: Theory of mind (ToM) means the ability to represent
others intentions, knowledge and beliefs; and interpret them. This study
examined the relationship between emotion recognition from facial
expressions and ToM in schizophrenia. We hypothesized that the difficulties in facial recognition of emotions in patients with schizophrenia could
modulate their capacities to recognize the mental states.
Method: Twenty schizophrenics patients and thirty controls subjects,
matched by age an education level, were included in the study. Four sets
of pictures depicting ToM stories, two first order and two second-orders
stories, were used. Recognition of emotions from facial expressions was
also assessed
Results: Statistical analysis showed significant differences between schizophrenics patients and controls subjects in all ToM stories and the recognition of emotions, with patients performing worse than controls subjects
(all ps<.05). For instance, patients performances were higher for firstorder stories. Finally, psychopathology severity, reflected by the Positive
and Negative Syndrome Scale (PANSS), was correlated with ToM scores.
Conclusion: Face recognition deficits and ToM deficits in schizophrenia
are apparent. Our results suggests that a deficit in the comprehension of
emotions is associated with a deficit in recognizing mental states in those
patients, more particularly for the one with prevalent negative symptoms.
Both deficits can explained the alterations of the social behavior in
patients with schizophrenia.
References: Brune M. (2005). Emotion recognition, theory of mind
and social behavior in schizophrenia. Psychiatry Research; 133, 135-147.
Frith CD. (2004). Schizophrenia and theory of mind. Psychological
Medecine 34, 385-389. Sachs G, Steger-Wuchse D, Kryspin-Exner I, Gur
RC, Katschnig H. (2004). Facial recognition deficits and cognition in schizophrenia. Schizophrenia Research 68, 27-35.
136
P-04-06
Impact of attention disorders on facial emotion recognition in patients with schizophrenia
Fabien Gierski
Hpital Robert Debr, Psychiatrie des adultes, Reims, France
Florian Faradoni, Chrystle Besche-Richard, Christine-Vanessa Cuervo,
Frederic Limosin
Introduction: It is now well known that patients with schizophrenia have
difficulties in facial recognition of emotions. However there is still considerable debate about the nature of the underlying deficit. We hypothesized that it could be accounted in a part for by attention disorders, which
are a core feature of cognitive disorders in schizophrenia. The aim of the
present study was to investigate this hypothesis by studying the effect of
speed of information processing in a facial emotion recognition task.
Method: Fifteen schizophrenic patients were compared to fifteen controls subjects, matched in terms of age, gender and education level, in a
choice reaction time task (CRT) and a facial emotion recognition task
(FER). In the CRT task participants were told to press a button according
to four different shapes (triangle, rectangle, oval, rhombus). In the FER
task they were told to state whether presented faces expressed one of
four possible emotions (happiness, fear, anger, sadness). Discriminability
and reaction time were computed for each tasks. Visual scanning accuracy
and speed were also assessed with the d2 test of attention.
Results: As expected, patients with schizophrenia were impaired in CRT
and the FER tasks, and for all emotions. However, when taking into
account speed of information processing, patients were only impaired in
the discrimination of fear and anger. Moreover, poorer performance in
emotion discrimination was correlated with lower d2 scores and with the
severity of negative symptoms.
Conclusion: Schizophrenic patients perform poorly when recognizing
facial expressions of emotion, particularly negative emotions such as fear
and anger; this finding has been taken as evidence of a negative emotion specific deficit. The alternative explanation supported by this study,
is that greater difficulty in recognizing negative emotions may reflect the
attention disorders of these patients.
References: Bediou B, Franck N, Saoud M, Baudouin JY, Tiberghien G,
Dalery J, dAmato T.(2005) Effects of emotion and identity on facial affect
processing in schizophrenia. Psychiatry Research; 133(2-3): 149-157.
Wang K, Fan J, Dong Y, Wang CQ, Lee TM, Posner MI. (2005). Selective
impairment of attentional networks of orienting and executive control in
schizophrenia. Schizophrenia Research; 78(2-3): 235-241. Bates ME,
Lemay EP Jr. (2004). The d2 Test of attention: construct validity and extensions in scoring techniques. Journal of the International
Neuropsychological Society; 10(3): 392-400.
P-04-07
Determination of predictors of clinical outcome, social and
ocupational performance in patients with First Episode
Psychosis: A key for prognosis optimization
Marco Fierro
CISNE, Psychiatry, Bogot D.C., Colombia
Rodrigo Nel Cordoba, Juan Fernando Cano, Claudia Rocio Vanegas,
Ricardo Cendales, Monica Olmos, Ana Olarte
Introduction: First Episode Psychosis(FEP), in many times, is the beginning of schizophrenia. Identifying warning potentials of their result are
one of the most novel themes in the psychiatry. Objective: Establishing
the predictive factors in the outcome after a year, in patients with First
Episode Psychosis attended in the psychiatric services in Hospital
Occidente Kennedy, Campo Abierto Clinic, and Hospital Santa Clara in
Bogot between February 1, 2004 and August 1, 2006.
Method: Multicentric, analytic, prospective, trial. The clinical characteristics, quality of life and, social and work operation is assessed with the
scales PANSS, BPRS, CGI, GAF, QLS, and MCAS. Exposition to the next
conditions is identified: socioeconomics and demographic features, personal and familiars antecedents, psychoactive substances use, duration of
prodrome of psychosis, and duration of untreated psychosis (DUP). One
year of follow up, with weekly visits the first month, every two weeks for
the second month, and then monthly.
Results: At first visit none of the explored variables was found to be associated with the clinical severity. To the presentation date the complete
results will be available.
Conclusion: FEP In some cases it is once in a life time episode, but in the
rest of them it points the establishment of a chronic psychotic disorder
like schizophrenia. It is impossible affirming with certainty which cases
will evolve as an only episode and which one will end as a chronic condition; nevertheless several clinic trials report some factors which may suggest the final outcome. In this trial we have found so far some issues as
DUP, level of premorbid adjustment, presence or predominance of negative symptoms, comorbid consume of psychoactive substances and social
issues; are the most related conditions with prognosis.
References: Robinson DG, Woerner MG, McMeniman M, Mendelowitz
A, Bilder RM. Symptomatic and functional recovery from a first episode of
schizophrenia or schizoaffective disorder. Am J Psychiatry 2004
Mar;161(3):473-9. Singh SP, Croudace T, Amin S, Kwiecinski R, Medley I,
Jones PB, et al. Three-year outcome of first-episode psychoses in an established community psychiatric service. Br J Psychiatry 2000 Mar;176:210-6.
Zhang-Wong J, Beiser M, Bean G, Iacono WG. Five-year course of schizophreniform disorder. Psychiatry Res 1995 Nov 29;59(1-2):109-17.
Pillmann F, Haring A, Balzuweit S, Marneros A. A comparison of DSM-IV
brief psychotic disorder with positive schizophrenia and healthy controls. Compr Psychiatry 2002 Sep;43(5):385-92.
P-04-08
Electro convulsive therapy in treatment-resistant schizophrenia
John Enterman
Parnassia, Psychiatrie, The Hague, Netherlands
Erik Hoencamp, Mark van der Gaag
Introduction: ECT is a treatment for schizophrenia that is relatively
underrated, although it has a definite place in the treatment of depression. 70% of sufferers from schizophrenia can be helped with antipsychotic medication and half of the remaining 30% can be successfully
treated with clozapine. The remaining 15% are treatment resistant, and
as yet have no evidence-based treatment option. Costs to the community and to patients, both in terms of money and in terms of quality of life,
are tremendous. This research project will attempt to secure the evidence
base needed to introduce ECT as a viable treatment for the latter group
of patients.
Method: In a double-blind randomized controlled trial conceived as an
add-on treatment for persons with treatment-resistant schizophrenia,
after having given informed consent, 40 subjects will receive ECT; another
40 will receive sham-ECT. A maximum of 24 biweekly treatments will be
administered. A comprehensive assessment will be done at baseline and
after every sixth treatment session, with the score on the Positive And
Negative Syndrome Scale as the primary outcome measure. Failure to
improve from one assessment to the next will result in entering the follow-up. A follow-up of one year will be done to achieve an impression of
the need for continuation or booster therapy. Results on the PANSS score
will be analyzed using Multivariate ANalysis Of Variables.
Results: No interim analysis of the results will be made. Results will be
presented to the international scientific community, both in written and
oral form. At the time of writing, the second patient has been included
Conclusion: This exiting research is now under way!
References: Kho, K.H., Blansjaar, B.A., de Vries, S., Babuskova, D.,
Zwinderman, A.H., Linszen, D.H., Electroconvulsive treatment of clozapine nonresponders suffering from schizophrenia: an open label study.
European Archives of Psychiatry and Clinical Neuroscience (2004); 12
Tharyan, P., Adams, C.E., Electroconvulsive therapy for schizophrenia
(Cochrane review) Abstract. http://www.update-software.com/abstracts/
ab000076.htm
P-04-09
Psychopathology in schizophrenia and personality disorders
Manuel Henry
University of La Laguna, Internal Medicine & Psychiatry, Tenerife, Spain
Armando L. Morena, Antonio Garcia-Hernandez, Estefania Diaz,
Aranzazu Orozco, Tania Rodriguez-Martos, Marta Martin, Francisco
Trujillo, Josue Monzon, Lourdes Fernandez, Ramon Gracia
Introduction: Introduction: The relationship between personality disorders and psychopathology in schizophrenia is not well known. Our aim
consists in investigating personality disorders and its relationship with psychopathology in a sample of adult schizophrenic patients under psychiatric treatment in a general hospital health setting.
Method: Methods: 37 adult paranoid schizophrenic patients undergoing
treatment in the University Hospital of the Canary Islands with DSM-IV
diagnosis of paranoid schizophrenia are included. Years from onset 9.20
s.d. 6.29, age at onset 19.75 s.d. 4.73. The record of personality disorders as a secondary diagnosis in the medical chart was taking into
account. The PANSS was applied for assessing positive, negative and
general psychopathology.
Results: Results: In 21 patients (56.7%) a personality disorder, mainly
with paranoid and schizotypal traits, was registered. The percentage of
each personality disorder is as follows, Schizotypal (16.2%), Paranoid
(13.5%), Schizoid (2.7%), Paranoid and Schizotypal (24.3%).The results
point to significant differences in psychopathology according to the
General Positive Symptoms scale indicating that Schizotypal patients
show less positive symptoms than those patients with a combined
Schizotypal and Paranoid pattern (p<.05). There are no significant differences between Schizotypal and Paranoid subgroups as well as between
Schizotypal and the Without Disorders group. There are no significant
differences between patients with both disorders (Schizotypal and
Paranoid) and the Paranoid and the Without Disorder groups. Further
analysis concerning individual symptoms of the Positive scale shows that
delusions, hallucinatory behaviour and suspiciousness had a lower score
in Schizotypal and the Without Disorders group than the Paranoid and
the Mixed group (p<.01). Hallucinatory Behaviour had a lower score in
Schizotypal and in the Without Disorder group compared to the Mixed
group but not compared to the Paranoid subgroup (p<.05).
Suspiciousness rated significantly lower in the Without group compared
to the Paranoid one (p<.05), but not compared to the other groups
Conclusion: Conclusions: Personality disorders in schizophrenia are not
uncommon. Specific personality disorders show specific profiles of psychopathology. More research is needed in order to open new avenues
about the relationship between personality disorders and psychopathology
in schizophrenia.
P-04-10
Encoding and maintenance impairments in spatial working
memory of schizophrenia
Chang Kyu Shin
Daegu Mental Hospital, Psychiatry, Daegu Metropolitan City, Republic of
Korea
Ik-Seung Chee, Yeon-Jung Woo
Introduction: This study was intended to investigate the process where
working memory impairments in schzophrenia occurs. In this study, working memory was considered as a system or mechanism where information is encoded, maintained, and updated for a short period of time.
Method: Schizophrenic group and normal control group performed computerized spatial working memory task. Schizophtenic group was divided
into two groups: the remission group and the non-remission group, each
of which has 12 subjects, using PANSS in order to examine the performance differences beween the incidence of remission of schizophrenic
symptom. And a control group consists of 12 normal participants of the
same age, years of education, and gender with schizophrenic group.
Results: The results indicated that the non-remission group exhibited statistically significant differences relative to the remission group and the
normal control group, but there was no significant differences for the
encoding of spatial working memory between the remission group and
the normal control group. And both the remission group and the nonremission group exhibited statistically significant differences from the nor-
137
mal control group for the maintenance of spatial working memory irrespective of encoding condition.
Conclusion: The spatial working memory impairments of schizophrenics
are due primarily to the encoding and mainmtenance of spatial working
memory. It was also supported that spatial working memory impairments
could be an endophenotype of schizophrenia based on the facts that the
remission group exhibited impairment at the maintenance of spatial
working memory.
References: Andreasen, N. C., Carpenter, W. C., Kane, J. M., Lasser,
R. A., & Weinberger, D. R. (2005). Remission in schizophrenia : Proposed
criteria and rationale for consensus. American Journal of Psychiatry, 162,
441-449. Barch, D. M., Sheline, Y. I., Csernansky, J. G., & Snyder, A. Z.
(2003) . Working memory and prefrontal cortex dysfunction : Specificity
to schizophrenia compared with major depression. Biological Psychiatry,
53, 376-384. Gold, J. M., Wilk, C. M., McMahon, R. P., Buchanan, R. W.,
& Luck, S. J. (2003). Working memory for visual features and conjunctions
in schizophrenia. Journal of Abnormal Psychology, 112, 61-71. Park, S.,
Puschel, J., Sauter, B., Rentsch, M., & Hell, D. (2002). Visual object working memory function and clinical symptoms in schizophrenia.
Schizophrenia Research, 59, 261-268.
P-04-11
Duration of untreated psychosis and its effect on the
course of schizophrenia
Brigita Novak Sarotar
University Psychiatric Hospita, Ljubljana, Slovenia
Bojana Avgustin, Marjeta Blinc, Marga Kocmur, Mark Agius
Introduction: The course and outcome of schizophrenia are influenced
by many factors; one of which is the duration of untreated psychosis
(DUP). A longer DUP is associated with poorer prognosis. Aim of the study
was to test the influence of DUP on the long-term course and severity of
schizophrenia; to test the hypothesis that early treatment with antipsychotics improves the outcome; to compare short and long-term outcome
in patients with a DUP longer than 1 year (group 1) with patients who had
been treated in the prodromal phase of the disease (group 0).
Method: 87 patients with schizophrenia were included to the retrospective study, 37 patients comprised group 0 and 50 patients comprised
group 1. The course and outcome of the disease was studied in the two
groups. The symptom severity was evaluated using a check list developed
from Comprehensive Assessment of At Risk Mental States (CAARMS)
inventory; the average daily dose of antipsychotics was calculated as well
as the number and duration of hospital admissions; sociodemographic
parameters evaluated included educational level achieved, employment
and marital status. Groups were compared during the first psychotic
episode and at the conclusion of the study.
Results: More symptoms of greater intensity were present during both
evaluations in group 1 as compared to group 0 patients. The patients in
group 0 needed lower dosages of antipsychotics even several years after
treatment had been initiated. This effect persisted until the final evaluation; 11% were without antipsychotics at the conclusion of the study.
Patients in group 1 were hospitalized more frequently; they needed more
hospitalizations and these were of longer duration. Only 38% of patients
in group 0 were treated in the hospital, 27% were hospitalized only once.
The vocational status was worse in group 1 patients with higher degree
of unemployment and disability. There were more single patients in group
1 during both evaluations.
Conclusion: DUP is associated with the course and severity of schizophrenia. Better outcome of the disease can be achieved with early treatment with antipsychotics. The effects on psychopathological symptom
severity, in daily antipsychotic dosages, in number and duration of hospitalizations and in many sociodemographic parameters were all shown to
be statistically significant.
138
P-04-12
Emotion recognition and the risk of early transition to psychosis in ultra-high risk individuals
Monika Schloegelhofer
University Hosp. f. Psychiatry, Dep. of General Psychiatry, Vienna, Austria
Miriam Schfer, Kostas Papageorgiou, Jana Becker, Nilufar Mossaheb,
Paul Amminger
Introduction: Problems in the perception of emotional material, in particular deficits in the recognition of fear and sadness, have been demonstrated in first-episode schizophrenia (Edwards et al, 2001). It is unknown
if affect perception deficits predate illness onset, and if such deficits predict transition to psychosis in individuals with subthreshold psychotic
symptoms.
Method: We examined the capacity to recognize facially expressed emotion and affective prosody recognition in 38 individuals at ultra-high risk
(UHR) for psychosis (according to criteria of Yung et al., 1998) (mean
age=16.1, SD=1.7 years) and 30 unaffected normal comparisons (NC)
(mean age=15.6, SD=2.0 years). UHR individuals received state-of-art
non-neuroleptic treatment. Clinical status regarding transition to psychosis was evaluated 12 weeks after baseline. Psychopathology was
assessed using the PANSS and the SCID-IV. Facial tasks were computerised
modifications of the Feinberg et al. (1986) procedure. Prosody tasks were
developed by Edwards et al. using four professional actors. Emotion
expressions included fear, sadness, surprise, anger, and neutral.
Students t-tests were used to compare summary scores across communication channels, facial affect and affective prosody recognition, for each
assessed emotion.
Results: At baseline the UHR group was characterized by a significant
deficit for the recognition of sadness as compared to the NC group. At
12-week follow up 8 (22.2%) UHR individuals were found psychotic. A
deficit for the recognition of neutral was associated with transition to
psychosis.
Conclusion: Specific emotion recognition deficits can be observed in
UHR individuals. Emotion recognition warrants further investigation in
UHR populations
References: Edwards, J., Pattison, P. E., Jackson, H. J., et al. Facial affect
and affective prosody recognition in first-episode schizophrenia.
Schizophr Res (2001) 48:235-53 Feinberg TE., Rifkin A., Schaffer C.,
Walker E. (1986) Facial discrimination and emotional recognition in
schizophrenia and affective disorders. Arch Gen Psychiatry. 1986
Mar;43(3):276-9.
P-04-13
Evaluation of magnocellular pathway dysfunction in
schizophrenia
Fabiana Benites
Universidade Federal de Sao Paulo (UNIFESP), Brazil
Carolina Barbosa, Luciana Porto da Nobrega, Augusto Paranhos Jr.,
Rodrigo Afonseca Bressan
Introduction: Visual processing deficits have been reported for patients
with schizophrenia. The study of early-stage visual processing is important
because deficits in this system can produce lack of information to the
visual cortex which can result in clinical symptoms for patients,for example, deficits in selective and sustained attention (vigilance), and disturbances of visual memory. Previous studies have demonstrated that there
are differences in the early-stage processing of schizophrenia, although
the nature, extent and localization of the disturbance are still unknown.
It has been found that visual pathways M (magnocellular) and P (parvocellular) are associated with transient and sustained channels. Some studies proposed that the deficit in schizophrenia is in M pathway or transient channels. Other studies showed that the deficit is in P pathway or
sustained channels or even in the abnormal interaction between magno
and parvocellular channels. The aim of this study was to evaluate the
magnocellular dysfunction in schizophrenia by utilizing the frequency
doubling technology (FDT).
Method: Twenty DSM- IV schizophrenic patients29 healthy volunteers
were examined. Subjects were excluded if they met criteria for alcohol or
substance dependence or had any neurological or ophthalmologic disorder that might affect their performance. FDT testing was performed in
one session. First was used the screening strategy and 15 minutes later
the C-20 program for FDT. The stimuli have a sinusoidal pattern with frequency of 50 Hz.
Results: Schizophrenia patients showed a lower general sensitivity mean
(30,97dB2,25) in comparison with the control group mean (32,17dB
3,08), but this difference was not statistically significant Fovea sensitivity was different (-1,613,14dB for patients versus -0,451,77dB for controls),(p = 0,055; power = 0,48). There was no difference in the delta of
hemispheres between patients and controls, although the right hemisphere sensitivity was lower in patients (mean -0,261,32dB) in comparison to control group (mean 0,121,02dB), without statistical significance. There was no association between the positive-negative symptoms
and general MD, foveal MD and the difference between the hemispheres
(p > 0,05).
Conclusion: These preliminary results suggest that there are small differences between global sensitivity and hemisphere sensitivity measured by
FDT. However, a larger sample size is required to evaluate the dysfunction
in magnocellular pathways hypothesis.The present findings contribute to
a significant body of research to assess early-stage visual processing
deficits for patients with schizophrenia.
P-04-14
Catechol-O-Methyltransferase gene polymorphism
(Valine/Methionine) associated neither with schizophrenia
nor with bipolar disorder in a Korean population
Ik-Seung Chee
Chungnam National University, Psychiatry, Daejon, Republic of Korea
Lee Sun-Woo, Kim Jeon Lan, Wang Seung-Keun, Kim Myeung-Soo
Introduction: Catechol-O-methyltransferase(COMT) is an important
enzyme that inactivates biologically active or toxic catechols. Abnormal
catecholamine transmission has been implicated in the pathogenesis of
schizophrenia and bipolar disorder. Polymorphism(Val/Met) of the COMT
gene was shown to determine high-and low -activity alleles of the
enzyme. This study was designed to investigate the association between
COMT gene polymorphism and schizophrenia and bipolar disorder in a
Korean Population
Method: COMT gene were genotyped with polymerase chain reaction
and restriction enzyme NlaIII in 128 patientes with schizophrenia, 110
with bipolar disorder, and 176 controls.
Results: 1.The distribution of the COMT genotype in schizophrenic
patients with Val/Val, Val/Met, Met/Met were 76 (59.4%), 43 (33.6%),
9 (7.0%), in bipolar disorder patients were 63 (57.3%) 35 (31.8%)
12 (10.9%), and in the controls were 83 (47.2%) 79 (44.9%) 14 (8.0%).
The allele frequencies of the COMT gene in schizophrenics with Val and
Met were 195 (76.2%), 61 (23.8), in bipolar disorders were 161 (73.2%)
59 (26.8%), and in the controls were 245 (69.6%) 107 (30.4%) 2. There
were no differences in genotype distribution and allele frequencies of
COMT gene polymorphism among the 3 groups. Neither patients with
schizophrenia nor bipolar disorder differed in the genotype and allelic frequencies from the controls.
Conclusion: These results suggest COMT gene polymorphism (Val/Met)
is not causally related to the development of schizophrenia and bipolar
disorder in a Korean Population
References: 1. Lachman HM, Papolos DF, Saito T,et al(1996).Human
catechol-0-methyltrasferase pharmacogenetics:description of functional
polymorphism and it potential application to neuropsychiatric
disorders.Pharmacogenetics6:243-250 2. Strouss RD, Bark N, Woerner M,
et al(1997).Lack of association of a functional catecholamine-o-methyltransferase gene polymorphism in schizophrenia. Biol Psychiatry 41: 493495 3.Biomed European Bipolar Collaborative Group (1997). No association between bipolar disorder and alleles at a functional polymorphism
in the COMT gene. Br J Psychiatry 170: 526-528.
P-04-15
Cross-modal attention capture in schizophrenia
Matthew Kean
Lancaster University, Psychology Department, United Kingdom
Ulrich Ettinger, Veena Kumari, Steven Williams, Anantah Anilkumar,
Trevor Crawford
Introduction: One cognitive feature of schizophrenia (SZ) is a deficit in

the ability to disengage attention from salient events in peripheral vision
(Maruff et al., 1998). We investigated whether an analogous attention
deficit might occur in SZ in the auditory sensory modality; i.e., whether
individuals with SZ may experience a difficulty shifting attention away
from the location of a sound.
Method: We used a technique similar to Posners (1980) spatial cueing
paradigm, but with peripheral auditory cues and visual targets. The target
could be presented either ipsilateral or contralateral to the spatial location
from which the cue had sounded 200 ms prior, and participants executed
a saccadic eye movement to the target. Three conditions varied the probability of the target appearing ipsilateral to the cue (20%, 50%, and 80%
target-at-cue (TAC) conditions). Saccadic latencies were subjected to an
ANOVA with 2 repeated measures factors (Validity and Condition), and
with Group (SZ vs. controls) as a between-groups measure.
Results: The ANOVA revealed a sig. Validity effect (i.e., latency advantage
for visual targets ipsilateral vs. contralateral to the auditory cue), F=64.10,
p<.001, and a sig. Validity x Condition interaction, F=17.37, p<.001; post
hoc contrasts revealed a greater Validity effect in the 80% TAC condition.
The only sig. interaction involving Group was Group x Validity, F=6.263,
p=.02, indicating a larger Validity effect for SZ vs. controls.
Conclusion: In both non-disordered individuals and patients with SZ,
visual attention is reflexively drawn to the spatial location of an auditory
stimulus, even if the target visual event is unlikely to occur at that location. The magnitude of this effect is larger in SZ, however, suggesting
that, on incongruent trials, individuals with SZ are relatively slower to disengage attention from an auditory signal.
References: Maruff, P., Danckert, J., Pantelis, C., & Currie, J. (1998).
Saccadic and attentional abnormalities in patients with schizophrenia.
Psychological Medicine, 28, 1091-1100. Posner, M. I. (1980). Orienting of
attention. Quarterly Journal of Experimental Psychology, 32, 3-25.
P-05
Psychotic Disorders II
P-05-01
Demographic, social and clinical correlates in outpatients
with schizophrenia: A comparison with affective disorders
Amanda Wheeler
Waitemata DHB, CRRC, Waitakere, New Zealand
Introduction: The objective of this study was to describe the demographic and social characteristics and service utilisation of people with
schizophrenia and to compare this with (a) people with affective disorders
in four public psychiatric services in New Zealand and (b) the New Zealand
general population; and to examine conformity with evidence-based
pharmacological treatment of schizophrenia.
Method: All adult community files were reviewed in October 2004
(n=6165). Patient characteristics, social and functional indicators, diagnosis,
duration of illness, and admission information were recorded and
analysed. Antipsychotic treatment was recorded for those with schizophrenia.
Results: Outpatients with schizophrenia made up 47% of the sample;
66% male, mean age 39 years and mean illness duration 14 years. Sixtyseven percent of schizophrenia outpatients had never been married, 69%
had no meaningful activity, 49% had no formal qualifications, 24% were
living in group homes and 26% were treated compulsorily. These social
and service use characteristics were consistently different compared to
outpatients with affective disorders and the general population; schizophrenia patients were the most impaired, depression the least and the
bipolar group in between. The majority of schizophrenia patients received
evidence-based antipsychotic treatment; 84% received monotherapy;
81% prescribed an atypical; 33% prescribed clozapine.
Conclusion: The study shows significant clinical and social disability for
schizophrenia patients in areas of work, qualifications, relationships, living situation and specialist mental health service use exist despite evidence-based pharmacological treatment. To improve outcomes optimal
care must incorporate existing evidence-based, cost-effective interventions that focus on both symptoms and function. More effective treatments also need to be developed.
139
P-05-02
Metabolic syndrome in schizophrenia? a study from India
Ravindra Rao
AIIMS, Psychiatry, New Delhi, India
Meera Vaswani
Introduction: The reported rate of metabolic syndrome in patients of
schizophrenia is highly variable across different studies. Additionally, there
are no published studies on metabolic syndrome in patients of schizophrenia from India. The current study aimed to determine the prevalence
of metabolic syndrome in patients of schizophrenia as well as its association with various factors.
Method: A cross sectional study was conducted in the psychiatry outpatient facility of a tertiary care hospital, on a sample (chosen as per convenience) of patients suffering from schizophrenia (diagnosed according
to the International Classification of Disease, version 10). The sociodemographic and clinical details were collected. As components of the metabolic syndrome, the waist circumference, blood pressure, fasting blood
sugar and lipid profiles (serum triglyceride and High Density Lipoprotein)
were assessed. Metabolic syndrome was defined using the criteria proposed by the International Diabetes Federation Consensus group. The
mean and standard deviation for continuous variables, and the frequency
for categorical variables were computed. The metabolic and the non
metabolic syndrome group were compared using chi-square test. Finally
logistic regression was performed.
Results: 76 patients were included in the study. The mean age was 31.89
years (SD: 10.5), and the mean illness duration was 5.6 years (SD: 4.8).
62% were males; 80% were on antipsychotics and 26.3% had family history of cardiovascular disease. 84% had at least one component and
26.4% had three or more components of the metabolic syndrome above
the cut off value. Waist circumference and serum HDL was significantly
above the cut off value in females (p = 0.03 and 0.004 respectively).
Metabolic syndrome was present in 22.37% of the sample. The prevalence of metabolic syndrome increased with increasing age. Illness duration of more than 10 years was significantly associated with the occurrence of metabolic syndrome. On applying logistic regression, none of the
variables was significantly associated with metabolic syndrome.
Conclusion: This study highlights the prevalence of metabolic syndrome
in patients of schizophrenia in Indian setting. The clinicians treating such
patients need to be sensitized on the presence of metabolic syndrome.
P-05-03
Th1, Th2 and Th3 immune reactivity in patients with first
episode psychosis
Bojana Avgustin
University Psyhiatric Hospital, Ljubljana, Slovenia
Brigita Novak Sarotar, Rok Tavcar
Introduction: Alterations of cytokine levels represent the most consistent
finding in the studies on the involvement of the immune system in the
etiology of schizophrenia. In order to determine Th1, Th2 and Th3
immune reactivity in early stages of psychosis, the in vitro secretion of IFNgamma, IL-4 and IL-10 by peripheral blood mononuclear cells (PBMC)
after stimulation with mitogens between patients with first episode psychosis, acute exacerbation of psychosis, patients with chronic schizophrenia and healthy controls was compared.
Method: 17 patients with first episode psychosis, 19 patients with acute
exacerbation of schizophrenia, 18 patients with chronic schizophrenia
and 17 matched healthy subjects from the same population without psychiatric history were included in the study. All patients included in the
study had been receiving antipsychotic medications. PBMC cultures were
incubated with polyclonal activators, the concentration of cytokines was
measured using ELISA kits.
Results: In vitro IL-4 and IL-10 cytokine secretion in patients with first
episode psychosis, was significantly increased compared to healthy controls. No significant differences in IL-4 and IL-10 cytokine secretion were
observed between the patients subgroups. No significant differences
were observed in the in vitro IFN-gamma secretion between the patients
subgroups compared to healthy controls.
Conclusion: Our findings indicate a significant increase of in vitro reactivity of Th2 and Th3 arm of cell mediated immunity in patients with first
140
episode psychosis compared to healthy controls. The significance of

immune alterations in schizophrenia is not clear at the moment. The
immune activation might in combination with genetic and/or other modulating factors be an important underlying pathogenetic mechanism of
the schizophrenia. The immune abnormalities could also be the by product
of the complex physiological changes in schizophrenia.
References: Cazzullo CL, Sacchetti E, Galluzzo A, Panariello A, Colombo
F, Zagliani A et al. Cytokine profiles in drug-naive schizophrenic patients.
Schizophr Res. 2001;47:293-8. Kim YK, Myint AM, Lee BH, Han CS, Kim
DJ, Leonard BE. Th1, Th2 and Th3 cytokine alteration in schizophrenia.
Th1, Th2 and Th3 cytokine alteration in schizophrenia. Prog
Psychophamacology Biological psychiatry. 2004; 28:1129-34.
Pollmacher T, Haack M, Schuld A, Kraus T, Hinze-Selch D. Effects of
antipsychotic drugs on cytokine networks. J Psychiatr Res. 2000;34:36982.
P-05-04
An international, multisite, epidemiological study of suicidality and psychosis in bipolar school-age children
USA
Roberto Yunez, Sandra Lopez, Sandra Castilla-Puentes, Wilma CastillaPuentes, Maria Teresa Alvarado, Carlos Sanchez-Russi
Introduction: To compare thoughts about death, wishing to be dead,
thoughts of suicide, suicide plans, hallucinations and delusions in three
children community samples with and without bipolar disorder (BPD).
Method: A total of 614 children, 8-18 y.o. (female, 52.0%; male, 48.0%;
mean age 12 years, SD=3), from a stratified random sample of schools in
countries, including Colombia (N=293), Argentina (N=106), and Mexico
(N=215) were interviewed using the School Age Schedule for
Schizophrenia and Affective Disorders (K-SADS).
Results: BPD children were significantly more likely than non-BP to have
higher rates of psychosis (70 vs 1%; 95% CI= 36,103, P<0.0001) and suicidality (60 vs. 1%; 95% CI=23,94., P<0.0001). Depressive symptoms
were found in 90% of BPD patients, with mixed/cycling episodes associated with more severe depressive symptomatology. Increased energy and
elated mood differentiated patients diagnosed with BPD. Rates of bipolarity, suicidality, and psychosis were similar in the three sites.
Conclusion: Children with BPD usually have significant suicidality and
psychotic symptoms. Need prompt identification and treatment of BPD
because at least in adults, the highest rate of suicide happens during the
first years of illness.
References: Haugaard JJ. Recognizing and treating uncommon behavioral and emotional disorders in children and adolescents who have been
severely maltreated: bipolar disorders.Child Maltreat. 2004 May;9(2):131-8.
Shaffer D. The epidemiology of teen suicide: an examination of risk factors. J Clin Psychiatry. 1988;9 Suppl:36-41.
P-05-05
No associations between schizophrenia and D22S280
marker on synapsin III gene in Korean males
Yu-Sang Lee
Yongin Mental Hospital, Psychiatry, Republic of Korea
Chong-Won Park, Suk-Jin Lee, Seung-Yeoun Lee, Kyung Sue Hong
Introduction: Synapsin III near VCFS region on 22q, of which role is
affecting synaptic vesicle formation and neurodevelopment. It could be
an interesting candidate gene for schizophrenia. D22S280 is a highly
polymorphic genetic marker residing in synapsin III. We examined association of D22S280 marker on synapsin III with Korean patients with schizophrenia.
Method: The subjects were 46 male Korean patients with schizophrenia
and 60 male normal controls. Using polymerase chain reaction, gel electrophoresis, ABI 310 genetic analyzer, and GeneScan Collection 3.1 software, we confirmed genotypes of D22S280 marker. We examined HardyWeinberg equilibrium and case-control association using SAS/Genetic 9.1.3.
Results: Genotypes of both schizophrenia and control groups were in
Hardy-Weinberg equilibrium. We could not find any significant statistical
differences in allele-wise (2=10.4, df=6, p=0.098) and genotype-wise

(2=22.1 df=19, p=0.258) analyses of D22S280 marker between schizophrenia and normal controls. Individual allele analyses with df=1 showed
significant differences in A1 (p=0.025) and A7 (p=0.034) allele, which
were not significant following Bonferroni corrections (A1: p=0.177, A7:
p=0.235).
Conclusion: We couldnt find any association between schizophrenia
and synapsin III gene. Considering the limitation of small number of subjects, further investigations are needed.
References: Kao HT, Porton B, Czernik AJ, Feng J, Yiu G, Haring M,
Benfenati F, Greengard P: A third member of the synapsin gene family,
Proc Natl Acad Sci U S A 1998, 95:4667-4672
P-05-06
The differences of EEG coherence between schizophrenia
and bipolar disorder
was used to collect baseline information on demographics, medical and

psychiatric history, and concomitant medication use. Data were selfreported by patients or reported by enrolling physicians. Descriptive baseline data on 18,094 patients with schizophrenia are presented here.
Results: Patients (mean age, 41.6 years; 55.1% male; 60.0% white)
came primarily from the United States or Brazil (73.0%). 17.6% of
patients had hypertension, 14.8% had hyperlipidemia, 46.5% currently
smoked, 28.9% had a body mass index of = 30 kg/m2, and 7.7% had
diabetes at baseline; all of these characteristics are major cardiovascular
risk factors. Mean time since schizophrenia diagnosis was 10.4 years, and
average Clinical Impression Score was 5.2 (range, 1-8). At baseline, 71%
of patients were using antipsychotic drugs. Although almost 80% of
patients were using concomitant medications, less than 3% were using
antihypertensive drugs or statins.
Conclusion: The ZODIAC baseline data suggest that this study population has a substantial prevalence of cardiovascular risk factors and that
hyperlipidemia and hypertension may be undertreated.
Yu-Sang Lee
Yongin Mental Hospital, Psychiatry, Republic of Korea
Yong-Kyu Kim, Chong-Won Park, Hong-Seok Oh, Kyung Sue Hong,
Seung-Yeoun Lee
P-05-08
Development of a reliable method for parcellation of the
frontal pole
Introduction: EEG coherence could imply the connectivity between two

different areas of the brain, which is known to be important in the pathophysiology of bipolar I disorder (BPD I) and schizophrenia. The authors
investigated EEG coherence in patients with BPD I and schizophrenia to
examine the connectivity of neural circuit.
Method: EEGs were recorded in 15 schizophrenia and 14 bipolar disorder patients, and 14 age-matched normal control subjects from 16 electrodes with linked-ear reference. Spectral parameters and coherence were
calculated for the alpha bandwidth (8~13Hz) by a multi-channel autoregressive model using 20 artifact-free 2-seconds epochs and the differences were compared among three groups by two different statistical
methods; F-test and Kruskal-Wallis test. Furthermore, when there were
significant differences among three groups, Scheffes multiple comparison
tests were provided and Jonckheere-Terpstra tests for the ordered alternative were given.
Results: In the intra-hemispheric comparison, left frontal coherence was
increased in order of control, BPD I and schizophrenia. In the inter-hemispheric comparison, (1) inter-prefrontal coherence in BPD I was significantly
higher than normal controls, and (2) inter-prefrontal coherence in schizophrenia was significantly lower than control.
Conclusion: These results suggest that (1) both schizophrenia and BPD I
were diseases having the abnormality of neural circuit connectivity in both
frontal and prefrontal lobe, and (2) the abnormality was more severe in
schizophrenia than in BPD I. Furthermore, the data support that common
pathogenetic process may reside in both schizophrenia and BPD I.
References: 1. Winterer G, Coppola R, Egan MF, Goldberg TE, Weinberger DR. Functional and effective frontotemporal connectivity and
genetic risk for schizophrenia. Biol Psychiatry 2033: 54: 1181-92 2. Moller
HJ. Bipolar disorder and schizophrenia: distinct illnesses or a continuum?
J Clin Psychiatry. 2003;64 Suppl 6:23-7
P-05-07
Cardiac risk factors and schizophrenia: An analysis of
18,094 patients enrolled in an international comparative
trial of olanzapine and ziprasidone
Brian Strom
University of Pennsylvania, Center for Clinical Epidemiology,
Philadelphia, USA
Gerald Faich, Sybil Eng, Robert Reynolds, Fred Rappard, John Kane
Introduction: Ziprasidone has modest QTc-prolonging effects, but it is
not known whether this translates into an increased risk of cardiovascular
events. To address this issue, a large, international, open-label, randomized, post-marketing study, the Ziprasidone Observational Study of
Cardiac Outcomes (ZODIAC), has been conducted to compare the cardiovascular safety of ziprasidone and olanzapine.
Method: Between February 2002 and February 2006, over 18,000
patients with schizophrenia from 18 countries were enrolled from a variety of psychiatry practice settings. A physician-administered questionnaire
John P. John
NIMHANS, Psychiatry, Bangalore, India
B. S. Yashavantha, D. J. Ramesh, Lei Wang, Mokhtar Gado, S
Ravishankar, Sanjeev Jain
Introduction: Precise delineation of the FP(BA 10) from the posterior
structures of the prefrontal cortex (PFC) has not been achieved on MR
images due to lack of a natural sulcal demarcation that separates these
areas. Hence, a landmark-based definition of the posterior boundary of
the FP is of paramount importance to study this important frontal subregion in various neuropsychiatric conditions. In our recent MRI-based
parcellation study of the PFC, we have suggested that the coronal plane
containing the anterior termination of the olfactory sulcus (ATOS) could
be employed as a landmark for designating the posterior boundary of the
FP (John et al., 2006, in press). We report the inter-rater reliability of estimating the FP gray matter volumes utilizing the above landmark-based
definition of the FP.
Method: Using high resolution MPRAGE MR scans, independent raters
produced two sets of manual segmentations of the FP of both hemispheres in five subjects. Manual outlining of FP was carried out on successive coronal sections starting from the section anterior to that containing
the ATOS, which was defined as the posterior boundary of the FP. Image
pre-processing and manual segmentation were carried out using Analyze
7.0 (Robb et al., 1989). The inter-rater reliability of gray matter volumes
generated by manual segmentation of the FP by the two independent
raters was estimated by calculating the intra-class R coefficient (ICC).
Results: FP gray matter volumes obtained using the above method by the
two independent raters yielded an average right FP gray matter volume
4770.50 mm3 and left FP gray matter volume of 5586.50 mm3. The ICC
of the FP gray matter volume estimates between the two raters was 0.91.
Conclusion: The high inter-rater reliability (ICC = 0.91) of gray matter
volumes generated using this method supports its potential utility in conducting non-biased comparisons of groups of subjects with and without
neuropsychiatric disorders.
References: 1.John, J. P., Wang, L., Moffit, A.J., Singh, H. K., Gado, M.
H., Csernansky, J. G.(2006) Inter-rater reliability of manual segmentation
of the superior, inferior and middle frontal gyri. Psy Res Neuroimaging (in
press) 2.Robb, R.A., Hanson, D.P., Karwoski, RA., Larson, A.G., Workman,
E.L., Stacy, M.C.,(1989). Analyze: a comprehensive, operator-interactive
software package for multidimensional medical image display and analysis. Comput. Med. Imaging Graph. 136, 433-454.
P-05-09
Association study of olanzapine-induced weight gain and
treatment response with 5-HT2C gene polymorphism in
female schizophrenic patients
Martina Rojnic Kuzman
Zagreb University Hospital , D. of Psychiatry, Croatia
Vesna Medved, Nada Bozina, Nikolina Jovanovic, Ljubomir Hotujac
141
Introduction: Several reports showed functional -759C/T polymorphism,

especially T allelic variants to be associated with lower weight gain during
atypical antipsychotics treatment, although the results are far from being
consistent. Most of these studies found associations only among male
subjects, but not among female patients. Since 5HT2C is situated on X
chromosome, we could expect differences in results of association studies
in males vs. female subjects. A few reports showed -759C/T polymorphism to be associated with treatment response in schizophrenic subjects.
We investigated the relationships between functional genetic variants of
5-HT2C and olanzapine-induced weight gain and treatment response to
olanzapine in female schizophrenic patients.
Method: We recruited 116 female schizophrenic patients treated with
olanzapine for up to 4 months. Treatment response, using Positive and
Negative Syndrom Scale (PANSS) and body mass index (BMI) were
assessed and relationships with -759C/T 5HT2C allelic variants were studied.
Results: No significant associations were found between treatment
response, measured with changed Total PANSS and all PANSS subscales
and BMI increase with 5HT2C variants. For analysis of -759C/T allelic variants of 5-HT2C gene PCR-RFLP method was applied according to previously described procedure
Conclusion: Our data do not support the role of 759C/T 5HT2C in olanzapine-induced weight gain and treatment response in female shizophrenic patients.
References: Pooley EC, Fairburn CG, Cooper Z, Monsheel SS, Cowen PJ,
Harrison PJ. A 5HT2C receptor promoter polymorphism (HTR2C-759C/T)
is associated with obesity in women, and with resistance to weight loss in
heterozygotes. Am J Med Genet 2004;126B:124-127 Yuan X, Yamada K,
Ishiyama-Shigemoto S, Koyama W, Nonaka K. Identification of polymorphic loci in the promoter region of the serotonin 5HT2C receptor gene
and their association with obesity and type II diabetes. Diabetologia 2000;
43: 373-376 Reynolds GP, Zhang ZJ, Zhang XB. Association of antipsychotic weigt gain with a 5-HT2C polymorphism. Lancet 2002; 359: 20862087 Templeman LA, Reynolds GP, Arranz B, San L. Polymorphisms of the
5HT2C receptor and leptin genes are associated with antipsychotic druginduced weight gain in Caucasian subjects with a first-episode psychosis.
Pharmacogenetics and Genomics 2005; 15: 195-200 Basile VS, Masellis
M, DeLuca V, Meltzer HY, Kennedy JL. 759C/T genetic variation of the
5HT2C receptor and clozapine-induced weight. Lancet 2002; 360: 17901791
P-05-10
Transcription factors of the nurs and retinoid X receptor
subgroups are crucial factors for dopamine-related neuroadaptation: Implication for antipsychotic drug effects
Daniel Levesque
University of Montreal, Faculty of Pharmacy, Canada
Claude Rouillard, Emmanuelle Bourhis, Jerome Maheux, Cecile Vue,
Celine Hodler
Introduction: Dopaminergic systems in the brain adapt in response to a
variety of stimuli from the internal and external world. The antipsychotic
drug treatment represents one of such external stimuli that alter
dopamine neurotransmission for which the molecular and cellular mechanisms underlying antipsychotic drug responses are still incompletely
understood. In recent years, evidence has emerged that certain types of
transcription factor of the nuclear receptor family, specifically Nur77 and
retinoid X receptors, play an important role in the adaptation, and importantly, in the homeostatic regulation of dopaminergic systems.
Method: We compared various behavioral and biochemical parameters
between Nur77 knockout (-/-) and wilt type (+/+) mice in basal and
antipsychotic-challenged conditions. In addition, we tested the effect of
various retinoid ligands on dopamine-mediated activities.
Results: Nur77 (-/-) mice display numerous behavioral alterations associated with dopamine functions in the central nervous system. We report
that Nur77 deficient mice display enhanced spontaneous locomotor
activity, greater sensitivity to a small dose of the dopamine D2 receptor
agonist quinpirole acting mainly at autoreceptor sites and higher levels of
the dopamine metabolite DOPAC compared to wild type mice. Dopamine
turnover disturbances are also found following acute challenge with
haloperidol. These alterations are associated with increased tyrosine
hydroxylase expression and activity and reduced catechol-O-methyltransferase expression. Nur77 (-/-) mice also display altered cataleptic and oro-
142
facial dyskinetic responses following antipsychotic drug treatment.

Interestingly, retinoid ligands can modulate antipsychotic drugs as well as
amphethamine-induced locomotor responses in wild type, but not in
Nur77 (-/-) mice.
Conclusion: These results indicate that Nur77 and retinoids are involved
in neuroadaptive responses following antipsychotic drug treatment.
These findings call for a reassessment of our fundamental understanding
of the molecular and cellular basis of dopaminergic transmission. Given
that diseases such as schizophrenia are thought to involve maladaptation
of dopamine signalling, these findings might lead to new insight into this
pathology and offer new avenues for drug development.
References: Levesque D and Rouillard C, Nur77 and retinoid X receptors:
crucial factors in dopamine-related neuroadaptation, Trends Neurosci. in
press, 2007.
P-05-11
Adaptive immunity to diphtheria in patients with schizophrenia
Tamara Vetlugina
Mental Health Institute, Psychoneuroimmunology Laborato, Tomsk,
Russia
Timur Turyanov, Olga Lobacheva, Renat Valinurov
Introduction: To study immune response of schizophrenic patients to
injection of preparations comprising diphtheritic anatoxin.
Method: Antitoxic antibody titer to diphtheria was identified in passive
hemagglutination reaction with erythrocytic diphtheritic diagnosticum.
Antibody titer 0 - 1:40 was taken as low, 1:80-1:160 - middle; 1:320 and
higher - high. As protective antibody titer not less than 1:40 is regarded,
antibody titer 0 - 1:20 - lower than protective.
Results: 280 schizophrenic inpatients were examined with disease duration not less than 5 years; and 213 persons - staff of hospital (group of
comparison). According to epidemic indications all examined were administered full course of vaccination with associative preparations containing
diphtheritic anatoxin. Identification of titer of diphtheritic anatoxin in
blood serum of examined persons was conducted twice: before vaccination (initial titer) and a month after ending course of vaccination (postvaccinated titer). It has been established that initial level of antitoxic antibodies to diphtheria was lower in group of schizophrenic patients as compared with group of comparison with high degree of reliability
(p < 0,001). Both in group of comparison and in group of schizophrenic
patients accumulation of persons with initial antibody titer to diphtheria
lower than protective (0 - 1:20) occurs. In group of comparison, percent
of such persons has constituted 31,7%, in general group of patients 44,1%, and in group of patients with adverse variant of course of schizophrenia (continuous type of course, duration of disease more than
15 years, long term of intake of neuroleptics) 55,6% of patients before
conducting course of vaccination had not a protective antibody titer to
diphtheria. Serological investigations, conducted month after course of
vaccination (logarithmic phase of antibody formation), have established a
high level of adaptive immune response to diphtheria both in patients and
in group of comparison. Low and middle post-vaccinated titers of antibodies in group of patients and in group of comparison were in 10,8 and
9,5% of examined, respectively. High post-vaccinated titers of specific
antitoxic antibodies to diphtheria were in 89,2% of patients and 90,5%
of persons from group of comparison.
Conclusion: Thus, schizophrenic patients are characterized by high
immune reactivity to diphtheria in logarithmic phase of antibody formation and quicker (as compared with mentally healthy persons) reduction
antibody decrease and accumulation of persons with antitoxic antibody
titer to diphtheria lower than protective one.
P-05-12
Asenapine displays distinctive induction patterns of c-fos
mrna expression in rat forebrain regions
Barbara E. H. Sumner
Organon Laboratories Ltd, Dpt of Molecular Biology, Lanarkshire, United
Kingdom
Mohammed Shahid, Erik H. F. Wong, Brian Henry
Introduction: Asenapine is a novel psychopharmacologic agent under
development for the treatment of schizophrenia and bipolar disorder. We
mapped the neuroanatomic sites of response to asenapine in the male rat
forebrain, using changes in c-fos mRNA expression as a marker for cell
activation.
Method: After daily handling for 5 days to ensure low basal c-fos mRNA
expression, 24 male rats received asenapine 0.05, 0.1, or 0.5 mg/kg subcutaneously or vehicle. Animals were sacrificed and brains removed and
processed for c fos in situ hybridization histochemistry. Autoradiographic
results were quantified in 43 brain regions and subregions. Results in each
region are expressed as percentage increase in cell activation with asenapine versus vehicle.
Results: Asenapine effects varied with dose and brain region. At 0.05
mg/kg, asenapine significantly increased c-fos response in the dorsolateral,
dorsomedial, ventrolateral, and ventromedial quadrants of the striatum
(75%-131% anteriorly; up to 88% posteriorly) and preferentially in the
nucleus accumbens shell (82%). At 0.1 mg/kg, activation reached 241%
in the striatum anteriorly and 146% in the nucleus accumbens shell, with
13 additional areas activated: the medial prefrontal, retrosplenial, and
parietal cortices (35%, 21%, 21%, respectively); lateral septum (43%);
olfactory tubercle (21%); hippocampal CA1 and CA2 cell fields (40%,
28%); lateral (both subregions) and medial habenula (22%-36%); and
the dorsal, medial, and ventral thalamus (15%, 30%, 19%).
At 0.5 mg/kg, the retrosplenial and parietal cortices, hippocampal cell
fields, and habenular and thalamic regions were no longer responsive.
However, significant activation was noted in the nucleus accumbens core
(32%), hypothalamic and thalamic paraventricular nuclei (93%, 38%),
and medial amygdaloid nucleus (79%).
Conclusion: Asenapine produces different patterns of neuronal activation depending on dose. The pattern of activation suggests that asenapine may influence activity in extended neuronal circuitry believed to be
relevant to the pathology of schizophrenia, including cognition, stress,
and emotional state.
P-05-13
Grey matter correlates of skin conductance levels in
patients with schizophrenia and healthy volunteers:
A voxel-based morphometry study
Antonio Zuardi
University of Sao Paulo, Psychiatry - Ribeira, Ribeirao Preto, Brazil
Thiago Borduqui, Jaime Hallak, Jose Alexandre Crippa, Davi Araujo,
Antonio Carlos Santos
Introduction: Electrodermal activity has been considered as a potential
source to identify subgroups of schizophrenics. However, the neural
mechanisms that are the base of the electrodermal responsiveness in
schizophrenia are not well-known. Thus, the aim of the present study was
to determine if schizophrenic patients with different skin conductance
levels (SCL) show differences in grey matter (GM) volume estimated
through magnetic resonance imaging (MRI).
Method: Thirty-four schizophrenic patients and a corresponding number
of healthy volunteers, matched according to sex, age, handedness, socioeconomic status and years of education, were selected. All the patients
were using anti-psychotics and had their diagnoses confirmed by the
Structured Clinical Interview for DSM-IV Axis I Disorders Clinician
Version. The patients were submitted to the experimental session only
when their score in the BPRS was lower then present in mild degree in
all the scale items, except for negative symptoms. The electrodermal
activity was measured during five minutes at rest and in comfortable conditions. The SCL mean of the control group less two standard deviations
was used as a cut-off value to identify those schizophrenic patients with
low SCL. Three groups were obtained, according to the electrodermal
level: control, schizophrenic with normal SCL and schizophrenic with low
SCL. MRI was performed with a Siemens Magneton 1.5 T imaging system. The optimized voxel-based morphometry protocol was implemented
within MATLAB 7.0 (Mathworks Inc.) through Statistical Parametric
Mapping 2.
Results: Compared to controls, schizophrenic patients presented abnormalities in regional GM volume in superior and medial frontal lobes, paracentral lobule, cingulated, transverse temporal, insula, precuneus and
occipital lobe. When comparing the two groups of schizophrenia, it was
observed that the low SCL group presented smaller regional GM density
in the right superior frontal lobe and in the right anterior cingulated.
Conclusion: Accordingly, these results suggest that these brain areas may
be involved in the modulation of the SCL in schizophrenia and could be
altered in a subgroup of patients. Further studies may possibly identify
cognitive and emotional characteristics particular to this subgroup of
schizophrenic patients.
P-05-14
A study of gastro-intestine side effect of clozaril in the
treatment of schizophrenic disorders
Cheng-Chung Chen
Kaohsiung Medical University, Psychiatry, Ming, Kaohsiung City, Taiwan
Wen-Ya Chour, Shu-Fang Shou, Chia-Hua Taso, Chiao-Li Ke
Introduction: Clozaril is famous for it Once clozapine, always clozapine, and also being classified as prescriptions in the last line or treatment
resistance case. This is a retrospective comparative study regarding the
adjunctive therapy using G-I drugs for helping defecation in the treatment
of patients with or without clozaril. The major goal is to explore the possible side effect of clozaril in costipation as a preliminary report for further
clinical use.
Method: This is a cross sectional analysis of an psychiatric hospital cases.
The study group was comprised of patients under the diagnosis of schizophrenic disorders using clozaril as major neuroleptics (N=153). The control group was comprised of patients using neuroleptic other than clozaril
(N=304). The controlled factors include sex and duration of illness.
Statistical methods include Chi-square, t-test and the significant difference is setting p-value at .05.
Results: A total of cases were included in this analysis. The clozaril group
include 70 males and 83 females with a mean age of 40.8 years old. The
controlled group include 158 males and 163 females with a mean age of
41.2 years old. There was no statistically significant difference in the sex
and the combinations of anticholinergics in these two groups. The clozaril
group used more softants (magnesium oxide), stool passenger (sennosides A+B), and laxatics (bisacodyl).
Conclusion: The results show that the second dangeous side effect of
paralytic ileus induced by clozaril should be carefully monitored by daily
oral intake, type of food and balance of water intake (avoid compulsive
water drinking). Also indicated that starting clozaril should monitor the
combination of G-I drugs and daily passage in practice.
References: 1. Flanagan, R.J., et al., Suspected clozapine poisoning in
the UK/Eire, 1992-2003. Forensic Sci Int, 2005. 155(2-3): p. 91-9. 2.
Lieberman, J.A., et al., Effectiveness of antipsychotic drugs in patients
with chronic schizophrenia. N Engl J Med, 2005. 353(12): p. 1209-23.
P-13
Psychotic Disorders III
P-13-01
Asenapine: Effect on a subchronic phencyclidine-induced
reversal learning deficit in rats
Jo C. Neill
University of Bradford, School of Pharmacy, United Kingdom
Naji F. Idris, Hugh Marston, Mohammed Shahid, Erik H. F. Wong
Introduction: Asenapine is a novel psychopharmacologic agent being
developed for the treatment of schizophrenia and bipolar disorder.
Phencyclidine (PCP) can induce cognitive deficits in animal models similar
143
to deficits seen in schizophrenia. We assessed the effects of acute and

chronic treatment with asenapine and atypical antipsychotics on a PCPinduced reversal learning deficit in the rat.
Method: Female hooded Lister rats were trained to press an active lever
for a food reward. Rats achieving 90% criterion on 3 consecutive days
were trained to reverse this behavior and were then treated with PCP
2 mg/kg intraperitoneally (IP) twice daily for 7 days, followed by 7 days
drug free. For the acute treatment study, rats received a single dose of
asenapine (0.025-0.1 mg/kg), risperidone (0.05-0.2 mg/kg), olanzapine
(0.5-1.5 mg/kg), or vehicle (n=8-10/group). For the chronic treatment
study, rats received asenapine 0.075 mg/kg subcutaneously twice daily,
risperidone 0.2 mg/kg IP once daily, olanzapine 1.5 mg/kg IP once daily,
or vehicle for 28 days. Data from serial testing were analyzed by ANOVA
and Dunnetts t test.
Results: Subchronic PCP administration induced a significant selective
reversal learning deficit that was maintained over the course of the study.
With acute treatment, the reversal learning deficit was significantly
attenuated by asenapine 0.05 and 0.075 mg/kg, risperidone 0.2 mg/kg,
and olanzapine 1.5 mg/kg (P<0.05 to P<0.001). With chronic treatment,
asenapine significantly decreased the reversal learning deficit on days 3,
7, and 17 (P<0.01, P<0.05, and P<0.05, respectively). Risperidone effects
were significant on days 3, 7, and 28 (P<0.01, P<0.05, and P<0.05).
Olanzapine effects were significant on days 3 and 17 (both P<0.05).
Conclusion: Given acutely, asenapine attenuated the PCP-induced cognitive deficit in a dose-related manner. Given on a chronic basis, the
effects of asenapine were maintained over time. Asenapine results were
similar to those with risperidone and olanzapine. The improvement in
cognitive function seen in this model suggests potential benefit with asenapine in the treatment of schizophrenia.
P-13-02
Asenapine has cognitive function effects in acute schizophrenia: A placebo- and risperidone-controlled trial
Steven G. Potkin
University of California, Irvi, Clinical Research, Orange, USA
Kirstin Fleming, Brendon Binneman, David Keller, Larry Alphs, John
Panagides
Introduction: Asenapine is a novel psychopharmacologic agent under
development for the treatment of schizophrenia and bipolar disorder.
From a previously reported 6-week double-blind study of asenapine in
patients with acute schizophrenia, we report the results of cognitive
assessments.
Method: Patients were treated with asenapine 5 mg twice daily (n=59),
risperidone 3 mg twice daily (n=59), or placebo (n=62); a double-dummy
technique was used to maintain blinding. A comprehensive cognitive test
battery was administered after the morning dose at baseline, week 3, and
week 6 or last visit; last observations were carried forward for patients not
completing the trial. The following domains were tested: speed of processing (Category Fluency, Verbal Fluency, Trails A and B, Digit Symbol
Substitution Test [DSST]), working memory (Letter-Number Span Test),
verbal learning and memory (Rey Auditory Verbal Learning Test, which
includes immediate and delayed recall and delayed recognition), visual
learning and memory (Benton Visual Retention Test), and reasoning and
problem solving (Wisconsin Card Sorting Test [WCST]). Placebo-corrected
effect sizes (Dunlaps D) were calculated for individual neurocognitive
tests to evaluate the impact of asenapine on neurocognitive functioning
in schizophrenia.
Results: Asenapine-treated patients showed improvements on tests of
verbal learning and memory (Dunlaps D 0.45, 0.38, and 0.25 for immediate and delayed recall and delayed recognition, respectively) and speed
of processing (0.43, 0.34, and 0.31 for Trails A time, DSST, and Verbal
Fluency, respectively). Risperidone-treated patients showed improvements
in speed of processing (0.31 and 0.24 for Trails A time and DSST, respectively), but performance worsened in reasoning and problem solving
(-0.35 and -0.31 for WCST percentage of perseverative errors and total
number correct, respectively).
Conclusion: Patients treated with asenapine showed improvements in
domains of cognitive function that are particularly relevant to functional
outcome in schizophrenia.
144
P-13-03
Asenapine shows high affinity and potent antagonist
activity at an ensemble of human serotonin receptor
subtypes
Mohammed Shahid
Organon Laboratories Ltd, Lanarkshire, United Kingdom
Erik H. F. Wong
Introduction: Antipsychotic drugs show different binding profiles to
serotonin receptor subtypes, which may affect their efficacy and tolerability
in schizophrenia treatment. In this study, we compared asenapine (a novel
psychopharmacologic agent under development for the treatment of
schizophrenia and bipolar disorder) and the atypical antipsychotics olanzapine and risperidone in terms of binding affinity and functional effects
at cloned human serotonin receptors (5 HT1A/1B, 5-HT2A/2C, 5-HT6,
and 5-HT7).
Method: Membranes and whole cells from cell lines expressing cloned
human serotonin receptors were used to assess receptor binding and
functional activity, respectively. Functional activity was assessed through
changes in intracellular cAMP (5-HT6, 5-HT7) or Ca2+ (5-HT1A, 5-HT1B,
5-HT2A, 5-HT2C) levels, induced at submaximal agonist concentration.
Results: Asenapine bound to 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2C, 5-HT6,
and 5-HT7 receptors with higher affinity (pKi 8.6, 8.4, 10.2, 10.5, 9.6,
9.9) than olanzapine (pKi 5.8, 6.6, 8.9, 8.4, 8.5, 7.4) or risperidone (pKi
6.8, 7.3, 9.7, 8.2, 5.7, 9.1). Asenapine showed no agonist activity at any
of these receptors under the assay conditions used. Asenapine acted as
an antagonist at 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2C, 5-HT6, and 5-HT7
receptors (pKB 7.4, 8.1, 9.1, 9.0, 8.0, 8.5) with generally greater potency
than olanzapine (pKB <5.5, 6.7, 8.6, 7.7, 7.4, 6.9) or risperidone (pKB
6.4, 7.7, 9.2, 6.6, <5, 8.5). In addition, asenapine bound with similar
affinity and with comparably potent antagonist effects at 5 HT6 and 5HT7 receptors, whereas olanzapine and risperidone showed more disparate results for binding affinity and for antagonist activity at these 2
receptors.
Conclusion: In this study, asenapine displayed a unique human receptor
signature, with greater binding affinity and more potent and distinct
antagonist activity than olanzapine and risperidone at a number of serotonin receptor subtypes. The pattern of binding and modulating effects
seen with asenapine at these serotonin receptors may contribute to favorable efficacy and tolerability profiles in patients with schizophrenia or
bipolar disorder.
P-13-04
Effects of selegiline on negative symptoms of schizofrenia;
a double-blind placebo controlled study
Ebrahim Abdollahian
Mashhad Univ. of Med. Sciences, Psychiatry, Iran
S. Kaveh Hodjat
Introduction: Introduction: It has been suggested that schizophrenic
negative symptoms may be manifestations of regionally deficient CNS
dopaminergic activity. We sought to test this hypothesis by openly treating patients on chronic antipsychotic medication who showed prominent
negative symptoms with low-dose selegiline (5 mg b.i.d.), a monoamine
oxidase-B inhibitor that selectively enhances dopaminergic activity.
Method: Methods: Eighty patients meeting DSM-IV-TR criteria for chronic
schizophrenia with prominent negative symptoms (Positive And Negative
Symptoms of Schizophrenia-Negative (PANSS-N) subtype>15) were studied. Subjects had been kept at their current antipsychotic medication
dose levels for at least a month before the study, which was continued
unchanged throughout the trial. Over 6 weeks of selegiline treatment,
subjects were divided into two groups, 39 patients received clozapine and
while 41 patients received risperidone and each group was randomlydivided into three subgroups (for one group Selegiline 5 mg/day, for the
second 10 mg/day, and for the third placebo was added to the regimen).
Patients were assessed through and after 6 weeks by PANSS.
Results: Results: Eight subjects (5 patients in risperidone group and
3 patients in clozapine group) had significant increase in their positive
symptoms and were excluded from the study and 4 patients could not
continue the studyResults: Eight subjects (5 patients in risperidone group
and 3 patients in clozapine group) had significant increase in their positive symptoms and were excluded from the study and 4 patients could
not continue the study because of severe side effects. Mean age of
patients was 47.62 and mean duration of hospitalization was 8.94 years.
In both clozapine and risperidone groups, No significant improvement
was seen in three subgroups (Selegiline 5 mg/day, 10 mg/day, or placebo).
(P=0.684 for risperidone and P=0.479) in clozapin subgroups) No significant difference between clozapine and risperidone groups was observed.
(P=0.893). because of severe side effects. Mean age of patients was
47.62 and mean duration of hospitalization was 8.94 years. In both clozapine and risperidone groups, No
Conclusion: Conclusion: Selegiline was not effective on negative symptoms of schizophrenia for inpatients. This inadequacy was true when
seligiline was added to risperidone, or clozapine.
Results: There are no significant difference in the efficacy between the

two groups, but in the adverse events, the first group was more than second group.
Conclusion: Qing Xin Hao combination with chlorpromazine or clozapine can bring benefit to schizophrenic patients.
References: 1.Bai Han. Textbook of Clinical Psychiatry.China Scinece &
Technology Press. Peking 2006. 2.American Psychiatric association DSMIII-R (1987) Diagnostic and statistical manual of mental disorder, 3rd edn,
revised. APA, Washington, DC. 3.Li Shizhen (1590,Ming Dynasty in China)
Compendium of Materia. The Peoples Medical Publish House (reprint).
Peking, 1999: pp 188-201. 4.Kane, JM. Pharmacologic treatment of
schizophrenia. Biological Psychiatry. 1999,46 (10 ):1396-1408.
P-13-05
ADD on treatment with repetitive transcranial magnetic
stimulation improves negative symptoms in chronic schizophrenia. Preliminary results of a sham controlled study
P-13-07
Tardive dyskinesia in a patient treated with quetiapine
Joachim Cordes
Heinrich-Heine Universitt, Abt. fr Psychiatrie, Dsseldorf, Germany
Introduction: Even after implementation of atypical antipsychotics therapy-resistant negative symptoms are still an important problem. Very few
studies have dealt with the efficacy of repetitive transcranial magnetic stimulation on schizophrenic psychosis so far. Up to now a positive effect of
high-frequency stimulation of the left dorsolateral prefrontal cortex seems
most evident (Hajak et al. 2004). In this study we want to prove the clinical efficacy of rTMS on negative symptoms of partially remitted schizophrenic patients as an add-on therapy.
Methods: 25 patients with predominantly negative symptoms (PANSS
negative-score > 17) were included. They were randomly assigned to a
verum (N=13) and a control group (N=12). Patients in the verum group
received high frequency (10Hz) repetitive transcranial magnetic stimulation over the dorsolateral prefrontal cortex with an intensity of 110%
motor threshold for 10 days (total stimuli 10000). The control group was
treated with a sham coil. Negative symptoms were examined according
to the Positive and Negative Syndrome Scale (PANSS). In addition several
neuropsychological tests were conducted to detect cognitive deficits
(MWTB, TMT, WCST, D2, KAI).
Results: For every parameter the difference between the pre- and the
post-value was calculated. The Mann-Whitney-U-Test showed a significant group-effect on the negative scale of the PANSS (p=0.046). There
was no significant effect on the positive scale. The findings of the neuropsychological tests demonstrated that rTMS treatment did not impair
cognitive performance.
Conclusion: These results confirm our hypothesis, that high frequency
rTMS makes a contribution to the reduction of negative symptoms.
References: Hajak G, Marienhagen J, Langguth B, Werner S, Binder H,
Eichhammer P: High-frequency repetitive transcranial magnetic stimulation in schizophrenia: a combined treatment and neuroimaging study.
Psychol Med. 2004; 34 (7): 1157-63.
P-13-06
A study of Qing Xin I Hao combination with chlorpromazine or clozapine in the treatment of schizophrenia
Bai Han
Shanxi Medical University, Dept. of Biological Psychiatry, Taiyuan City,
Peoples Republic of China
Hao Sun, Peishen Bai
Introduction: To compared the efficacy between Traditional Medicine
(Qingxin Hao) combination with chlorpromazine or clozapine in the
treatment of schizophrenia.
Method: 160 schizophrenic patients were divided into two groups randomly. The first group is treated with Qing Xin Hao combination with
chlorpromazine or clozapine, the second group is treated with chlorpromazine or clozapine. The efficacy was measured with PANSS (positive and
negative symptom scale) and the adverse events were determined with
TESS (treatment emergent symptom scale).
Emmanouil Rizos
Athens University, Medical Psychiatry, Greece
Athanassios Douzenis, Rossetos Gournellis, Christos Christodoulou,
Ioannis Michopoulos, Lefteris Lykouras
Introduction: Quetiapine is an atypical antipsychotic that is believed to
have a low D2 binding affinity in striatal and extrastriatal regions. For this
reason it is associated with low risk for the development of extra pyramidal symptoms (EPS) and tardive dyskinesia and has been tried for the
treatment of tardive dyskinesia in patients with schizophrenia and
schizoaffective disorder.
Method: We report the case of a female patient with the diagnosis of
schizoaffective disorder (using DSM-IV-TR criteria) never treated with conventional antipsychotics.
Results: This patient, initially received amisulpride for three months, discontinued gradually because of persistent and distressing EPS and developed tardive dyskinesia three months later after the initiation of quetiapine.
A trial with ziprasidone resulted in a further worsening of tardive dyskinesia
symptoms. A further trial with aripiprazole, improved these symptoms
witout altering her mental state.
Conclusion: This report offers the opportunity to review the literature
and explore the possibility of quetiapine induced tardive dyskinesia.
P-13-08
A study of Qing Xin I Hao combination with risperidone or
olanzapine in the treatment of schizophrenia
Bai Han
Shanxi Medical University, Dept. of Biological Psychiatry, Taiyuan City,
Peoples Republic of China
Hao Sun, Peishen Bai
Introduction: To compared the efficacy between Traditional Medicine
(Qingxin Hao) combination with risperidone or olanzapine in the treatment of schizophrenia.
Method: 160 schizophrenic patients were divided into two groups randomly. The first group is treated with Qing Xin Hao combination with
risperidone or olanzapine, the second group is treated with risperidone or
olanzapine. The efficacy was measured with PANSS (positive and negative
symptom scale) and the adverse events were determined with TESS (treatment emergent symptom scale)
Results: There are no significant difference in the efficacy between the
two groups, but in the adverse events, the first group was more than
second group.
Conclusion: Qing Xin Hao combination with risperidone or olanzapine
can bring benefit to schizophrenic patients.
References: 1.Bai Han. Textbook of Clinical Psychiatry.Chian Scinece &
Technology Press.2006 1.Bai Han. Textbook of Clinical Psychiatry.China
Scinece & Technology Press. Peking 2006. 2.American Psychiatric association DSM-III-R (1987) Diagnostic and statistical manual of mental disorder,
3rd edn, revised. APA, Washington, DC. 3.Li Shizhen (1590,Ming Dynasty
in China) Compendium of Materia. The Peoples Medical Publish House
(reprint). Peking, 1999: pp 188-201. 4.Kane, JM. Pharmacologic treatment of schizophrenia. Biological Psychiatry. 1999,46 (10 ):1396-1408.
145
P-13-09
Elevated beta2-microglobulin in first-episode, antipsychoticnaive schizophrenia: Evidence for autoimmune pathogenesis
Seetharamaiah Chittiprol
NIMHANS, Neurochemistry, Bangalore, India
Narendran Mavinakayinahalli Neelakantach, Ganesan
Venkatasubramanian, M. N. Naveen, Kurudunje Taranath Shetty,
Jagadisha Thirthalli, B. N. Gangadhar
Introduction: Schizophrenia is a complex neuropsychiatric disorder characterized by delusions, hallucinations, negative symptoms, cognitive
deficits and disorganized behavior. The etiopathogenesis of schizophrenia
has always remained elusive. Autoimmune pathogenesis is amongst the
plausible hypotheses to explain schizophrenia. Previous studies have
shown elevated Y-interferon in schizophrenia patients, which gets
reduced with treatment. The release of 2-microglobulin, the light chain
moiety of the class I major histocompatibility antigens, is facilitated by
Y-interferon. We aimed at examining the levels of serum 2-microglobulin in first-episode, antipsychotic-naive schizophrenia patients in comparison with matched healthy controls.
Method: Forty-five antipsychotic-naive patients [age = 33.07.9 years;
23 males] who fulfilled DSM-IV criteria for schizophrenia were recruited
from the clinical services of the National Institute of Mental Health &
Neurosciences (India) for the study. Healthy comparison subjects [age =
32.57.5 years; 23 males], who volunteered for study, were recruited
from among the hospital staff and their friends. Serum level of
2-microglobulin was quantified in schizophrenia patients and healthy
controls by using Enzyme amplified Immuno Chemiluminiscence method
and the clinical assesment was done using SAPS,SANS and MADRS scales.
Results: Age and sex did not differ between patients and healthy controls
(p > 0.5). Schizophrenia patients [1721.8 405.2 ng/mL] had significantly
higher mean 2-Microglobulin level than healthy controls [1423.0
265.9 ng/mL] (t = 4.1; p < 0.001). The Beta2 microglobulin levels correlated with scores of SAPS,SANS and MADRS scales.
Conclusion: To the best of our knowledge, the findings are the first
report of significantly elevated 2-microglobulin in antipsychotic-naive
schizophrenia patients. Elevated 2-microglobulin could probably be
secondary to Y-interferon activity. The finding supports immune abnormalities in schizophrenia. Since 2-microglobulin has been used as a
marker to assess the progress / prognosis of various immune disorders,
similar utility in schizophrenia requires systematic evaluation.
P-13-10
Long-term adherence and health outcomes study with
long- acting risperidone and oral atypicals in the treatment
of schizophrenia patients lara. An interim-analysis
(ris-sch-4023)
Joerg Czekalla
Bernd Ibach, Ludger Hargarter, Martin Gerwe
Introduction: Two-years naturalistic study investigating adherence to
therapy, tolerability, functionality and quality of life (QoL) of 400 patients
with early schizophrenia under treatment with the only available atypical
depot (Risperdal Consta - RIS-Consta) and other oral atypicals (OATYP).
Method: Planned interim-analysis comprised 179 patients (ITT population; baseline to endpoint). Thereof, 89 patients started treatment with
RIS-Consta, 90 patients with one of six OATYP (11 Olanzapin,
16 Quetiapine, 11 Amisulpride, 16 Ziprasidone, 18 Aripiprazole,
18 Risperidone). Mean age was 32.7 for CONSTA and 34.6 years for
OATYP cohort. Mean duration of schizophrenia (82%: F20.0) was
2.7 years (SD 1.6) for both groups.
Results: There were baseline differences between RIS-Consta and OATYP
cohort with regard to reasons for starting treatment (non-compliance
56% vs 18%; lack of tolerability 22% vs 31%, respectively) and severity
of illness (PANSS total 94 vs 87). With regard to change of therapy, there
was a tendency towards higher retention rates and mean study duration
in the RIS-Consta cohort (56% vs 47%, p=0.23; 395 vs 342 days). PANSS
scores improved significantly for both cohorts (RIS-Consta -17.2 vs OATYP
-16.3). EPS score improved with no significant differences between
cohorts. Overall, reported AEs related to schizophrenia (psychosis 14%;
146
agitation 9.5%) were most common, followed by weight gain (9.5%) and
fatigue (9%).
Conclusion: In this prospective, non-randomized study, interim-analysis
from 45% of 400 planned patients with initial RIS-Consta or OATYP treatment shows comparable improvement of psychopathology and EPS and
a tendency towards higher treatment adherence with RIS-Consta, considering initially more non-compliant patients in this group.
P-13-11
Malondialdehyde levels in stable chronic schizophrenic
patients
Armando Morera
University of La Laguna, Psychiatry, Spain
A. Intzausti, P. Abreu, M. Henry, A. Orozco, E. Diaz-Mesa, D. HernandezGarcia, C. Borges-Gargano, M. M. Calvo-Malvar, A. Benitez-Estevez
Introduction: Malondialdehyde MDA) is a common biologic marker of
oxidative stress used in schizophrenic research. Data regarding MDA levels
in schizophrenic patients are controversial. Our objective is to study MDA
level in schizophrenic patients.
Method: The sample was comprised by 23 stable chronic schizophrenic
patients. None of them had a history of medical or neurological disease
and routine laboratory parameters were normal. The study was carried
out in accordance with the Helsinki Declaration and all subjects gave written
informed consent before their inclusion. Blood samples were extracted
between 8:30 and 9:00 after fasting in July and January. The same routine was followed during the two experimental sessions. Serum MDA was
determined by the thiobarbituric acid reactive substance (TBARS), according to the method of Ohkaba et al (1979).
Results: The sample was comprised by 15 male and 8 female schizophrenic patients (age 42.815.4 vs 54.916.2, p=0.106). There were no
differences in MDA levels between men and women in January or July
(data not shown). There was no relation between age and MDA levels in
July or January (data not shown). Plasma MDA levels was significantly
higher (p<0.02) in July than January (2.51.21 vs 1.60.51).
Conclusion: MDA has a circannual rhythm of formation with higher levels
in July and lower levels in January. This variation in seasonal MDA levels
should be accounted when researching in this field.
P-13-12
Time to clincal stabilization and discharge from hospital
treatment of patients with schizophrenia after conversion
to long-acting risperidone - results of a prospective naturalistic study
Bernd Ibach
Ludger Hargarter, Martin Gerwe, Joerg Czekalla
Introduction: Evaluation of the initial treatment course in patients with
schizophrenia after transition to long-acting risperidone (RisperdalConsta - RIS-Consta) treatment under clinical routine conditions seems
important for the understanding of long-term disease stability.
Method: Pretreated moderate to severely ill (CGI) in-patients with schizophrenia were switched to a two-week intervall application of RIS-Consta.
Assessment included reasons for transition, co-medication, PANSS,
NOSIE, AE and EPMS. Study completion criteria were clinical stability
under treatment with RIS-Consta and/or discharge within or a maximum
observational period of 12 weeks. Criteria for stable adjustment were (1)
RIS-Consta was the only high potency/second generation antipsychotic
drug, (2) stable or improved CGI, (3) stable RIS-Consta dosage since previous visit.
Results: 290 patients were documented (56.2% male). Mean age was
40.3 years. Causes for transition were insufficient efficacy (46.9%), tolerability (13.8%), compliance (70.4%) and initiation of long-term treatment (70.34%). At discharge n=123 (43.8%) patients were judged as
clinically stable (S), n=167 (56.2%) as not stable (NS). Median duration of
hospitalization for S-group were 42, in the NS-group 28 days. PANSS and
NOSIE revealed clinical and psychosocial amelioration in favour of
S-group. EPMS were the most common AEs observed in both groups,
although total EMPS-score improved during the observational period (in
approx. 63%). Variables that correlated with the given definition for stability at baseline were not identified.
Conclusion: The observation of a shorter stay in hospital for clinically not

stabilised patients with schizophrenia may be due to several factors
[e.g. higher need of patients for discharge (prior to remission) leading to
revolving door effect, low potential for long-term remission, lack of
therapeutic adherence, pressure of external health care providers]. These
results raise the question, whether extended hospitalization of NSpatients may foster clinical stability. Moreover, this prospective study suggests effectiveness and improved tolerability (EPMS) of RIS-Consta in
moderate to severely ill patients with schizophrenia.
P-13-13
Aspects of relationships between schizophrenia - antipsychotics and diabetes mellitus
Gavril Cornutiu
Clinica De Psihiatrie, Oradea, Romania
Gheorghe Paina, Vasile Vladut, Oana Cornutiu
Introduction: AIM: To analyze the relationship between schizophrenics
(SCH), antipsychotics and diabetes mellitus ( DM ) according to the levels
of inherited diabetic vulnerability
Method: We studied a group of 336 SCH, 262 treated with classical neuroleptics( CN ), 74 treated with atypical neuroleptics( AN ). Here: olanzagine, risperidone, serognal and lezonex. Criteria of admittance: a.) diagnosis criteria from DSM-IV-R. b.) debut and treatment for at least two
years. c.) we considered diabetic schizophrenics only those patients who
got diabetes after being diagnosed with SCH and started treatment.
Levels of intensity of the hereditary diabetic vulnerability were considered:
a.)Parents with mellitus diabetes. b.)Other relatives with sugar diabetes.
Results: Prevalence of DM:a.-General population-2.3%,b.All SCH1.9%,c.SCH treated with CN-1.14%,d.SCH treated with AN1.13%,e.SCH with DM parents-6.25%,f.SCH with other relatives with
DM-0%,g.SCH without DM relatives-1.12%
Conclusion: 1.In this group the likelihood of SCH to become associated
with DM is smaller than in general population. 2.Neuroleptics (both CN
and AN) do not increase the DM risk in this group. 3.In this group there
is no risk difference between CN and AN. 4.In this group the risk of SCH
to be associated with DM does not lie in the antipsychotic treatment but
in the parental hereditary baggage. 5.We do not yet know if this risk is
enforced by the evolution of the disease or by the antipsychotic treatment
or by both together. 6.There is the possibility that other studies in other
groups should involve other risks factors to trigger DM. 7.In our opinion,
the antipsychotics are not a cause for developing DM; they merely mark
and enhance the vulnerability of the patients. It is likely for this process to
work in other idiosyncrasies as well. 8.The result is the demand to monitor the specific vulnerable cases, both inherited and gained. KEY WORDS:
schizophrenia, antipsychotics, diabetes mellitus
References: REFERECES: 1.Serenyak M.J. Association of Diabetes
Mellitus with Use of Atypical Neuroleptics in the Treatment of
Schizophrenia, Am.J. Psychatry, 2000, Apr, 159 ( 4). 2.Ebminam M.
Cmparative Study of the Development of Diabetes Mellitus in Patients
Taking Risperidone and Olanzagine, Pharmacology, 2003, 23 (8); 10371042.
P-13-14
Efficacy and safety of ziprasidone in the treatment of
schizophrenia in adolescence
Daniela Petric
Clinical Hospital Center, of Psychiatry, Rijeka, Croatia
Tanja Franciskovic, Mirnjana Graovac
Introduction: Ziprasidone is an atypical antipsychotic with a high ratio of
5-HT(2A) to D(2) receptor antagonism. It is also an agonist at 5-HT(1A). In
consideration with acceptable phafmacologic profile and rare side effects,
ziprasidone could be the first choice for tretament of schizophrenia in
adolescence. This report describes treatment with ziprasidone in four
adolescents with severe psychotic illnness who had unsuccessful trials of
alternative antipsychotic medications. So far there are few studies on efficacy of ziprasidone in adolescent patients with schizophrenia.
Method: During the 3-month period 4 patients with confirmed
diagonose of Schizophrenia in accordance to DSM-IV, (2 boys and 2 girls,
in age of 16 and 17) previously treated with atypical antipsychotics
(risperidon, olanzapin, quetiapin). Because of serious side effects and lack

of ineffciant therapy was switched to ziprasidone. Medium therapeutic
dose of ziprasidone was 130 mg ( in range 80 - 160 mg). The scales for
clinical evaluation were: PANSS (Positive and Negative Syndrome Scale),
CGI - S (Clinical Global Impression Severity Scale), CGI - I (Clinical Global
Impression Improvment Scale), CGAS (Childrens Global Assessment
Scale), PQ-LES- Q (Pediatric Quality of Life Enjoyment and Satisfaction
Questionnaire). We applied scales at the moment ziprasidone was introduced, after 1 month and 3 month.
Results: Treatment with ziprasidone resulted with decrease of psychotic
symptoms. General functioning and compliance with the treatment has
been improved. Side effects through this period were not noticed. Only
one patient has not improved (halucinating experience, telepathic phenomens, phenomens of depersonalisation were still present). In this case
we added risperidon to ziprasidone, only this patient needed additional
antipsychotics for positive symptoms.
Conclusion: The first experience with ziprasidone in adolescent with
schizophrenia showed promising results. Further research is needed to
prove our first impression.
References: (1) Masi G, Mucci M, Pari C. Children with schizophrenia:
clinical picture and pharmacological treatment. CNS Drugs.
2006;20(10):841-66. (2) Jensen PS, Buitelaar, J Pandina GJ, Binder C,
Haas M. Management of psychiatric disorders in children and adolescents
with atypical antipychotics. Eur Child Adolesc Pscyhiatry. 2006 Oct 30. (3)
Meighen KG, Shelton HM, McDougle CJ. Ziprasidone treatment of two
adolescent with psychosis. J Child Adolesc Psychopharmacol. 2004
Spring;14(1):137-42.
P-13-15
Amisulpride augmentation of clozapine in chronic schizophrenia: A randomized, placebo-controlled, prospective
trial
Hans-Jrg Assion
Westphalian Center, Psychiatry and Psychotherapy, Bochum, Germany
Sebastian Lemanski, Hartmut Reinbold
Introduction: Only limited data is available on the effectiveness of augmentation with antipsychotics to partially responding clozapine therapy in
chronic schizophrenia. Amisulpride has a binding profile that is complementary to the profile of clozapine and the combination of both substances has proven to be beneficial in single case reports or open label
studies. We conducted a placebo-controlled, randomized, prospective
trial to further evaluate the efficacy and safety of a combination of
amisulpride and clozapine.
Method: 16 patients with DSM-IV diagnosis of chronic schizophrenia and
persisting symptoms under clozapine treatment were included in the
study. All patients filled in informed consent. Patients were kept on a stable dose of clozapine throughout the 6-weeks, prospective trial. They randomly received either combined clozapine and placebo (4 patients) or
clozapine and amisulpride (400 or 600 mg/day, 12 patients). Assessments
were GAF, CGI, BPRS and ESRS. Amisulpride and clozapine serum levels
were taken at the beginning, after 3 weeks and at the end of the study.
Statistical analyses were performed using LOCF and t-test.
Results: Patients with combined clozapine and amisulpride significantly
improved in the outcome measures of BPRS ratings at endpoint compared
to combined clozapine and placebo. Correspondingly, CGI and GAF were
in favour for the combination therapy with amisulpride and clozapine.
The higher dose range of amisulpride was more beneficial than the lower
dose range. No severe side-effects occurred throughout the study in any
of the treatment arms.
Conclusion: Administration of amisulpride for augmentation of clozapine substantially improves symptoms in chronic schizophrenia in a group
of patients, partially or non-responsive to clozapine treatment. The combination is well tolerated without major side-effects. Further randomized
trials are necessary to evaluate the efficacy of combined antipsychotics in
chronic schizophrenia.
References: 1. Munro J, Matthiasson P, Osborne S, et al. Amisulpride
augmentation of clozapine: an open, non-randomized study in patients
with schizophrenia partially responsive to clozapine. Acta Psychiatr Scand
2004;110:241-242 2. Lerner V, Bergmann J, Borokhov A. Augmentation
of amisulpride for schizophrenic patients nonresponsive to antipsychotic
monotherapy. Clin Neuropharmacol 28:66-71
147
P-14
Psychotic Disorders IV
P-14-01
Computer-based cognitive training in schizophrenia:
a pilot test of gradior
Juan Carlos Ruiz
Universidad de Valencia, Metodologia cc. Comportamiento, Spain
Maria Jose Soler, Carmen Dasi, Pilar Tomas
Introduction: Deficits in attention/vigilance, working memory, verbal and
visual learning and memory, executive functioning, and reasoning and
problem solving are core cognitive deficits of schizophrenia.
Method: Ten patients with schizophrenia, mean age (37), illness onset
mean (16), participated in a computer-based cognitive training program
(GRADIOR) designed to improve cognition in schizophrenia. This program
trains the different cognitive domains impaired in schizophrenia with specific tasks that can be adjust in difficulty depending on the progress of the
patients. A battery of neuropsychological tests was selected to assess cognition before and after the training program intervention.
Results: Improvements in cognition have been significant only in some of
the specific scores used to measure attention and executive functioning.
Performance on the training exercises showed progress but in many tasks
patients show ceiling effects. There are difficulty levels that patients cant
surpass just with the simple repetition of the task.
Conclusion: The computer-based cognitive training program (GRADIOR)
results did not show a global cognitive improvement in patients with
schizophrenia. Performance in the specific trained tasks revealed progress
up to a specific difficulty level that patients cant overcome. Findings in
this pilot study suggest that the simple repetition of the cognitive tasks
employed in the program, do not imply improvements in the neurocognitive deficits of the patients.
References: Bellack, AS; Dickinson, D; Morris, SE; Tenhula, WT. (2005).
The Development of a Computer-Assisted Cognitive Remediaton Program
for Patients with Schizophrenia. Israel Journal of Psychiatry and Related
Sciences, 42(1), 5-14. Bozikas, V.P.; Kosmidis, M.H.; Kiosseoglou, G. y
Karavatos, A. (2.006). Neuropsychological profile of cognitively impaired
patients with schizophrenia. Comprehensive Psychiatry, 47, 136-143.
Twamley, E.W.; Jeste, D.V. y Bellack, A.S. (2.003). A Review of Cognitive
Training in Schizophrenia. Schizophrenia Bulletin, 29, 359-382.
P-14-02
A case-control family study of schizophrenia and related
disorders
Linda Kader
Sunshine Hospital, AMHRU, Psychiatry, St Albans, Australia
B. M. Tripathi, Rajesh Sagar
Introduction: This study aims to assess the psychiatric morbidity among
the first degree relatives (FDRs) of patients with schizophrenia and related
disorders using family history method in an Indian sample.
Method: 126 cases were included from outpatient clinic and interviewed
using SCAN (Schedule for Clinical Assessment in Neuropsychiatry) for
diagnoses as per ICD-10. 113 had a diagnosis of schizophrenia and
13 had a diagnosis acute and transient psychotic disorder (ATPD). Key
informants were interviewed using Family Interview for Genetic Studies
(FIGS). 130 Controls were selected from the surgical outpatient clinic.
Chi-square test, students t test as appropriate was used. Odds ratio and
95% confidence interval to determine association between risk factors
(i,e positive family history for psychiatric disorders) and the outcome (disease status) were calculated. Morbidity risk for developing different disorders was calculated
Results: Data obtained about 113 case with schizophrenia and 13 with
ATPD and their FDRs (798 FDRs of cases and 1050 FDRs of controls). The
majority in both groups were aged 25-34 years. Mean duration of illness
for cases was 5.010 years (SD=4.872) before presentation to clinic.
24.6% cases with schizophrenia and acute psychosis had family history of
psychiatric disorders in their FDRs, whereas 18.4% controls had such a
148
history (p=0.023). The commonest disorder among the FDRs of cases was
schizophrenia. Other disorders are bipolar disorder, depression and substance abuse disorder. The siblings of schizophrenics are at a greater risk
of developing schizophrenia as compared to the siblings of controls
(OR=4.4 (95% CI=1.226-16.190).
Conclusion: A spectrum of psychiatric disorders occur in FDRs ranging
from non-affective to non-affective disorders and also neurotic disorders.
This study adds to the available literature and data on the familial basis of
schizophrenia and also replicates the finding shown earlier that among
the first degree relatives, siblings are the most at-risk of developing the
disorders
References: 1. Andreasen NC, Endicott J, RL Spitzer, et al. The family history method using diagnostic criteria. Arch Gen Psychiatry.
1977;34:1229-1235 2.Kendler KS, McGuire M, Gruenberg AM, et al. The
Roscommon family study. I. Methods diagnosis of probands, and risk of
schizophrenia in relatives. Arch Gen Psychiatry. 1993; 50: 527-540
3.Kendler KS, McGuire M, Gruenberg AM, et al. The Roscommon family
study II. The risk of non schizophrenic non affective psychosis in relatives.
Arch Gen Psychiatry. 1993; 50: 645-652
P-14-03
Indicators of schizophrenia-associated immune system
alterations
Aren Khoyetsyan
Inst. of Molecular Biology, Macromolecular Compl., Yerevan, Armenia
A.S. Boyajyan, G.V. Tsakanova
Introduction: Schizophrenia, as immune-based neurodevelopmental
pathology, is characterized by alterations of both the innate and adaptive
immunity. However, the molecular pathomechanisms responsible for
these alterations have not been studied well. We investigated the involvement of the major mediators of the immune response, autoimmunity and
related apoptosis, notably the complement system and cryoglobulins
(Cgs), in the pathogenesis of schizophrenia. Complement system is a cascade of over 30 activating, effector, and regulatory proteins that represents an innate arm of immune defense. On the other hand, Cgs is a nonspecific marker of the activation state of the immune system, inflammatory and autoimmune processes. Furthermore, these abnormal immune
complexes, where both antigen and antibody are presented by
immunoglobulins, may bind complement components and activate complement.
Method: Sixty eight patients with paranoid form of schizophrenia (ICD-10)
and age and sex matched fifty two healthy volunteers as well as comparison group, were involved in this study. Cgs were isolated by exposure of
the blood serum samples to precipitation at low temperature followed by
extensive washings of Cg-enriched pellets. Total concentration of protein
in Cgs was determined according to the method of Lowry et al. The
immunochemical composition of Cgs was analyzed using different electrophoretic and immunoblotting systems. A hemolytic assay was based
on the standard 50% complement hemolysis test for both the classical
and alternative pathway of human serum complement. For data analysis
ordinal descriptive statistics and the Mann - Whitney U test were used.
Results: Our results demonstrated elevated levels of both the complement system activity (classical and alternative pathways) and type III Cgs
in schizophrenia-affected patients. We also revealed the presence of C1q
and C3 complement proteins and their activation products in Cgs isolated
from the blood of schizophrenia-affected subjects.
Conclusion: Based on the result obtained we concluded that Cgs are
responsible for the activation of complement system via the classical and
alternative pathways and development of autoimmune reactions in
schizophrenia.
P-14-04
RP-C4-CYP21-TNX modular complement c4 genotypes in
schizophrenia: A pilot study
Karine Mayilyan
Institute of Molecular Biology, Yerevan, Armenia
Danial R. Weinberger, Yee-ling Wu, Bi Zhou, C. Yung Yu
Introduction: A recent rank-based genome scan meta-analysis [Lewis et
al. Am J Hum Genet, 2003;73:34-48] revealed several suggestive schizo-
phrenia (SCH) susceptibility loci, including 6p22.3-6p21.1. C4 genes (C4A

and C4B) together with the serine/threonine nuclear kinase gene RP, the
steroid 21-hydroxylase CYP21, and the extracellular matrix protein TNX
form a genetic unit, the RP-C4-CYP21-TNX (RCCX), located on the HLA
class III region (6p21.3). We have performed a case-control association
study to investigate C4 genes RCCX variations, to test the hypothesis that
C4B deficiency contributes to risk of SCH.
Method: 31 healthy volunteers (HV) vs. 31 schizophrenic patients (SP)
were recruited from an Armenian population. Southern blot analysis
[Chung et al. Curr Prot in Immunology, 2005] with Taq I; PshAI and Pvu II
restriction enzymes were used to determine the RCCX modularity, C4,
CYP21 and TNX genes total dosage and isotypes, C4 long and short
genes and their duplications. C4 allotyping was performed according to
Sim and Cross. [Biochem J, 1986;239:763-7]. An immunodiffusion
method was applied for serum C4 quantitation. Two types of C4 gene
nonsense mutations were examined as well: 1. a 2-bp (GT) deletion in
codon 497 of exon 13; 2. a 2-bp (TC) insertion in codon 1213 of exon 29.
Results: About one third of 62 subjects had three-modular RCCX at least
on one chromosome, therefore, 5 or 6 C4 genes in total. Nine subjects
had rearrangement in the RCCX modules that is characterized by the
CYP21B-CYP21B configuration, and an unusual version of TNX gene.
None of subjects had monomodular-short RCCX that is characterized by
HLA haplotype A1B8DR3. Interestingly, there was a 2.6 fold difference in
the frequency of the C4B deficiency between groups: 26% SP vs. 10%
HV. However, none of SP had the homozygous deficiency of C4B reported by Rudduck et al. [Hum Hered, 1985;35(4):223-6]. Notably, no subject
had any nonsense mutations, even of the second type, which is very common in Caucasian populations.
Conclusion: Our results suggest a possible association of the C4B deficiency with SCH susceptibility. In SCH, C4B deficiency could occur due to
gene deletion and/or C4A homo-expression, but not because of C4B nonexpression. The study will be expended, and ~250 SP vs. 250 HV will be
investigated. KM thanks Fulbright Association for # 68430064 fellowship.
P-14-05
Association study of brain-derived neurotrophic factor
Val66Met polymorphism and the severity of psychopathology in schizophrenia
San-Yuan Huang
Tri-Service General Hospital, Psychiatry, Taipei, Taiwan
Hsin-An Chang, Chuan-Chia Change, Chih-Lun Chen, Wei-Wen Lin,
Mee-Jen Shy
Introduction: Brain-derived neurotrophic factor (BDNF) belongs to the
neurotrophic factor superfamily and has been proposed as a risk factor
for schizophrenia. The aim of this study was to examine the relationship
between the BDNF Val66Met polymorphism and schizophrenia as well as
its severity of psychopathological symptoms.
Method: We recruited 251 schizophrenic patients and 285 normal controls matched for gender, age and ethnicity. Each patient was initially
evaluated by one experienced attending psychiatrist and then interviewed
by a well-trained psychologist using the Chinese Version of the Modified
Schedule of Affective Disorder and Schizophrenia-Life Time (SADSL) to
reach the DSM-IV diagnosis of schizophrenia. Genotyping of the BDNF
Val66Met polymorphism was performed with a PCR-RFLP method and
reconfirmed by a direct sequencing technique.
Results: No significant differences were found between the patients and
healthy controls in genotype distributions and allele frequencies of the BDNF
Val66Met polymorphism. There were also no significant differences between
more homogenous schizophrenic subgroups and normal controls. There
were significant differences in global (p=0.018), general (p=0.04) and
especially negative (p = 0.005) symptom scores of PANSS among three
genotype groups in acutely exacerbated schizophrenic patients.
Conclusion: This study indicates that although the BDNF Val66Met polymorphism may not confer genetic risk for schizophrenia and its clinical
subtypes, it appears to influence severity of psychopathological symptoms
in acutely exacerbated schizophrenia in the Han Chinese population.
Further replication studies are necessary to re-examine the effect of the
BDNF Val66Met polymorphism in relation to longer time course of schizophrenia, including treatment response to antipsychotics.
References: 1. Arnold SE, Rioux L. Challenges, status, and opportunities

for studying developmental neuropathology in adult schizophrenia.
Schizophr Bull 2001;27:395-416. 2.Takahashi M, Shirakawa O, Toyooka
K, et al. Abnormal expression of brain-derived neurotrophic factor and its
receptor in the corticolimbic system of schizophrenic patients. Mol
Psychiatry 2000;5:293-300. 3. Nanko S, Kunugi H, Hirasawa H, et al.
Brain-derived neurotrophic factor gene and schizophrenia: polymorphism
screening and association analysis. Schizophr Res 2003;62:281-3.
P-14-06
Clinical decision-making during five years of anti-psychotic
treatment
Sten Levander
Lund University, Department of Clinical Science, Malm, Sweden
Jonas Eberhard, Eva Lindstrm
Introduction: Explore how clinicians select drug treatment based on symptoms, side effects and patient factors, including patient participation in the
process, and the association between these factors and attitudes to drugs.
Method: A cohort of 166 patients initially treated with risperidone was
followed with yearly assessments over 5 years. At study end-point 101
patients were evaluated of whom 58 were still treated with risperidone.
Results: More women than men remained in the study, and on the initial
medication. Most common reason for switch was lack of efficacy.
Clinicians and patients agreed well in their global ratings of medication
effects, and side effects. Robust associations between switch decisions
and patient characteristics including symptoms and side effects could not
be identified. The effects of switches were rated higher by the clinicians,
than by the patients. Negative drug attitudes were associated with pronounced positive symptoms (threshold effect) whereas the association
with lack of judgement and insight was linear over the whole range.
Conclusion: The decision-making process appears to have many
unknown components, and may benefit from more active patient involvement by using structured clinician and patient rating scales for monitoring
the treatment. Such shared decision-making may improve compliance.
P-14-07
The influence of polymorphism for Regulator of G-protein
signaling 4 (RGS4) on regional brain metabolism (18FDG
PET) and phenotypic variables in schizophrenia
Jiri Horacek
Prague Psychiatric Centre, Prag, Czech Republic
Filip Spaniel, Tomas Novak, Martin Brunovsky, Milan Kopecek, Cyril
Hoschl
Introduction: RGS4 represents a positional and functional candidate
gene for schizophrenia confirmed by several studies in independent samples.
Method: In a group of 63 patients with schizophrenia, we have genotyped four SNPs (1, 4, 7, 18) which have previously been associated with
schizophrenia, individually or as part of haplotype. We evaluated the
influence of candidate SNPs on phenotypic characteristics and regional
brain metabolism measured by 18FDG PET. Neuroimaging data were
treated by SPM99.
Results: We found lower metabolism bilaterally in basal ganglia (p 0.05,
corrected) in the risky G-allele carriers in SNP 7. In SNP 1, the trend for
lower metabolism associated with the G-allele in the right prefrontal cortex was detected (p 0.001). The risky G-allele was connected with lower
expression of negative symptoms (SNP 7) and later onset of schizophrenia
(SNP 7, 18).
Conclusion: Our results support the role of basal ganglia and the prefrontal cortex in the mechanism of how the RGS4 polymorphism influences schizophrenia. We formulate the hypothesis of specific RGS4 phenotype of schizophrenia characterized by the lower expression of negative symptoms and later onset which differs from the schizophrenia subtypes associated with candidate genes regulating neurodevelopment and
synaptic structure. The research was supported by the grants NR8792-3
IGA MZ CR and 1M0517 MSMT CR.
149
P-14-08
Parkisonism and transcranial ultarsound as markers of
schizotaxia in an indigenous population of Argentina
Gonzalo Guerrero
Instituto de Psicopatologia, JUJUY, San Salvador de Jujuy, Argentina
Gonzalo Guerrero, Nstor Florenzano, Eduardo Padilla, Mara Calv,
Federico Micheli, Mercedes Bourdieu, Gabriela Gonzalez Alemn, Sergio
Strejilevich, Javier I. Escobar, Horacio A. Conesa and Gabriel A.de
Erausquin
Introduction: Schizophrenia is a complex trait that receives many contributions from genetic and environmental influences. Unaffected relatives
of patients with schizophrenia may display intermediate phenotypes that
mark a non penetrant genetic diathesis for schizophrenia. Parkinsonism is
common in patients with newly diagnosed untreated schizophrenia, but
its presence in first degree relatives has not been studied. Substantia
Nigra hyperechogenicity is a good marker of damage to dopaminergic
neurons, and of vulnerability to parkinsonism.
Method: We evaluated movement abnormalities and transcranial ultrasound in 36 patients with untreated schizophrenia (IS), their unaffected
first degree relatives (FDR) and normal population controls in a Kolla
indigenous population. Diagnosis was ascertained with SCAN, parkinsonism with UPDRS and motor planning and performance with Purdue
Pegboard Test.
Results: IS had significant motor impairment on UPDRS. FDR had significantly more motor impairment than controls on UPDRS scores. IS also had
significant impairment on the Purdue pegboard task, and FDR had significantly more impairment than controls, which was statistically significant
with either hand alone. The area of echogenicity was larger on the left
substantia nigra of IS, but this difference did not reach statistical significance. On the right substantia nigra IS had a twofold increase on the
average echogenic area. FDR had echogenic areas intermediate between
index subjects and controls and significantly different from the latter.
Prediction of diagnostic class based on motor impairment and echogenicity.
When only the UPDRS and Purdue scores were used, multivariate analysis
of the sample by discriminant analysis using group assignment (IS, FDR,
control) as classification criterion yielded two discriminant functions
explaining 99.1 and 0.9 % of the total variance respectively. Effectively,
the first discriminant function explained all of the classification data
(p=0.000). Reclassification using scores of the discriminant variable
allowed correct forecasting of the class assignment of 64.1% of the subjects. If transcranial ultrasound data were included in the discriminant
analysis, the proportion of variance explained by the two discriminant
functions changed to 93.1 and 6.9% respectively. The number of correctly classified original cases increased to 69.4%, primarily on account of a
greater number of correctly classified siblings, without much loss on the
ability to forecast assignment to either the IS or the controls groups.
Conclusion: We propose that a specific vulnerability of dopaminergic
mesocortical projection during development provides a substrate for gene
environments interactions and can be used as an endophenotype.
References: Caligiuri ,(1993). Am J Psychiatry. 150(9):1343-8
P-14-09
Cathepsin K - an unforeseen player in the game of
schizophrenia
Hans-Gert Bernstein
University of Magdeburg, Psychiatry, Germany
A. Bukowska, H. Dobrowolny, B. Bogerts, U. Lendeckel
Introduction: Among the rat genes the cerebral expression of which is
altered by neuroleptics in one direction and by amphetamine in the opposite direction, there are only three that are located in (human) chromosome regions known to be linked to schizophrenia (Ko et al. 2006).
Interestingly, one of them, the lysosomal cysteine protease cathepsin K
(cath K) is commonly thought not to be expressed in the central nervous
system.
Method: We studied the presence of cath K and its cellular localization
in rat and human brains. Human brains were from the New Magdeburg
Collection. Three cases of schizophrenia and three controls were subjected to Western blot analysis, six of either group to immunohistochemistry. All schizophrenics had longterm medication with neuroleptics.
Human ossifying finger bone served as positive reference tissue.
150
Results: Western blot analysis (human heart and brain specimens) revealed one strong band of predicted size (37kDA, procath K). Cath K was
found to be widely distributed throughout rat and human brain, with
neurons being the mejor cellular site of expression. Strong immunolabeling was seen in the hypothalamus, the striatum and the cerebellum.
Importantly, compared to matched controls there was a clear upregulation
of cath K expression in brains of schizophrenics.
Conclusion: Our data show that cath K is constitutively expressed in
mammalian brain. The sharp upregulation in schizophrenia might be due
to medication. Its location on chromosome 1q21, however, makes the
protease a promising candiate for further studies. Increased activities of
cath K might contribute to the frequently reported osteoporosis in schizophrenia (Bernstein et al. 2006), since cath K is a major regulator of
bone density. Supported by Stanley and NBL-3
References: Ko F, Tallerico T, Seeman P. 2006, Synapse 60, 141151.Bernstein H-G, Bukowska A, Dobrowolny H, Bogerts B, Lendeckel U.
2006. Synapse in press
P-14-10
Dehydroepiandrosterone and cortisol in patients with
residual schizophrenia
Svetlana Ivanova
Mental Health Research Inst., Cellular and Molecular Biology, Tomsk,
Russia
Arkady Semke, Olga Fedorenko, Valentin Loginov, Elena Kornetova
Introduction: Dehydroepiandrosterone (DHEA) or their sulfate conjugate
(DHEAS) exert multiple effects in the central nervous system, and may be
involved in the pathophysiological processes in schizophrenia. Also
according to literature data, dehydroepiandrosterone is associated with
clinical symptoms and conducted treatment (Silver H et al,2005). This
study aimed to identify concentration of hormones of dehydroepiandrosterone sulphate and cortisol in patients with residual schizophrenia in the
process of therapy with atypical neuroleptic.
Method: 20 patients with residual schizophrenia have been examined in
dynamic of treatment with atypical neuroleptic quetiapine. Duration of
schizophrenic disorder constituted not less than 5 years. At baseline and
6 week later of pharmacotherapy in patients concentration of cortisol
and DHEA(S) was identified in serum of blood. The control group was
constituted by 30 mentally and somatically healthy persons.
Results: In common group of patients with residual schizophrenia trend
toward increase of cortisol concentration was observed, DHEA(S) concentration did not differ from control. According to results of assessment of
efficacy of conducted pharmacotherapy assessed according to scale CGI ,
patients were divided into two groups: in 15 patients high efficacy of the
therapy has been noticed (group 1), in 5 persons (group 2) insignificant
improvement. In patients with low efficacy of the therapy reliable
decrease of DHEA concentration has been revealed both as compared
with healthy persons and as compared with group 1 (1,320,07 pkg/ml,
2,550,41 pkg/ml in healthy persons, p<0,05) and correlation DHEA/
cortisol
Conclusion: Decrease of neurosteroid DHEA(S) is prognostically adverse
sign in relation to prognosis of efficacy of the therapy. Informative is not
only identification of the level of DHEA but also assessment of correlation
of dehydroepiandrosterone and cortisol characterizing state of anabolic
and catabolic processes (stress limiting and stress realizing systems) of the
organism of the patient and conditioning responsiveness to pharmacotherapy. Identification of hormonal indices before administration of
pharmacotherapy allows consideration them as predictors of clinical efficacy of conducted therapy and use as complimentary paraclinical methods
of examination.
References: Silver H, Knoll G, Isakov V, Goodman C, Finkelstein Y. Blood
DHEAS concentrations correlate with cognitive function in chronic schizophrenia patients: a pilot study. J Psychiatr Res. 2005 Nov;39(6):569-75
P-14-11
Amino acid transport systems in fibroblasts from schizophrenic patients and healthy controls
Nikolaos Venizelos
rebro University, Clinical Medicine, Biomed., Orebro, Sweden
Ravi Vumma, Flyckt Lena, Lars Bjerkenstedt, Frits-Axel Wiesel
Introduction: Human fibroblast cell cultures offer an excellent model for
experimental studies on the transportation of amino acids across cell
membranes. New knowledge regarding transporters and their substrates
motivated us to further characterize the amino acid transporters. The
inhibiting effect of alanine on tyrosine transport can be assigned to several tyrosine transporters, including systems L and A [1]. The specific aim
of this study was to investigate and elucidate the importance of two
major transporters, the L- and A-Systems and their isoforms LAT1, LAT2,
LAT3, LAT4 and ATA2 for A-system in transport of tyrosine and alanine in
fibroblast cells from patients with schizophrenia and controls.
Method: Fibroblast cell lines, (n=6) from healthy volunteers and (n=6)
from patients with schizophrenia, were included in the study. Uptake of
[L-14C]-tyrosine and [L-14C]-alanine in fibroblasts was measured by using
the cluster tray method in the presence or absence of high concentrations
of specific inhibitors.
Results: Of the total uptake, 90% of tyrosine and 65 % of alanine were
transported through sodium-independent L-system, and 10% of tyrosine
and 75 % of alanine were transported by the A-system. The LAT1-isoform
of the L-system showed to be the major transporter of tyrosine in fibroblasts.
Conclusion: Human fibroblast and human brain micro-vascular endothelial cells (hBME) [2] are shown to have LAT1 as major transporter of tyrosine in common. There seems to be existence of competition between
alanine and tyrosine for transport across membranes. The findings of this
study confirmed that cultured human fibroblasts provide an advantageous system to study the transport mechanism of amino acids across the
plasma cell membrane and seems to be the most near relavant human
model for studying amino acid transport defects at BBB.
References: [1]. Olsson E, Wiesel FA, Bjerkenstedt L, Venizelos N.
Neurosci. Lett. 393: 211-5 (2006). [2]. Umeki N, et al. Drug Metabol.
Pharmacokin. 17(4): 367-373 (2002).
P-14-12
The patient-specific mutations on the gene or flanking
gene in monozygotic twins discordant for schizophrenia
induced by retoroposon Alu
Shinichiro Nanko
Teikyo USM, Psychiatry, Tokyo, Japan
Akihisa Akahane, Takanori Hata, Hiroko Saito, Mikako Ueno
Introduction: Mobile elements, which are repetitive elements, have
brought a major impact on genomic and chromosomal diversity. One of
the well-known human mobile element, retroposon Alu, is about 300bp
segments that is able to move around in the human genome, perturbing
construction and expression of neighboring genes, leading to human
genomic diversity and various diseases. Methylation suppresses the Alu
retroposition, but this system is unstable during the stage of development
or under stress conditions. In the field of psychiatry, retroviral-related
sequence in monozygotic twins discordant for schizophrenia was isolated
and was found to be aberrantly-methylated. Thus, we speculated that the
behavior of mobile elements may affect the gene responsible for schizophrenia under low or aberrant methylation. Based upon this hypothesis,
we attempted to investigate the distribution of Alu insertion sites to
develop a better understanding of the etiological roles of the mobile elements in human genome. Here, we report the patient-specific mutations
from de novo Alu insertion on flanking gene in monozygotic twins discordant for schizophrenia.
Method: We attempted to detect the de novo insertion sites of Alu in
genomic DNA from one pair of monozygotic twins discordant for schizophrenia (patient with schizophrenia and her sister) using Alu specific
inverse-PCR with subtraction-screening and DNA walking. This study was
done under the approval of the Ethical Committee for Genetic Research,
Teikyo University School of Medicine.
Results: From screening Alu insertion, we detected patient-specific fragments which may contain the susceptible genes or regions for schizophrenia.
One of these patient-specific fragments containing Alu insertion was
located on 3-flanking regions of gene. Both sides of this patient-specific
fragment were detected by DNA-walking analysis. From the results, duplication of 3-flanking regions of gene was discovered flanking the patientspecific mutation with Alu insertion.
Conclusion: We discovered de novo Alu retroposition occuring on flanking gene of the patient. This induced duplication may indicate the contribution of the mobile elements to susceptibility to schizophrenia. Thus, it
is possible to state that Alu insertion sites may be useful in detecting risk
genes associated with schizophrenia.
P-14-13
Single photon emission-computed tomography (spect)
study: Evidence for left hemispheric dysfunction in schizophrenia
Nikolina Jovanovic
Zagreb University Hospital, Department of Psychiatry, Croatia
Vesna Medved, Ivica Sain, Sunana Divosevic
Introduction: Studies conducted over the past fifteen years reported significant clinical differences between the conventional antipsychotics and
risperidone (1,2). Therefore it is relevant to examine whether the regional
cerebral blood flow (rCBF) patterns differ between the two classes of
antipsychotics. Study was performed to identify brain regions showing
changes in rCBF due to switching from conventional antipsychotic to
risperidone. We also explored how these rCBF patterns are related to the
schizophrenic symptoms.
Method: We studied twenty DSM-IV schizophrenic patients; mean age
was 35,3 (SD 9.3), mean age at onset of illness 26.8 (SD 7.6), mean duration of the illness 8,3 (SD 4,8). All were examined by technetium-99m
hexamethyl-propyleneamine oxime (HMPAO) resting brain SPECT scans
with 32 regions of interest (ROI) identified. Psychopathology was evaluated according to the PANSS, while the Simpson-Angus scale for
Parkinsonism, the Barnes-Akathisia scale and the Abnormal Involuntary
Movement Scale were used for detecting extra-pyramidal side-effects. All
assessments were performed at baseline and three months after the
switch to risperidone.
Results: Risperidone treatment was associated with significant improvement of psychopathology and movement side-effects. We found significant interhemisheric rCBF differences with left-side deficits in several
ROIs, such as gyrus frontalis medialis, central region, inferior parietalis,
superior temporalis and superior parietalis. All left-sided deficits remained
unaffected by switching to risperidone. No other rCBF differences were
found. With risperidone, total PANSS correlated negatively with right
superior temporalis (r=-0.56, p=0.011), inferior temporalis (r=-0.57,
p=0.008) and left inferior temporalis (r=-0.052, p=0.019).
Conclusion: Despite the clinical improvement seen in our patients, we
failed to show that risperidone produced any significant changes in cortical rCBF after the three months treatment. Our findings add some evidence to the previous reports of predominant left hemisphere abnormalities in schizophrenia and indicate possible associations between temporal regions perfusion and symptom severity (3).
References: (1)Harvey PD, Green MF, McGurk SR, Meltzer HY. Changes
in cognitive funcioning with risperidone and olanzapine tretament: a
large-scale, double-blind, randomized study. Psychopharmachology
2003;169: 404-11 (2) Meltzer HY, McGurk SR. The effects of clozapine,
risperidone, and olanzapine on cognitive function in schizophrenia.
Schizophr. Bull.1999; 25: 233-55 (3)Russel JM, Early TS, Patterson JC,
Martin JL, Villanueva-Meyer J, McGee MD.et al. Temporal lobe perfusion
asymmetries in schizophrenia. J Nucl Med. 1997;38:607-12.
151
P-14-14
Characterisation of schizophrenia patients in Portugal:
Results from the baseline assessment of SOHO observational study
Mariana Guerreiro Anastacio
Lilly Portugal - Produtos Farm, Alges, Portugal
Angelina Pereira, Amalia Silva, Antonio Marieiro, Jorge Humberto, Joo
Marques-Teixeira
Introduction: Schizophrenia has been under increased scrutiny over the
past years and its treatment has advanced considerably in the past
20 years. However there is some need to know how treatments are being
prescribed and how these work in actual practice. Schizophrenia
Outpatient Health Outcomes (SOHO) study was designed to address this
need by providing essential data in these issues. The primary objective of
the study is to understand the comparative outcomes and costs associated
with antipsychotic medication therapies initiated or changed during outpatient treatment for schizophrenia. The objective of this paper is to
describe the baseline characteristics of the cohort of Portuguese patients
included in the SOHO study.
Method: Non-interventional, prospective, outpatient observational study
of the treatment of schizophrenia in 10 European countries including
Portugal. Patients initiating or changing antipsychotic medication for the
treatment of schizophrenia, presenting within the normal course of care
in an outpatient setting, had at least 18 years of age, and that were non
participating in any other interventional study were included. Patients was
to be followed for a period of 3 years.
Results: A total of 30 Portuguese physiatrists participated in the study
and enrolled 160 eligible patients. Mean age was 36.5 and 65.6% were
males. There was a high prevalence of housing dependency and unemployment. Treatment cohorts were similar in almost all characteristics.
Patients being prescribed with typicals had a more favourable work status, and appeared to have a better health state rather than the remaining
cohorts. Notwithstanding, past history of substance abuse was also more
likely in this cohort. Olanzapine showed a trend of being prescribed to
patients with a less frequent history of inpatient admissions.
Conclusion: Outpatients with schizophrenia included in this study were
mainly young, male, with a decade of ongoing treated disease, slightly
over weighted, non-victimized, and predominantly dependent on their
families.
P-14-15
Haplotype analysis of polymorphisms of heat shock protein 70 gene on chromosome 6p21.3 in schizophrenia
Jung Jin Kim
Kangnam St.Marys Hospital, Psychiatry, Seoul, Republic of Korea
Chi Un Pae, Hyun Kook Lim, Oh Joo Kwon, Chang Uk Lee, Chul Lee, In
Ho Paik, Tae Youn Jun
Introduction: Heat shock proteins (HSPs) are a promising candidate gene
in schizophrenia as they are believed to play a protective role in the central nervous system. An alteration in the antibodies to the HSPs in schizophrenia patients as well as an association between the three polymorphisms of HSP70-1 (HSPA1A), HSP70-hom (HSPA1L) and HSP70-2
(HSPA1B) and schizophrenia has been reported. Therefore, this study
aimed to investigate the association between 5 SNPs (rs2227956,
rs2075799, rs1043618, rs562047, rs539689) of HSP70 gene on chromosome 6p21.3 and schizophrenia.
Method: Two hundred and ninety four patients with schizophrenia and
287 controls were enrolled in the study. Genotypings of 5 SNPs of HSP70
were performed using pyrosequencing. Tests for associations using and
multi-marker haplotypes were performed using COCAPHASE v2.403.
Single locus allele tests were also performed. Association of SNP markers
and clinical variables were analyzed by repeated measures of ANOVA.
Results: Genotypes of rs2227956 (p=0.28), rs1043618 (p=0.88),
rs562047 (p=0.47) and rs539689 (p=0.32) were not associated with
schizophrenia, but the rare rs2075799*A allele (Chi-sq=8.03 d.f.=1
p=0.0046) showed strong association with schizophrenia. Haplotypes
were significantly associated with schizophrenia (global-stat=48.11
d.f.=12 p=0.000003); the rare T-A-C-C-G haplotype showed the higher
OR for schizophrenia. Sliding windows analysis revealed a major contribu-
152
tion from rs2227956 and rs2075799 (global-stat=9.79 d.f.=2 p=0.0075),

with T-A haplotype significantly associated with schizophrenia. There was
no evidence of an association between the clinical variables and schizophrenia across the genotypes.
Conclusion: These results suggest that SNP and related haplotypes of
rs2075799 might be associated with the pathogenesis of schizophrenia.
Further studies from different study groups should be performed to confirm these results.
References: Bates PR, Hawkins A, Mahadik SP, McGrath JJ. Heat stress
lipids and schizophrenia. Prostaglandins Leukot. Essent. Fatty Acids 1996;
55: 101-107. Kim JJ, Lee SJ, Toh KY, Lee CU, Lee C, Paik IH. Identification
of antibodies to heat shock proteins 90 kDa and 70 kDa in patients with
schizophrenia. Schizophr Res 2001; 52: 127?135. Pae CU, Kim TS, Kwon
OJ, Artioli P, Serretti A, Lee CU, Lee SJ, Lee C, Paik IH, Kim JJ.
Polymorphisms of heat shock protein 70 gene (HSPA1A, HSPA1B and
HSPA1L) and schizophrenia. Neurosci Res 2005; 53(1): 8-13.
P-14-16
Impaired glicoregulation in patients with schizophrenia
before any second-generation antipsychotic treatment
Nadja Maric
Institute of Psychiatry, Belgrade, Serbia and Montenegro
Mirjana Doknic, Aleksandar Damjanovic, Sandra Pekic, Miroslava Jasovic
Gasic, Vera Popovic
Introduction: Several risk factors have been associated with diabetes
mellitus (DM) in patients with schizophrenia: positive family history of
DM, lifestyle, smoking, dietary habits, physical inactivity and antipsychotic
medication. In the present literature, most publications are focused on the
second generation antipsychotic (SGA) influence on glicoregulation.
However, less attention has been paid on abnormality in glicoregulation
in drug naive or FGA (first generation antipsychotic) treated patient with
schizophrenia. Present study has evaluated glicoregulation in FGA treated
schizophrenia patients in comparison to matched healthy controls.
Method: The cross-sectional study included 30 patients with schizophrenia
(ICD X)(FGA treated) and 27 healthy controls with neither group differences in sex distribution and age, nor in BMI. Sociodemography and illness-related variables are shown on table 1. The glucose levels, insulin levels and growth hormone levels during OGTT (oral glucose tolerance test)
were measured, together with insulin resistance index (HOMA).
Results: Fasting glucose levels did not differ significantly between
groups, but OGTT glucose peak and area under curve (AUC) were
impaired in patients in comparison to healthy controls (8.0+/-0.4 and
7.0+/-0.4 mmol/l, respectively, p=0.04; AUC: 734+/-27 and 64+/-28
mmol/l/120min, respectively, p=0.01). The borderline significance
(p=0.05, both) was found in fasting insulin levels (9.3+/-1.2 in patients
and 11.1+/-1.0 mU/l in healthy controls) and HOMA index (1.9+/-0.3 in
patients and 2.3+/-0.2 in controls). Peak OGTT insulin levels and OGTT
AUC of insulin had only a trend toward increase in schizophrenia group.
No difference was found in fasting growth hormone (GH) levels and
OGTT GH levels.
Conclusion: In comparison to healthy controls, patients with schizophrenia have an impaired glicoregulation before any SGA treatment.
Therefore, schizophrenia patients should be considered as a population
under the increased risk of glicoregulation impairment if exposed to SGA.
P-26
Psychotic Disorders V
P-26-03
Costs caused by schizophrenia illness during a five-yearperiod
Eva Lindstrm
Uppsala University, Dept. Neuroscience-Psychiatry, Sweden
Jonas Eberhard, Martin Neovius, Sten Levander
P-26-01
Unealthy life-styles in people with schizophrenia.
A preliminary literature analysis
Sonia Santelia
ASL Salerno 1. Italy, Department of Mental Health, Nocera Inferiore,
Italy
Introduction: Schizophrenia has been described as a life-shortening disease, and physical comorbidity accounts for 60% of premature deaths
not related to suicide.1 Unhealthy life styles, and exposure to psychotropic
gents associated with increased risks of metabolic complications as well,
may certainly contribute in reducing the life-expectance of such
patients.2,3 Aim of the study. A literature analysis focused to investigate
the prevalence of unhealthy lifestyles in schizophrenic population.
Method: Computerized search via MEDLINE/Pubmed databases (19802006).
Results: See Table 1. Prevalence of unhealthy life-styles in patients with
schizophrenia. Typology of unhealthy life-styles (a) Prevalence in schizophrenic patients (%) (b) Prevalence ingeneral healthy population (%)
Smoking (75-92)a (30)b Reduced physical activity (41)a (60)b Street drug
abuse (40-60)a (36)b Alcohol (33)a (14)b Unsafe sex (37- 58)a (20-48)b
Conclusion: Despite an high prevalence of unhealthy life styles in
patients with schizophrenic disorders, specific interventions finalised in
ameliorating this specific outcome are largely neglected in clinical practice. This preliminary literature analysis conversely demonstrates the need
of implementing psychosocial programs strictly focused to facilitate
healthy life changes.4
References: References 1. Lambert TJR, Velakoulis D, Pantelis C. Medical
comorbidity in schizophrenia. MJA 2003; 178: S67-S70. 2. Gentile S.
Long-term atypical treatment with atypical antipsychotics and the risk of
weight gain. A literature analysis. Drug Saf 2006; 28 (4): 303-19.
3. McCreadie RG; Scottish Schizophrenia Lifestyle Group. Diet, smoking
and cardiovascular risk in people with schizophrenia: descriptive study. Br
J Psychiatry 2003: 183: 534-9. 4. Menza M., Vreeland B, Misky S, et al.
Managing atypical antipsychotic-associated weight gain: 12-month data on
a multimodal weight control program. J Clin Psychiatry 2004; 65. 471-7.
P-26-02
Sertindole: A newly available atypical antipsychotic with
placebo level EPS
Eva Lindstrm
Jonas Eberhard, Agneta Bjrck Linne
Introduction: Sertindole is an antipsychotic agent that shows affinity for
D2, 5-HT2A, 5-HT2C, and 1-adrenoceptors. Preclinical research suggests
that sertindole has a preferential effect on the activity of limbic and cortical dopaminergic neurons, and clinical trials have confirmed that sertindole is efficacious at a low D2 receptor occupancy, comparable to that
produced by clozapine, which may confer a lower risk of EPS.
Method: PubMED was searched for all randomised controlled trials of
sertindole where EPS ratings were performed and published in English
language in peer-reviewed medical journals. All of these published studies
were reviewed regarding the occurrence of EPS in patients.
Results: Five clinical trials of sertindole fulfilled these criteria.
Comparators were placebo, haloperidol and risperidone. Rating scales
used were: Simpson -Angus Scale (SAS), Barnes Akathisia Scale (BAS),
and Abnormal Involuntary Movement Scale (AIMS). Furthermore, the
need for anti EPS medication, and the incidence of EPS-related events
(presented as percentage of patients), if registered, was recorded. If significant differences were reported, NNT (number needed to treat) values
were calculated and presented with point estimates and 95 % CI. In three
studies significant differences between sertindole and haloperidol were
observed. In the two remaining studies, no significant differences were
noted between sertindole vs placebo and risperidone, respectively.
Conclusion: In summary sertindole has been shown to have an exceptionally low propensity for EPS, and abnormal movement side effects.
Introduction: The early onset and chronic nature of schizophrenia result

in major cumulative direct costs from medication, hospitalization and
sheltered living, but also large indirect costs due to inability to participate
fully in the work force.
Method: To explore the direct and indirect costs we followed a cohort of
158 risperidone-treated patients with schizophrenia, and schizophreniarelated disorder, annually over five years. The study describes costs for
medication, hospitalization, sheltered living, and productivity losses, as
well as degree of social isolation.
Results: The direct costs were dominated by hospitalization and sheltered
living expenses, while drug costs only represented 6% of the direct costs.
Indirect costs represented 43% of the total costs during the five years.
About 12% worked full-time, and 12% worked part-time, resulting in
large productivity losses.
Conclusion: As a consequence of the national mental healthcare reform,
a dramatic shift of costs from hospitalizations to sheltered living took
place, and a high degree of social isolation was seen, with about 20%
completely without social contacts and about 30% seeing friends less
often than once a week.
P-26-04
Five years follow up during antipsychotic treatment;
efficacy, safety, functional and social outcome
Eva Lindstrm
Jonas Eberhard, Sten Levander
Introduction: Explore the long-term course of schizophrenia and related
disorders.
Method: Naturalistic examination of 158 patients initially treated with
risperidone (mono-therapy or in combination with other psychotropic
drugs) over 5 years.
Results: Stable symptomatology and side effects. Clinician GAF scores
were 51-60, but patients self-ratings were higher. Clinician and patient
CGI scores were at the same level. Annual inpatient days decreased but
days in sheltered accomodations increased still more. Only 12% of the
patients studied or worked full-time. One in four had no social contacts
except with staff. Eight patients died during the five years.
Conclusion: The findings underline the chronicity and seriousness of psychotic disorders in terms of social outcome and, indirectly, the low quality
of lifeof this group of persons. Patients were generally well aware of their
illness and able to sort out symptoms from drug side effects. This opens
for more active involvement of patients in monitoring their own treatment.
P-26-05
The precise time of prenatal infection predicts symptom
subtypes in an animal model of schizophrenia
Joram Feldon
Swiss Federal Institute, Behavioural Neurobiology, Schwerzenbach,
Switzerland
Benjamin K. Yee, Urs Meyer
Introduction: Maternal infections during pregnancy increase the incidence of neuropsychiatric disorders with a presumed neurodevelopmental
origin in the offspring, including schizophrenia and autism. However, this
association appears to be critically dependent on the precise times of the
prenatal infectious events. In particular, the long-term functional consequences of prenatal immune activation at different times of gestation
may be related to differing symptom clusters of schizophrenia.
153
Method: In order to study the temporal dependency in an animal model

of prenatal viral-like infection in mice, we administered pregnant dams on
gestation day (GD) 9 or GD17 with the viral mimic polyriboinosinic-polyribocytidilic acid (PolyI:C; 5mg/kg, i.v.) or vehicle solution. The resulting
adult offspring were then tested in a number of behavioral and pharmacological paradigms relevant to the positive-negative dichotomy and cognitive symptoms of schizophrenia.
Results: Here, we show that whilst deficits in prepulse inhibition (PPI)
exclusively emerges after prenatal immune activation on GD9, prenatal
immune challenge on GD17 specifically leads to working memory impairments in the Morris water maze. In addition, a potentiation of the locomotor reaction to the NMDA-receptor antagonist dizocilpine (MK-801;
0.15 mg/kg; i.p.) only appears after prenatal PolyI:C exposure in late but
not middle gestation, whereas enhanced locomotor responding to systemic administration with the dopamine-receptor antagonist amphetamine (AMPH; 2.5 mg/kg; i.p.) emerges independent of the precise timing
of the prenatal immunological manipulation.
Conclusion: Our findings here and in previous reports (Brain Behav.
Immun. 20:378-388, 2006; J. Neurosci. 26:4752-4762, 2006) thus indicate that prenatal immune activation in early/mid pregnancy leads to a
variety of abnormalities associated with positive symptoms of schizophrenia,
whereas prenatal immune activation in late gestation results in the emergence of behavioral and pharmacological dysfunctions particularly associated with negative and cognitive symptoms of this disorder.
References: Brain Behav. Immun. 20:378-388, 2006; J. Neurosci.
26:4752-4762, 2006
P-26-06
Searching endophenotype in schizophrenia: Comparison of
metabolite level in the frontal lobe in H1 MRS among
patients, healthy siblings and control group
Hanna Karakula
Medical University of Lublin, Department of Psychiatry, Poland
Elzbieta Sokolska, Elzbieta Szmycinska, Barbara Bobek - Billewicz, Anna
Grzywa, Katarzyna Szajer, Justyna Pawezka, Kinga Szymona, Rafal
Piszczek
Introduction: Due to the lack of clear-cut test detecting schizophrenia,
features which could differentiate a group of patients with schizophrenia,
their healthy relatives, and healthy population are being sought, being at
the same time external expression of genes responsible for causing the illness (endophenotypes). Aim: The aim of the work was to seek endophenotype markers in schizophrenia in various parts of the frontal lobe of the
CNS through comparing the level of metabolites in H1 MRS among the
group of schizophrenics, their healthy siblings and control group.
Method: A group of 84 persons: 32 schizophrenics, their 34 healthy siblings, 18 controls were examined. The average age among patients, their
siblings and control group are respectively: 26,7, 25,8 and 28,5. Each person
had the brain examined with MRI and H1 MRS methods (Chemical Shift
Imaging voksel 10x10x10 mm). Both right (R) and left (L) hemisphere of
the brain were examined and the examination included NAA, CHO, CR
measurements in the following structures of the frontal lobes: nucleus
caudatus (1), lenticular nucleus (2), lateral nucleus (3), prefrontal cortex
(4), anterior cingulate gyrus (5), centrum semiovale (6), posterior cingulate gyrus (7).
Conclusion: 1. No important statistic differences were achieved in the
measurements of the examined metabolites referring to structures: 1 R
and L, 2 R and L, 3 R and L, 4 R, 5 L, 7L. 2. Structures, in which differences between the examined groups are of greatest statistic importance
refer to at least two metabolites, are: left prefrontal cortex (TE = 135ms),
right part of anterior cingulate gyrus (TE = 135 ms), left part of centrum
semiovale (TE = 30 ms). 3. The IV and V endophenotype criteria are satisfied for these areas. The research has been done thanks to the grant of
KBN 3PO5B03024.
154
P-26-07
Searching for endophenotype in schizophrenia:
Importance of visual-spatial working memory
Hanna Karakula
Medical University of Lublin, Department of Psychiatry, Poland
Josef Parnas, Anna Grzywa, Justyna Pawezka, Katarzyna Szajer, Aneta
Opolska, Anna Urbanska, Rafal Piszczek
Introduction: Disturbances of cognitive function (cognitive impairment)
have very important position among many pretenders to be called
endophenotype in schizophrenia and among them particularly disturbance of visual-spatial working memory. The aim of this study was confirmation IV and V criteria for endophenotype according to Gershon and
Goldin (1986) in relation to visual-spatial working memory, and indication, out of tests measuring it, the most sensitive instrument allowing
(enable) further studies using endophenotypes.
Method: 47 patients with schizophrenia according to ICD-10 and DSM-IV,
47 of their healthly siblings and 47 control subjects were involved. Tests
connected with measurement of visual-spatial working memory were performed: WCST, TMT-B, Dot- test, Tower of Hanoi.
Results: Statistcally significant differences were noted between: group
of patients and control: Dot Test, Tower of Hanoi (N3), WCST (TA, %E,
%PR, %PE, %NE, %CLR, CC, TCFS, FMS) group of patients and siblings:
Dot Test, Tower of Hanoi (N3), WCST (TA, %E, %PR, %PE, %NE, %CLR,
CC, TCFS, FMS) group of healthly siblings and control: only towards two
tests: TMT B, WCST (%TE, % PE, %PR, CLP)
Conclusion: In accordance with conception of endophenotypes pretenders to be called endophenotype in schizophrenia are visual-spatial
working memory, but only two tests: TMT B and WCST seem to be useful in further studies.
P-26-08
Antipsychotics and sexual self-perception in schizophrenic
patients
Marija Vucic Peitl
KBC Rijeka, Psychiatric Clinic, Croatia
Djulijano Ljubicic, Vjekoslav Peitl
Introduction: The goal of this research was to determine if there is a difference in sexual self-perception (in the seven aspects of sexual self-perception) among acute and chronic schizophrenic patients, regarding the
type of antipsychotic medication.
Method: Two groups of schizophrenic patients were analyzed (100 acute
and 100 chronic patients), treated in the psychiatric clinic of KBC Rijeka,
in 1998 and 1999, regarding the type of antipsychotic medication (typical and atypical antipsychotics), and their influence on the seven aspects
of sexual self-perception (sexual self-scheme, sexual consciousness, sexual readiness, sexual adventurism, negative emotionality, sexual non-competence, sexual satisfaction).
Results: Results of this research show that typical antipsychotics, in acute
and chronic schizophrenic patients, have no effect on the aspects of sexual self-perception, while atypical antipsychotics (in this research that
mostly refers to clozapine), in chronic schizophrenic patients, have positive effect on the aspects of sexual self-scheme and sexual adventurism.
Therefore, patients who used clozapine achieve better results on aforementioned scales. Results also show that side effects of typical and atypical antipsychotics have no effect on the aspects of sexual self-perception.
Conclusion: Atypical antipsychotics, especially clozapine, contribute to a
longer, better remission and better cognitive functioning in chronic
schizophrenic patients, which allows better expression of sexual selfscheme and greater need for sexual adventurism. Side effects of antipsychotics have no effect on the sexual self-perception, which confirms the
complex definition of self-perception as a core of human being.
P-26-09
Association between RGS4 genetic variants and schizophrenia: A structured case-control and family analysis in a
Chilean sample
Aida Ruiz
Robin M. Murray, John Powell, Eduardo Miranda, Carlos Encina, Mario
Quijada, Pak Sham
Introduction: Recent analyses have reported that polymorphisms in the
RGS4 gene, on 1q21-22, are associated with schizophrenia. This study
analysed this possible association in an admixed sample, ethnically different from populations examined in previous reports.
Method: The study was carried out in a case-control sample composed
of 112 cases with DSM-IV schizophrenia, and 240 unaffected control subjects; and a sample of 44 DSM-IV schizophrenics families, recruited in
Santiago, Chile. Four RGS4 markers, previously associated with schizophrenia, and 10 ancestry-informative markers were genotyped. The data
were analysed by means of the UNPHASED program. Intermarker linkage
disequilibrium (LD), single marker and haplotype associations were evaluated using the Pedigree Disequilibrium Test (PDT) and COCAPHASE.
Analysis of population stratification, in the case-control sample, was carried out using L-POP software. The structured association analysis was
performed with WHAP program.
Results: The analysis of population structure detected stratification in the
case-control sample; however the cases and controls were well matched.
All markers were in Hardy-Weinberg equilibrium. Significant LD was
observed for all pairwise calculations. In both samples, none of the SNPs
included in this analysis were found to be associated with illness
(P >0.05), and no significant haplotypic association was observed
(P > 0.05). The structured association analysis did not show confounding
effects of population stratification.
Conclusion: No evidence was found to support an association between
genetic variants in the RGS4 gene and schizophrenia in this sample; even
though the genetic analysis suggested that the Chilean sample showed
similarities with ethnically different samples, previously described as having association with this gene. Among other explanations, these results
might be the consequence of inadequate statistical power.
References: Kodavali V. Chowdari KV, Mirnics K, Semwal, WoodJ,
Lawrence E, Bhatia T, Deshpande SN,Thelma B.K, Ferrell RE, Middleton
FA, Devlin B, Levitt P, Lewis DA, Nimgaonkar VL. Association and linkage
analyses of RGS4 polymorphisms in schizophrenia. Hum Mol Genet.
2002; 1:11373-1380. Michael E. Talkowski ME, K. V. Chowdari KV, Lewis
DA, Nimgaonkar1 VL.Can RGS4 Polymorphisms Be Viewed as Credible
Risk Factors for Schizophrenia? A Critical Review of the Evidence.
Schizophr Bull. 2006; 32: 203-208.
P-26-10
DTNBP1 gene and schizophrenia: Family-based and structured case-control association study in an admixed population in Chile
Aida Ruiz
Pak Sham, John Powell, Eduardo Miranda, Carlos Encina, Mario Quijada,
Robin M Murray
Introduction: Evidence for association between schizophrenia and
genetic variants in the DTNBP1 gene located on 6p22.3 has been recently
described. The aim of this study was to conduct an association analysis
between schizophrenia and the DTNBP1 gene in a Chilean admixed sample.
Method: Forty-four families affected by schizophrenia; and a case-control sample composed of 112 schizophrenic patients, and 240 unaffected
control individuals, were collected in Santiago, Chile. Diagnosis was made
according to DSM-IV criteria. Ten DTNBP1 SNPs reported to be associated
with schizophrenia, and ten ancestry-informative markers were selected
for genotyping. Inter-marker linkage disequilibrium (LD) was measured
using UNPHASED program. The Pedigree Disequilibrium Test (PDT) and
the COCAPHASE program were used to analyse single marker and haplotype associations. A population structure analysis was performed using
the L-POP program, to detect hidden population stratification in the casecontrol sample. The WHAP program was used to carry out the structured
association analysis.
Results: Even though the analysis of population structure found evidence

for population stratification, the cases and controls were well matched. In
both samples, no deviation from the Hardy-Weinberg equilibrium was
found and significant LD was observed for most pairwise calculations. No
single marker achieved a significant allelic association (p<0.05), and tests
for haplotype analysis showed no association (p<0.05). Structured association analysis of DTNBP1 gene did not detect possible spurious findings
in the case-control sample.
Conclusion: In comparison with previous studies in ethnically diverse
samples, the Chilean samples showed a similar pattern of allele frequencies, LD patterns, and haplotype frequencies. However, association
between DTNBP1 gene and schizophrenia was not confirmed. Potential
methodological limitations of association studies could explain these
results.
References: Straub RE, Jiang Y. Charles J. MacLean CJ, Ma Y, Webb BT,
Myakishev MV, Harris-Kerr C, Wormley B, Sadek H, Kadambi B, Cesare
AJ, Gibberman A, Wang Xu, ONeill FA, Walsh D, Kendler KS. Genetic
Variation in the 6p22.3 Gene DTNBP1, the Human Ortholog of the Mouse
Dysbindin Gene, Is Associated with Schizophrenia. Am. J. Hum. Genet.
2002; 71:337-348. Williams NM, ODonovan MC, Owen MJ. Is the
Dysbindin Gene (DTNBP1) a Susceptibility Gene for Schizophrenia?
Schizophr Bull 2005; 31: 800-805.
P-26-11
Genes for bipolar disorders and schizophrenia?: Potential
advantageous of Latin-American admixed populations for
genetic analysis
Aida Ruiz
Robin M Murray, Pak Sham, John Powell, Sonia Medina, Paul Vhringer,
Carola Espinosa, Fabiola Leiva, Ricardo Garcia, Eduardo Miranda, Jorge
Cabrera
Introduction: Recent studies have shown increasing evidence for an
overlap in genetic susceptibility for bipolar disorders and schizophrenia,
including associations of both disorders with DAOA(G72), DTNBP1,
COMT, BDNF, DISC1, and NRG1. Susceptibility alleles for neuropsychiatric
disorders, and patterns of linkage disequilibrium, are likely to differ in ethnically different populations. Furthermore, admixture between genetically
different populations may produce admixture disequilibrium. Thus LatinAmerican admixed populations offer an opportunity to evaluate the role
of genetic factors in the aetiology of complex disorders, and the possible
genetic overlap between schizophrenia and bipolar disorders. The paper
reviews candidate gene studies on schizophrenia and bipolar disorders in
Latin-American samples.
Method: All citations in Medline up to October 2006, and recent conference reports were collected. Family and case-control studies of candidate
genes in bipolar disorders and schizophrenia were included. Statistical
package SPSS v.12.0 was used for descriptive data analysis.
Results: A total of 25 studies, including case-control or/and family
designs, were found. Twenty-four candidate genes were examined in
schizophrenia and/or bipolar samples, obtained from five populations:
Brazilian, Chilean, Colombian, Costa Rican, and Hispanic USA. Diverse
and discrepant association results were reported. Ancestry-informative
markers for controlling population stratification, and structured association analysis, were used only in the Chilean case-control samples.
Conclusion: Methodological limitations, associated with inadequate statistical power and insufficient control for population stratification, among
others, might be an important source of inconsistent results. Structured
association methods should be considered in case-control studies of
admixed populations.
References: Maier W, Hfgen B, Zobel A, Rietschel M. Genetic models of
schizophrenia and bipolar disorder. Overlapping inheritance or discrete
genotypes? Eur Arch Psychiatry Clin Neurosci. 2005; 255: 159-166
Craddock N, ODonovan MC, Owen MJ. The genetics of schizophrenia and
bipolar disorder: dissecting psychosis. J Med Genet. 2005; 42:193-204.
155
P-26-12
Mismatch negativity in the visual modality is reduced
among patients with schizophrenia
Jan Libiger
Charles Univ Medical School, Dept.of Psychiatry, Hradec Kralove, Czech
Republic
Ales Urban, Jan Kremlacek, Jiri Masopust, Miroslav Kuba
Introduction: Mismatch negativity ( MMN) is a negative deflection of
amplitude in the course of event related potentials (ERPs) that is elicited
by a deviant stimulus in a repetitive sequence of standard stimuli. MMN
in the auditory modality has been investigated as an index of preattentional information processing in schizophrenia The existence of MMN in
the visual modality has been considered controversial. However, a significant deflection of ERP elicited by a deviant visual motion stimulus in a
sequence of standard stimuli was reported in healthy volunteers in the
interval 140-260 ms.
Method: We investigated the ERPs to visual motion stimuli in a group of
25 patients (18 men and 7 women) and a matched group of healthy controls. The median age of patients was 25 years. ERPs to circular visual
stimuli that differed in the direction of motion were recorded in a neurophysiological laboratory. The differences in area under curve (AUC)
between responses to standard stimuli and deviant stimuli were computed.
Results: In the Ol and Fz electrodes significant reductions (T-test,p=
0,027;p=0.037) were found between the summed ERP responses to
deviant stimuli in the group of patients and matched controls in the interval 120-240 ms. We have also found an association between global
assessment of functioning (GAF) score in patients and the size of MMN
reduction at the left occipital electrode.
Conclusion: These findings support the hypothesis that a disturbance of
early ( preattentive) cognitive processes among patients with schizophrenia
is present also in the visual modality, which may be indicative of a dysfunction of magnocellular visual system in schizophrenia.
References: 1. Umbricht D,Krljes S, Mismatch negativity in schizophrenia: a meta analysis, Schizophrenia Res 2005;76:1-23 2. Pazo-Alvarez P,
Cadaveira F, Amenedo E, MMN in visual modality: a review, Biological
Psychology 2003;63:199-236 3.KremlacekJ, Kuba M, Kubova Z,Langrova
J, Visual mismatch negativity elicited by magnocellular system activation,
Vision Res. 2006;46:485-490
P-26-14
Comparative research of efficacy of laser therapy in combination with psychopharmacotherapy in treatment of endogenic psychosis
Marat Assimov
Kazakh National Medical Univ., Dept. of Psychiatry, Almaty, Kazakhstan
Introduction: Psychiatry been medical discipline should not refuse other
methods of treatment such as nonmedicamental. Especially modern medicines are not ideal.
Method: We researched the efficacy of abovevenous (AVLT) and intravenous laser therapy (IVLT) of patients, whose getting psychopharmacotherapy (PPT) for 6 weeks was not effective enough. Registration of
symptoms was realized with the helping of CGI, HAM-D and BPRS.
Examined group of patients consisted of 50 people in the age of 35,2
1,3. Among them were 35 men (70%) and 15 women (30.0%) (according to ISD 10): F20.0 - 13 people (26.0%), F25 - 17 people (34.0%), F31 8 people (16.0%) and F33 - 12 people (24.0%). They were divided into
two groups with the helping of random selection. One of the groups got
AVLT and PPT, the other - IVLT and PPT.
Results: IVLT is more effective than AVLT: after using AVLT according to
CGI no cases with strong therapeutic effect were noticed, medium therapeutic effect was in 28% of cases and in 42% of cases therapeutic effect
was weak; using IVLT showed 36% of cases with medium effect and 48%
with weak one. AVLT and IVLT influence differently upon depressive disorders: AVLT according to HAM- from 27,3 0,9 to 14,5 1,0; and IVLT
- from 30,5 1,0 to 15,5 1,2. Factorial analysis according to Hamilton
scale demonstrated that addition of laser therapy to psychopharmacotherapy influences differently upon affective (9% - AVLT and 11% IVLT) and somatic symptoms (11% - AVLT and 17% - IVLT). AVLT and IVLT
insignificantly reduces depressive-paranoidal and hallucinatory-paranoidal
symptoms (less than 50% of reduction) but intravenous laser therapy
influences upon depressive-paranoidal symptoms more effective than
upon hallucinatory-paranoidal ones: reduction is about 50%.
Conclusion: Laser therapy as one of the methods of nonmedicamental
therapy can be used in combination with psychopharmacotherapy taking
into consideration the leading syndrome.
P-26-13
Acupuncture and psychopharmacotherapy in treatment of
endogenic psychotic disorders
P-27
Psychotic Disorders VI
Marat Assimov
Introduction: Modern psychopharmacological drugs (psychopharmacotherapy - PPT) cause different problems: high price, side effects
(increasing of the body weight and etc). It is necessary to extend using of
nonmedicamental methods of treatment.
Method: Comparative research work of acupuncture efficacy was done:
corporal acupuncture (CA) and auricular acupuncture (AA) among
patients with low efficacy of PPT. Clinical mark of symptoms was realized
with the helping of CGI, HAM-D and BPRS. Were examined 50 patients
with following diagnoses: 12 people with F20.0, 12 people with F25, 8
people with F31 and 18 people with F33. Patients were set into two
groups with the helping of random selection. In the first group CA was
applied simultaneously with PPT, in the second group AA was applied
with PPT.
Results: Using AA showed therapeutic effect in 92% of cases (according
to CGI): 32% - strong effect and 60% - medium effect. Using CA
showed: 20% - strong therapeutic effect, 36% - medium effect. AA influences upon efficacy of antidepressants more effective than CA. Influence
of AA is more effective upon somatic ( 28%) and affective (27%) symptoms; efficacy of CA influence upon the same symptoms is less - 12%
and 13%. CA is more effective than AA (according to BPRS) in treatment
of hallucinatory-paranoidal disorders. AA is more effective, than CA in
treatment of depressive-paranoidal (more than 50% of reduction of
symptoms).
Conclusion: Differential using of various methods of acupuncture in
combination with PPT, promotes clinical improvement of patients state
suffering from endogenic mental disorders.
156
P-27-01
Cerebral morphological correlates of neurological soft
signs in first-episode schizophrenia
Pablo Toro
Germany
Philipp Thomann, Vasco dos Santos, Silke Bachmann, Frederik Giesel,
Marco Essig, Johannes Schroeder
Introduction: A subtle impairment of motor coordination functions is
frequently found in patients with manifest schizophrenia. Clinically these
deficits present as neurological soft signs (NSS).
Method: Optimized voxel-based morphometry (VBM) was used to investigate gray matter (GM) density and its putative association with NSS in
42 patients with first-episode schizophrenia and 22 healthy controls. VBM
analysis comprised (a) structural comparison of the two groups and (b)
correlation between NSS-scores and GM density.
Results: NSS scores were significantly higher in patients. In relation to
healthy comparison subjects, loss of GM density was pronounced in the
temporal lobe (both neocortical fields and substructures of the medial
temporal lobe). In patients with schizophrenia, higher rates of NSS were
related to a reduced GM density in the pre- and postcentral gyrus, the
cerebellum and in subcortical regions (caudate nucleus and thalamus).
Conclusion: This results might support the hypothesized model of a disrupted cortico-cerebellar-thalamic-cortical circuit in schizophrenia.
P-27-02
Remediation of facial affect decoding and visual scanpath
deficits in schizophrenia
Kathryn McCabe
Nisad/Uni of Newcastle, Medicine and Public Health, Australia
Carmel Loughland, Martin Cohen, Patrick Johnston, Terry Lewin, Mick
Hunter, Vaughan Carr
Introduction: People with schizophrenia are observed to have marked
deficits in their ability to identify and discriminate between various facial
expressions of emotion. These deficits are commonly interpreted as a dysfunction in the neurocognitive mechanisms that underlie face processing.
This study represents the first phase of a study examining remediation of
face emotion perception and visual scanpath deficits in patients with
schizophrenia.
Method: The sample consisted of 25 schizophrenia and 25 control subjects. Visual scanpaths were recorded while subjects viewed fourteen
faces depicting seven basic emotions (happy, sad, neutral, fear, disgust,
surprise, anger). In the information sequencing and information retention/integration tasks, another set of face images depicting the same
seven emotions were presented, overlaid by a five-by-five tile matrix. In
the sequencing task, subjects removed as few tiles as necessary for them
to identify the facial expressions. In the retention/integration task,
removed tiles were immediately replaced as each new tile was selected.
Results: The scanpath results support previous findings in schizophrenia
patients of a restricted visual scanpath strategy for viewing faces, characterised by fixations of longer duration (p<0.05) and a shorter raw scanpath length (p<0.05). Disturbances were most apparent in patients for
the angry face. In the sequencing and retention/integration tasks, the
controls and patients did not differ from each other in the overall number
of tiles removed (mean = 3 tiles). However, in the retention/integration
task patients were twice as inaccurate compared to controls (29% vs controls=11%).
Conclusion: These findings provide further evidence of visuo-cognitive
disturbances in people with schizophrenia, suggesting that patients have
a deficit in the selection and integration of salient facial information.
Remediation targeted at low level visuo-motor deficits using proprioception training may provide one viable method for improving visuo-cognitive performance and the psychosocial outcomes of people with schizophrenia.
P-27-03
Role of strategic self-regulation and executive attention in
schizophrenia
Gricel Orellana
University of Chile, Dept. of Psychiatry, Santiago, Chile
Andrea Slachevsky, Marcela Pena
Introduction: Objective: Contribute to explain the mechanisms of
behaviour disorders in schizophrenia, specifically disexecutive behaviour.
Two functions have not been completely studied in schizophrenia: executive attention and strategic self-regulation of behavior. The aim of our
study is to determine which of the three attentional networks - alert, orientation and executive attention - works abnormally in schizophrenia and
if patients present an upheaval the self-regulation. We also study the relation between troubles in these functions and the existence of psychosocial problems.
Method: 20 patients, of both sexes, aged 18 to 30 years, each with only
one psychotic episode treated. The following tests were applied: Test of
Raven to evaluate IQ; ANT to evaluate attentional networks; Mattiss
Dementia Rating Scale, WCST and FAB to evaluate executive functions
and Six Element Test to evaluate strategic self-regulation. The disexecutive
behaviour was evaluated the DEX and the Grefexs questionnaires. In
order to evaluate squizophrenia symptoms, we applied PANSS. A group
of healthy controls matched by sex, age and educational level was included
in the study.
Results: Our results revealed that patients presented a disorder of the
three attentional networks, especially the executive attention, and poor
performances in the Six Elements tests - they applied non efficient strategies during the execution of the task. These deficits are not correlated
with the disexecutive behaviours. Moreover, patients presented statistical
differences with controls in Raven, WCST, Mattis s Dementia Rating Scale

and disexecutive questionnaires.
Conclusion: Our results suggest that troubles in executive attention and
strategic auto-regulation could explain some patological behaviours in
schizophrenia.
References: (1) Fan J., McCandliss B., Sommer T., Raz A. & Posner M. I.
Testing the Efficiency and Independence of Attentional Networks. Journal
of Cognitive Neuroscience 14, 340-347 (2002). (2) Shallice T., & Burgess
P. Frontal deficits in strategy application following lobe damage in man.
Brain 114, 727-741 (1991). (3) Slachevsky A, Prez C, Silva J, Orellana G,
Preafeta M, Alegria P, Pea M. Crtex prefrontal y trastornos del comportamiento: Modelos explicativos y mtodos de evaluacin. Rev.
Chilena de Neuropsiquiatra 43:2:77-170 (2005). Grant: Fondecyt
1050175
P-27-04
Characteristics of emotional related cognitive function in
schizophrenia evaluating exploratory eye movements, and
fMRI: Comparison with healthy subjects
Yoshihisa Shoji
Cognitive and Molecular Resear, Neuropsychiatry, Kurume, Japan
Kiichiro Morita, Toshimasa Matsuoka, Hiroko Yamamoto, Hiroyasu Igimi,
Masayuki Inoue
Introduction: In this study, we analyzed the exploratory eye movements
to evaluate the effects of an emotion in facial cognition between schizophrenic patients and healthy controls, and also performed fMRI study.
Method: Twelve schizophrenic patients diagnosed by ICD-10 (10
Paranoid and 2 non-paranoid) and age-sex matched 12 healthy subjects
participated in this study. Eye movements were recorded while subjects
viewed the baby photograph(smiling or crying) by using an eye-mark
recorder (nac, EMR-8, Tokyo, Japan). Total eye scanning length (TESL) and
total number of gaze points (TNGP) were analyzed for data. To measure
activation of brain region, 1.5T MRI (SEIMENS, MAGNETON SYMPHONY,
germany) was used. Smiling or crying baby photographs were presented
with adapted voices. Ethics Committee of Kurume University approved
the present study. Written informed consent was obtained from all subjects prior to study.
Results: Using the exploratory eye movements, the TESL for controls was
significantly longer than for patients in both stimuli. When viewing a smiling baby was longer than that when viewing a crying for healthy subjects. However, the TESL when viewing of a smiling baby was similar to
that when viewing a crying baby for patients. The TNGP for controls was
significantly larger than for patients in both stimuli. TNGP when viewing
a smiling baby was longer than that when viewing a crying for healthy
subjects. However, the TNGP when viewing of a smiling baby was similar
to that when viewing a crying baby for patients. Activation of fMRI
around amygdala area and anterior cingulate were observed in healthy
subjects when viewing a crying baby, activation of anterior cingulate
without activation of amygdala was not activated in patients when viewing a crying baby. However, a smiling baby activated amygdala without
activation of anterior cingulated area in patients but not in controls.
Conclusion: These finding indicate that the impairment of emotional
processing are characterized in schizophrenic patients.
References: 1)Morris JS, Frith CD, Perrett DI et al (1996) A differential
neural response in the human amygdale to fearful and happy facial
expressions. Nature, 383: 812-815 2)Hironobu N, Kiichiro M, keiichiro M
et al (2003) Improvement of exploratory eye movements in schizophrenic
patients during recovery period
P-27-05
Cognitive functioning in abstinent heroin-abuser schizophrenics and in their non-abusers schizophrenic counterparts
Joao Marques-Teixeira
Oporto University, Porto, Portugal
Introduction: This report examined a broad range of cognitive functioning in a group of 20 days abstinent, heroin-abuser schizophrenic
patients (ASZ).
157
Method: Measures of attention and concentration, learning and memory,

executive functioning, processing speed, language and communication,
verbal comprehension, and perceptive organization, organized in a comprehensive neuropsychological battery (ACECF) developed in our department, were administered to 23 ASZ patients. A comparison group of nonsubstance-abusing schizophrenic patients (SZ) presenting for inpatient
psychiatric treatment and a normal controls group (C) were also examined. We hypothesized that the neurobiological impact of heroin abuse
and abstinence would cause ASZ to manifest deficits in all domains of
cognitive functioning relative both to controls and non-abusing
SZ patients.
Results: Results revealed that ASZ displayed significant memory, attention and perceptive organization impairments relative to controls, but perform better than their non-abuser SZ counterparts for all cognitive
domains except for verbal comprehension, language and communication
and perceptive organization; for these domains they have performance
levels equal to their non-abuser SZ counterparts.
Conclusion: These results are consistent with past studies that have
found cocaine-abuser SZ to manifest memory impairment (Serper et al.,
1995; 2000), but the effects of heroin on the cognitive functioning of SZ
patients remain relatively unknown. The results presented here highlight
the importance of regular and objective screening of the cognitive performance in those schizophrenic patients that abuse heroin. These results
are also discussed in terms of the clinical implications of the relative
improvement of cognitive function in schizophrenics that abuse heroin.
References: Serper MR, Alpert M, Richardson NA, Dickson S, Allen M,
Werner A: Clinical effects of recent cocaine use in acute schizophrenia.
Am J Psychiatry 152: 146469, 1995. Serper, MR, Copersino, M.,
Richarme, D., Vadhan, N. and Cancro, R: Neurocognitive functioning in
recently abstinent, cocaine-abusing schizophrenic patients. J. Substance
Abuse 11: 205-213, 2000.
P-27-06
Long-term effects of jl13, an atypical-like antipsychotic, on
rat glutamate receptors
Frank Tarazi
Harvard Medical School - McLea, Psychiatric Neuroscience, Belmont, USA
Taylor Moran-Gates, Matthew Gardner, Cedric Lamy, Amaury Graulich,
Jean-Francois Liegeois
Introduction: JL13, 5-(4-methylpiperazin-1-yl)-8-chloro-pyrido [2,3-b]
[1,5] benzoxazepine fumarate, displays clozapine-like activity in several
behavioral models predictive of antipsychotic activity or neurological side
effects (1), in spite of its weak antagonistic activity at dopamine (DA) D2
receptors as determined by in vitro binding (2) or electrophysiological
studies (3). Recently, we found that JL13 displayed an atypical-like
antipsychotic profile on DA (D1, D2, D3, D4), 5HT1A and 5HT2A receptors after chronic administration (4). In this study, we also evaluated the
long-term effects of JL13 on different glutamate receptor subtypes in rat
forebrain regions and compared previous findings to rats treated with
typical (haloperidol) or atypical (clozapine, olanzapine, risperidone and
quetiapine).
Method: Two groups (N=7) of rats received control vehicle or JL13
(10.0 mg/kg/d) by osmotic minipumps implanted subcutaneously for
4 weeks. At the end of treatment, animals were sacrificed and their brains
were processed for in vitro glutamate receptor autoradiography.
Results: Four weeks of continuous infusion of JL13 (10 mg/kg) selectively
decreased binding of [3H]MK801 to NMDA/MK-801 modulatory binding
site in medial (by 43%) and lateral (by 36%) CPu. These effects are similar to previously reported effects of other established atypical but not typical antipsychotics. In contrast, the strychine-insensitive glycine binding
site appears to be more resistant to the long-term actions of JL13 since
the drug failed to alter binding of [3H]glycine to NMDA/Glycine binding
site in all forebrain regions examined. Repeated treatment with JL 13
selectively increased AMPA receptor binding in medial (41%) and lateral
(45%) CPu, and not in other brain regions; an effect shared by other
atypical antipsychotics.
Conclusion: Atypical-like antipsychotic effects of JL13 on glutamate
receptor subtypes further support the development of this compound as
a novel atypical antipsychotic agent. Acknowledgment: Supported by
MH-068359 and NARSAD (F.I.T.). J.-F.L. is Senior Research Associate of the
158
FNRS. 1 Department of Psychiatry, Harvard Medical School, Boston MA,

USA; 2 Mailman Research Center, McLean Hospital, Belmont MA 02478,
USA; 3 University of Lige, Drug Research Center, Laboratory of Medicinal
Chemistry (B36), Lige B-4000, Belgium
References: (1) Ellenbroek & Ligeois, CNS Drug Rev 2003, 9:41 (2)
Ligeois et al, J Med Chem 1994, 37:519 (3) Seutin et al, Int J
Neuropsychopharmacol 2000, 3:S128 (4) Moran-Gates et al, J Neurosci
Res 2006, 84:675
P-27-07
Relationship of symptoms and cognitive abilities to specific
components of decisional capacity for informed consent in
patients with schizophrenia
Paola Castelli
Hospital Las Higueras, Psiquiatra, Talcahuano, Chile
Introduction: Previous studies suggest that cognitive impairment is the
strongest predictor of capacity to consent among persons with schizophrenia. Yet, few reports in this area, has been published. This study was
designed to examine the capacity of subjects with schizophrenia to provide informed consent to treatment and research participation, and to
determine the relationships among individual cognitive abilities and psychiatrics symptoms to specific components of decisional capacity.
Method: In the present study of 59 patients with schizophrenia (DSM-IV
diagnosis) aged 20 to 68 years was evaluated decisional capacity with the
MacArthur Competence Assessment Tool for Treatment (MacCAT-T), and
the MacArthur Competence Assessment Tool for Clinical Research
(MacCAT-CR). Participants were also evaluated with standardized rating
scales of psychopatology and with comprehensive neuropsychological
test battery that permitted evaluation of specific cognitive abilities.
Results: A wide range of performance was observed. The MacCAT- T and
MacCAT-CR scores were similar or worse to those previously reported in
schizophrenia. The poor performance observed on MacCAT-T was modestly related to verbal comprehension and attention abilities, but robustly
related to insight, delusions and conceptual disorganization. The poor
performance observed on MacCAT-CR was modestly related to negative
symptoms, but robustly related to education (years), verbal comprehension, perceptual organization, processing speed abilities, and executive
functioning.
Conclusion: The MacCAT-T apperead more related to symptoms than
cognitive abilities, and MacCAT-CR apperead more related to cognitive
abilities than symptoms. Investigators should be alert to the presence of
cognitive deficits, as well as negative symptoms as determinants of decisional capacity to consent to research among persons with schizophrenia.
References: 1.- Dunn LB, Palmer BW, Appelbaum PS, Saks ER, Aarons
GA, Jeste DV.Prevalence and correlates of adequate performance on a
measure of abilities related to decisional capacity: Differences among
three standards for the MacCAT-CR in patients with schizophrenia.Schizophr Res. 2006 Oct 2. 2.- Palmer BW, Jeste DV. Relationship
of individual cognitive abilities to specific components of decisional
capacity among middle-aged and older patients with schizophrenia.Schizophr Bull. 2006 Jan;32(1):98-106. 3.- Palmer BW, Dunn LB,
Appelbaum PS, Jeste DV. Correlates of treatment-related decision-making
capacity among middle-aged and older patients with schizophrenia.Arch
Gen Psychiatry. 2004 Mar;61(3):230-6.
P-27-08
In-vivo mapping of fiber pathways in schizophrenia, using
diffusion tensor MRI
Tung-Ping Su
Taipei Veterans General Hosp, Psychiatry, Taiwan
Yuan-Hwa Chou, Ya-Mei Bai, Kun-Hsien Chou, Fang-Ying Chiu
Introduction: Recent evidences in structural and functional brain imaging studies have found diverse brain abnormalities in this psychiatry disorder, suggesting that disturbances of interconnections between different
brain regions are responsible for the clinical symptoms of schizophrenia.
Diffusion tensor image (DTI) is able to noninvasively explore the organization and coherence of white matter fiber tracts, which is unique in exploring the structural and neural integrity in vivo. In this study, quantitative
index (Fractional Anisotropy, FA) derived by DTI was mapped to evaluate

the neural integrities between healthy subjects and schizophrenia
patients based on voxel-wised statistical method thought whole brain.
We hypothesized that FA of schizophrenic patients is decreased compared
with healthy groups due to disorganization and/or reduced myelin content of fiber tracts.
Method: 19 schizophrenia patients (mean age 32.78.17 y/o), who were
diagnosed and confirmed by the MINI, and 38 healthy subjects (mean age
30.39.9 y/o) were recruited for this study. Two groups were matched for
age and gender ratio. Subjects were scanned with a 1.5T Signa GE ExciteII system in TPE-VGH. All MR images were acquired within 30 minutes.
Analysis software for DTI and FA was developed on our own by C++ program. Subsequent DT-VBM was performed by SPM2 package (Wellcome
Department of Cognitive Neurology, Institute of Neurology, London, UK).
After normalization step, each normalized FA map is resliced to 1*1*1
mm3 (voxel size) and then smoothed with an 8 x 8 x 8 mm3 Gaussian kernel.
Regional differences between patient-control groups were explored
through two-tailed unpaired t-tests. In order to identify the most involved
regions, clusters containing more than 399 voxels with different of
P<0.01 were identified.
Results: We found that FA index of both side of frontal sub-Gyral WM,
right occipital lingual gyrus WM, both side of brain stem, left frontal
medial frontal gyrus and right corpus callosum in schizophrenia brain was
less than the same areas of healthy subjects.
Conclusion: The study Identified abnormal regions in schizophrenia brain
by using voxel-wise DT-MRI comparison method. Altered extrasynaptic
communication among the heterosynaptic structures was found due to
an abnormality of brain micro-circuitry and disorganization of neuronal
tracts, reflected by increased ADC values and decreased FA value, might
also reflect the pathophysiology of schizophrenia.
P-27-10
Culture and schizophrenic subtypes
Alexandra Strnad
A. Grzyzwa, H. Karakula, P. Rudalevicienne, N. Okribelashvili,
H.R. Chaudhry, E.E. Idemudia, S. Gschaider
Introduction: Aside from the International Pilot Study of Schizophrenia
(ICD-9) and the research of H.B.M. Murphy, nearly no transcultural comparative data on the frequency of schizophrenia subtypes in different cultures do exist. In an earlier paper we could show that the choice of the
classificatory system has a decisive influence on the prevalence of subtypes found (Stompe et al 2005). This paper presents the results of a
multi-center study on schizophrenia on this topic.
Method: Patients from seven countries (Austria, Georgia, Ghana,
Lithuania, Nigeria, Poland, Pakistan) with the clinical diagnoses of schizophrenia or related disorders (schizo-affective disorder, schizophreniform
disorder and brief psychotic disorder) were interviewed by SCID 1 (DSM-IV).
The final sample consisted of 1080 subjects. The frequency of schizophrenia subtypes of these patients was compared by means of chi-square
tests.
Results: Paranoid subtype was the most common in all countries (average 64.7 %), followed by schizo-affective disorder (8.6%), residual type
(7.2%), disorganized type (7.1%), catatonic type (4.7%), indifferent type
(4.7%), schizophreniform disorder (2.7%), and brief psychotic disorder
(0.3%). Only the catatonic subtype was equally distributed in all countries. The acute types (brief psychotic-, schizophreniform- and schizoaffective disorder) were overrepresented in African countries, disorganized
and residual types in Pakistan.
Conclusion: Our data confirmed the assumption that paranoid schizophrenia is, independent of culture, the most prevalent subtype in schizophrenia. The fact that the acute forms are more frequent in Africa is in
line with older studies from this region (e.g. Collomb) and with investigations on psychoses in other traditional cultures like Papua-New Guinea
(Torrey).
P-27-11
Face recognition and psychopathology in schizophrenia
Luciana Monteiro
Hospital das Clinicas - FMUSP, Psiquiatria, Sao Paulo, Brazil
Vanessa Silva, Mario Louza
Introduction: The ability to recognize faces is very important to social
interactions and is impaired in patients with schizophrenia. These deficits
appear to be stable characteristics that do not change with improvement
in clinical status. The aim of the present study is to evaluate the relationship between face recognition and psychopathology in the schizophrenia.
Method: Forty stabilized outpatients, 30 diagnosed of paranoid and
10 residual schizophrenia (DSM-IV) participated in the study, after
informed consent. Face recognition, without emotional expression, was
evaluated with Benton Test and symptoms, using the Positive and
Negative Syndrome Scale - PANSS. The performance of the sample on the
Benton Test was compared with mean levels of the general population.
Results: Schizophrenic patients had a significant worse Face Recognition
in comparison with the general population (p<0.05). The paranoid
patients showed a worse performance in the Benton test than the residual patients (p=0.023). Paranoid and residual patients had similar scores
on positive and general psychopathology of the PANSS, but residual
patients showed a higher score on negative symptoms in comparison
with paranoid patients (p=0.004). Residual patients showed a better performance on the Face recognition in comparison to paranoid patients.
Medication status showed no relationship either with the PANSS or with
the Benton Test results.
Conclusion: Even though residual patients had more negative symptoms
they had a better performance than paranoid patients on face recognition. So, face recognition deficits seem to be independent (at least partially) from the psychopathology.
References: Hall, J; Harris, J.M. 2004 Sprengelmeyer, R; Young, A.W.;
Santos, I.M.; Johnstone, E.C.; Lawrie, S.M. Social cognition and face processing in schizophrenia. British Journal of Psychiatry. 185, 169-170.
Shean, G.; Murphy, A.; Meyer, J. 2005. Social Cognition and Symptom
Dimensions. The Journal of Nervous Mental Disease. 193 (11), 751-755.
Calkins, M.; Gur, R.C.; Ragland, J.D.; Gur, R.E. 2005. Face Recognition
Memory Deficits and Visual Object Memory Performance in Patients with
Schizophrenia and Their Relatives. American Journal Psychiatry, 162(10),
1963-1966.
P-27-12
Score changes for factors in the negative symptom assessment (nsa) scale correlate with changes in functional outcome ratings
Dawn Velligan
University of Texas, Department of Psychiatry, San Antonio, USA
Scott Lancaster, Larry Alphs
Introduction: Negative symptoms of schizophrenia have been associated
with impaired functionality, and improvements in total scores on the
16-item Negative Symptom Assessment (NSA-16) scale have been shown
to correlate with improvements in functional status. The purpose of this
analysis was to determine which symptom factors within the NSA-16
structure show the strongest correlation with functional outcome measures.
Method: In 3 studies of stable outpatients with schizophrenia or
schizoaffective disorder, assessments included the NSA-16 and the following functional outcome measures: Quality of Life Scale (QLS),
Multnomah Community Ability Scale (MCAS), Global Assessment of
Functioning (GAF), Social and Occupational Functioning Assessment Scale
(SOFAS), Frontal Systems Behavioral Scale (FrSBe), Functional Needs
Assessment (FNA), and Life Skills Profile (LSP). Symptom factors in the
NSA-16 are Communication, Affect, Social Activity, Motivation, and
Motor Retardation. Changes from baseline scores to scores at 9 months
were assessed using Pearsons correlation coefficients.
159
Results: On the NSA-16, baseline and 9-month assessments were

obtained in 99 patients; on the various functional ratings, assessments
were obtained in 95-99 patients (except for FrSBe, n=74). Among the
NSA-16 symptom factors, score changes in Motivation showed correlation with changes on QLS, GAF, SOFAS, and LSP (P</=0.0001); FrSBe
(P</=0.001); and MCAS (P</=0.05). Communication correlated with GAF,
SOFAS, and FrSBe (P</=0.0001); LSP (P</=0.01); and MCAS and FNA
(P</=0.05). Affect correlated with GAF and SOFAS (P</=0.0001); FrSBe
(P</=0.01); and QLS and FNA (P</=0.05). The other symptom factors
(Social Activity and Motor Retardation) showed fewer significant correlations with the functional outcome ratings.
Conclusion: The NSA-16 symptom factors of motivation, communication, and affect showed the highest degree of correlation with the functional outcome measures used in these studies. Therefore, interventions
that yield improvements in these factors are more likely to lead to
improvements in function.
P-27-13
Complications during pregnancy and delivery in etiology
of schizophrenia
Jovo Djedovic
Specialized Psychiatric Hosp., Kotor, Serbia and Montenegro
Branislava Cizmovic, Nevenka Duletic, Aleksandar Tomcuk, Nadja
Sevaljevic
Introduction: Schizophrenia (or more precisely - the schizophrenia
group) represents a complex neuropsychiatric syndrome whose etiology is
still insuficiently researched. Among etiological factors that hold an
important place in contemporary researches of this disorder, the most
prominent are: Impact of altered genetical expression, viral infection and
complications during pregnancy and delivery. We are still unable to precisely determine the etiological relationship between perinatal pathology
and occurance of schizophrenic process in late adolescence. Possible
explanations, present in contemporary scientific literature, go into two
different directions: 1. Deviant genetic expression, as well as the effects
of other pathologic processes (e.g. viral infections) which create disposition for schizophrenia, create a greater possibility for occurance of gestation or perinatal complications. 2. Perinatal complications lead to cerebral
hypoxia while some authors beleive that the regions most susceptible to
this pathological process are hipocampus and limbic alocortex because of
their vicinity to incisura tentorii whose demages are related to schizophrenic psychosis from long time ago. Our paper comprises a retrospective study of 60 patients hospitalized at the Female Acute Ward of
Psychiatric Hospital in Kotor, Montenegro, who were diagnosed with
schizophrenia folowing the WHOs ICD 10 criteria. During the research we
monitored the incidence of perinatal pathology within this inpatient population and noted the presence of nonfocal neurological signs (soft
neurological signs). We attempted to determine the correlation between
desease prognosis and this etiological moment which was pointed out by
T. J. Crow in his hipothesis about type I and type II schizophrenia.
160
P-27-14
The significance of viral infections in schizophrenia relapse
Jovo Djedovic
Specialized Psychiatric Hosp., Kotor, Serbia and Montenegro
Branislava Cizmovic, Nevenka Duletic, Aleksandar Tomcuk, Nadja
Sevaljevic
Ever since the making of first clinical pictures of psychotic process and distinguishment of a group of deseases which Kraepelin and Beluler named
Dementio precox and Schizophrenia respectively, we are attempting to
identify factors which cause this neuropsychiatric syndrome. Postulates of
the role of viral infections holds an important place among theories on
this subject metter. In this group there are several conceptual models
(retroviral infection, current or active viral infection, past viral infection,
virally activated immunopathology, etc). This paper represents a retrospective study of the relapse in schizophrena and schizoaffective psychosis who have been hospitalized at on the Female Acute Ward of the
Psychiatric Hospital in Kotor, Montenegro in first 10 months of the current year. During this period 62 hospitalized patients were diagnosed with
schizophrenia or schizoaffective psychosis, following the WHOs ICD 10
diagnostic criteria. In addition to classical somatic, neurological and psychiatric examination, the hospital treatment encompassed diagnostic
evaluations as well, which included a standard laborathory analyses. The
following values were monitored: sedimentation rate, leukocyte count
(lymphocyte and polymorphonuclears), value of fibrinogen in serum and
C-reactive protein, and their dynamics in relation to the actual mental
state of the patient.
BRAIN FUNCTION - Poster
P-06
Brain Function
T8 Brain Function
P-06-01
SPECT evaluation of the brain in patients with obsessivecompulsive disorder before and after drug therapy preliminary results
Raquel Teresa Zamora Cabral
CAPTA, Montevideo, Uruguay
Fernando Mut, Mario Beretta
Introduction: The Obsessive Compulsive Disorder (OCD) has been studied for several years in an attempt to find its neurobiological substrate.
Quite characteristic findings have been reported using brain single photon emission computed tomography (SPECT) with perfusion agents, primarily revealing hyperactivity of the frontal cortex, cingulate gyrus, caudate nucleus and hippocampus, together with flow reduction following
SSRI therapy. The scarcity of the research conducted in Latin America
motivated us to undertake this study.
Method: Objective: to assess any changes in the brain perfusion patterns
before and after therapy in a population of patients presenting with a
diagnosis of OCD. Material and methods: 15 OCD (DSM IV) patients
underwent baseline SPECT (8 females and 7 males, aged 218 years). Six
of them were re-evaluated 12 months after starting with SSRI therapy. A
standard dose of 925 MBq (25 mCi) of 99mTc-ECD was injected intravenously. A two-headed gamma chamber equipped with ultra-high resolution collimators, using 360 rotation, 120 angular steps and 15 sec/step
in a 64 x 64 matrix and a 1.5 magnification factor. Transaxial tomograms
were reconstructed using filtered back-projection (Metz). Changs method
was applied to correct attenuation. Images were evaluated qualitatively
by two observers that compared the pre- and post-therapy findings, correlating them with the patients clinical course.
Results: All therapy-nave patients showed hyperactivity of the frontal
cortical structures, anterior or posterior cingulate gyrus, caudate nucleus
and/or thalamus. Thalamic disorders proved to be highly specific. There
was correlation between the patients clinical improvement and total (2
cases) and partial (4 cases) normalization of thalamus images. Although
there was still evidence of increased uptake in the thalamus, it was
reduced as compared to pre-therapy images. The most significant
changes were recorded in the caudate nuclei. There were no non-responders in this group of individuals studied.
Conclusion: Functional imaging with brain SPECT and 99mTc-ECD provides an objective evaluation of regional cerebral blood flow (or metabolic)
changes occurring in OCD patients before and after SSRI therapy, shedding some light over these drugs regulating impact on the neural circuits
involved.
P-06-02
The effect of repetitive transcranial magnetic stimulation
on symptoms in obsessive compulsive disorder
Jan Prasko
Republic
Martin Bares, Tomas Novak, Miloslav Kopecek, Jiri Horacek, Beata
Paskova, Barbora Tislerova, Katarina Adamcova, Richard Zalesky
Introduction: Within a decade, the Repetitive Transcranial Magnetic
Stimulation (rTMS) was being used to treat depression and schizophrenia.
Antidepressant response has been reported in open and double-blind,
sham-controlled studies of depression. Less is known about rTMS efficacy
in the obsessive compulsive disorder.
Method: The aim of the randomized, double-blind, sham controlled
study was to compare the 2 and 4 week efficacy of the 10 sessions rTMS
with sham rTMS in serotonin reuptake inhibitor resistant OCD patient.
Thirty seven right-handed patients were randomly assigned to either
active rTMS or to sham. Active rTMS with the frequency of 1 Hz at 110%
of motor threshold was administered over the left dorso-lateral prefrontal
cortex. The same time schedule was used for sham administration. Thirty
three patients finished the study, three patients dropped out at the
beginning. Psychopathology was assessed by CGI, HAMA, Y-BOCS and
BAI before the treatment, immediately after the experimental treatment,
and 2 weeks after by an independent reviewer.
Results: Both groups improved during the study period but the treatment
effect did not differ between them in any of the instruments.
Conclusion: Low frequency rTMS administered over the left dorso-lateral prefrontal cortex during 10 daily sessions did not differ from sham
rTMS in facilitating the effect of serotonin reuptake inhibitors in OCD
patients. Supported by the research project No. 1M0517 MZCR, Czech
Republic.
P-06-03
Repetitive transcranial magnetic stimulation in obsessive
compulsive disorder
Gihan Medhat ElNahas
Institute of Psychiatry, Neuropsychiatry, Nasr City Cairo, Egypt
Introduction: Obsessive Compulsive disorder is characterized by recurrent intrusive thoughts, images, or feelings that lead to a repetitive and
ritualistic behavior, in an attempt to overcome the obsession-evoked anxiety. The neurobiological model of OCD emphasizes abnormal activity in
cortico-striato-pallido-thalamic circuit. Tanscranial Magnetic Stimulation
(TMS) resembles electroconvulsive therapy (ECT) in that both somatic
interventions alter neuronal activity and change emotions. Among OCD
patients, right prefrontal magnetic stimulation has been reported to bring
about significant improvement of symptoms compared to other sites of
TMS application. This study attempts to: a) explore the therapeutic effects
of right prefrontal rTMS on OC symptoms and b) the duration of such
therapeutic effects through follow-up assessments.
Method: Fifteen adult patients suffering of primary OCD were assessed
for demographic, baseline illness characteristics as well as anxiety severity.
Patients who consented were given 7-10 sessions of right prefrontal
rTMS, and followed up for OCD and anxiety severity at 3rd, 6th, final sessions and at 24 weeks post-therapeutic.
Results: Results reveal that OCD patients improved significantly on right
prefrontal rTMS as regards compulsive and anxiety symptoms. The lasting
therapeutic effects of rTMS are a very promising finding, which needs to
be replicated and interpreted.
Conclusion: To the knowledge of the researcher, this finding hasnt been
reported earlier, its replication might denote a new privilege to TMS, not
only as an antiobsessional, but may be as a maintenance or long-acting
antiobsessional therapy.
References: Greenberg B, George M, Martin J et al, 1997: Effect Of
Prefronal Repetitive TMS on OCD: A preliminary Study. Am J Psychiatry;
154: 867-869. George M, Lisbany S, and Sackeim H, 1999: TMS:
Application in Psychiatry. Arch Gen Psychiatry; 56: 300-311. Okasha A, ElMahalawy N, El-Nahas G, et al, 2000: Cognitive Dysfunction in OCD. Acta
Psych. Scand; 101: 281-285
P-06-04
Altered expression and activation of phospatidylinositol
3-Kinase (PI3K) in postmortem brain of depressed suicide
subjects
Yogesh Dwivedi
University of Illinois at Chic, Psychiatry, Chicago, USA
Ghanshyam Pandey
Introduction: Phosphoinositide (PI) signaling has become a very important part of signal transduction research in recent years. PI3-kinase
(PI3K)/protein kinase B is one of the key signaling pathways involved in
many physiological functions in brain, including cell growth and differentiation, neurite outgrowth, membrane trafficking, and cytoskeletal organization. The PI3-kinase pathway is utilized by many growth factors to
mediate cell survival, or inhibition of apoptosis, for several neuronal subtypes. The enzyme PI3K is a heterodimeric protein complex consisting of
a 110-kDa catalytic subunit (p110) and an 85-kDa regulatory subunit
(p85). When recruited to an activated cognate receptor by the p85 regulatory subunit, the p110 catalytic subunit phosphorylates its main substrate, PIP2, to generate PIP3. Thus, both catalytic p110 and regulatory
161
p85 subunits are critical in mediating PI3K action. PIP3 then activates
PI-dependent protein kinase-1 (PDK-1). Protein kinase B, also known as
Akt, is the most important target of PI3-kinase. The present study examines whether PI3K is involved in the pathophysiology of depression.
Method: This study was performed in postmortem brain of depressed
suicide (n = 11) and nonpsychiatric control subjects (n = 11). Postmortem
brain samples were obtained from the Maryland Psychiatric Research
Center. The psychiatric diagnosis of subjects was performed according to
DSMIV criteria. Activation of PI3K was determined by enzymatic assay,
whereas mRNA and protein levels of various isoforms of regulatory and
catalytic subunits of PI3K were determined by competitive RT-PCR and
Western blot, respectively.
Results: It was observed that catalytic activity of PI3K was significantly
reduced in PFC and hippocampus of depressed subjects as compared with
nonpsychiatric control subjects. Competitive PCR analysis revealed significantly and selectively reduced mRNA expression of only the regulatory
p85 beta and catalytic p110 alpha and p110 gamma subunits in PFC and
hippocampus of depressed subjects. Reductions in these catalytic and
regulatory subunits were accompanied by reductions in their respective
protein levels. These changes were not related to postmortem interval,
age, or gender of subjects.
Conclusion: Our findings of reduced activation and expression of specific
PI3K regulatory and catalytic subunits demonstrate abnormality in this
signaling pathway in postmortem brain of depressed subjects and suggest possible involvement of aberrant PI3 kinase signaling in pathogenic
mechanisms of depression.
P-06-05
Influence of solvent inhalation on brain structure and
animal behavior
Nana Japaridze
Institute of Physiology, Neuroanatomy, Tbilisi, Georgia
Lia Gelazonia, Manana Dashniani
Introduction: Inhalation of the commercial products containing aromatic
hydrocarbon toluene by adolescents is a common form of drug abuse and
leads to atrophy of the cortex and hippocampus, decrease of the caudate
nucleus volume in human and experimental animals.
Method: To reveal the structural basis of these alterations and to investigate neurotoxic effect of toluene on the memory and learning processes,
toluene inhalation was applied in young rats, one month age after birth,
for 40 days, six days per week, for approximately 3-4 min, until the sidewise position in the closed glass container, in which air was saturated with
the toluene vapors. The data were obtained from 3 animal groups:
(i) - control, (ii) - experimental, (iii) - sham experimental - animals to
exclude an influence of the oxygen deficiency in closed container.
Assessment of the neurons quantity in hippocampus, motor cortex and
neostriatum was made according to the fractionator approach method
on the Nissl stained brain sections. Behavior and capacity for habituation
to the environment were tested in the Open Field, while the regularities
of the motor response learning were examined in condition of Morris
Water Maze. Statistical evaluation of the data was made with t-test and
Wilkocson-Mann-Whitney U-criterion.
Results: There were no differences between the results in (i) and (iii) animals. The data obtained in (ii) animals demonstrate loss of principal cells
by 26% in CA3 field of hippocampus and large pyramidal cells of motor
cortex by 45% against the (ii) animals. The cellular structure of rat neostriatum does not change during toluene intoxication. In the Open Field,
the capacity for habituation to the environment confirmed to similar rules
and did not differ in animals of (i) and (ii) groups. At the same time in the
Morris Water Maze animals of (ii) group reached the task learning criterion at 7th day, while the (i) rats - at 3rd day. Respectively, number of the
errors before the task learning to criterion in the (i) and (ii) animals differed significantly (P=0.05).
Conclusion: Toluene intoxication in young rats affects the structure of
the hippocampus, motor cortex and hampers the motor response learning, which points at a deficit in the non-declarative memory.
162
P-06-06
Structural changes provoked by hypokinetic stress in limbic and motor regions of rat brain
Mzia Zhvania
Institute for Physiology, Neuroanatomy, Tbilisi, Georgia
Introduction: The hypokinetic stress provokes many alterations in different systems of organism, elucidation of which are necessary for understanding its mechanism.
Method: The structural changes caused by hypokinetic stress in the limbic (hippocampus, piriform, cingular and enthorinal cortex, lateral and
central nuclei of amygdale) and motor regions (nucleus caudatus, motor
cortex) of rat brain were investigated at the light and electron microscopic
level. The quantitative electron-microscopic analysis of different forms of
synapses was also made. The experimental Wistar rats (adult males) were
placed in plastic cages where the distance between the body of animal
and wall wasnt exceeded 3-4 cm. As control were used (1) normal rats
and (2) rats from non-stress hypokinetic conditions (ACTH level in
blood plasma of these animals were the same as in normal rats). The
brains of experimental rats and rats from 2-th control group were investigated 40 days after restriction of movement.
Results: In experimental animals major changes were: first, in amygdale,
than in hippocampus (predominantly in CA1) and piriform cortex, lesser
in cingular and enthorinal cortex; almost normal was nucleus caudatus;
there were no changes in motor cortex. In amygdale about 35% of neurons (predominantly interneurons) were changed. The major alterations in
limbic zones were: chromatolysis or necrosis of some cells, myelin-,
osmiophilic or membrane-like formations in the perikarion, dendrites and
synaptic terminals, swelling of some dendrites, flattening of some spines,
changes in spine apparatus, dark degeneration of several synapses, polymorphism or agglutination of vesicles, true increase of the number of terminals with dense core vesicles (usually characterized as catecholaminecontained), increase of the number of synaptic terminals without active
zone, decrease of the quantity of synapses with flattened vesicles, true
increase of the number of astrocytes, including satellites. Such changes
arent in the amygdale of rats submitted to non-stress hypokinesia:
they have less prominent alterations, which are concentrated predominantly in nucleus caudatus. Thus, hypokinesia reinforced by stress, causes
significant changes in limbic zones and non-stress hypokinesia provokes less prominent changes - mostly in motor structures.
Conclusion: Thus, hypokinesia reinforced by stress, causes significant
changes in limbic zones and non-stress hypokinesia provokes less
prominent changes - mostly in motor structures.
P-06-07
Brain functional connectivity in patients with panic disorder
Peter Sos
Psychiatric Center, Prague, Czech Republic
Martin Brunovsky, Jan Prasko, Tomas Novak
Introduction: The aim of our study was to map the changes of the brain
functional connectivity in panic disorder (PD) patients in compare with
healthy controls. We supposed to detect lower functional connectivity in
the frontal brain regions of PD patients. The asymmetry of frontal alpha
power in PD patients was demonstrated [1Wiedemann et al., 1999]. PD
patients have a lower degree of inter-hemispheric functional connectivity
in the frontal region and intra-hemispheric functional connectivity in the
bilateral temporal region [2Hanaoka et al. 2005]. An area of decreased
metabolism was found in the region of the left precentral and postcentral
gyri [5Sakai et al. 2006].
Method: A group of 33 patients treated at day-care department of the
Prague Psychiatric Centre for PD with or without agoraphobia (meeting
the ICD-10 criteria), mean duration of the disorder 9.26.3 years s.d.,
without a diagnosis of depression (9 men and 24 women, average age
33.510.3 years s.d), medicated with SSRI and benzodiazepines (n=16)
and non-medicated (n=17). The control subjects consisted of 33 healthy
volunteers (9 men and 24 women, mean age 31.810.2 years s.d). The
control group was not significantly different from the PD group in age or
gender. EEG data were recorded in the resting state with a 19-channel
electroencephalograph. 30 artefact-free epochs (2 seconds each) per subject were selected by visual inspection of EEG recordings. Inter and intra-
hemispheric coherence were measured between the 19 electrode pairs.

Data were banded into delta, theta, alfa1, alfa2, beta1, beta2 and beta3
frequency band [4Herrmann et al., 1980]. Fishers Z transformation was
used to normalize the distribution of coherence values. Differences
between the PD patient group and the control group were analyzed by
analysis of variance (ANOVA).
Results: In PD patients we found a decrease in inter-hemispheric prefrontal (F3-F4) p=0.002 and frontal (F7-F8) p=0,004 coherence in compare with healthy controls. As well as decrease in intra-hemispheric left
prefronto-frontal (F1-F7) p=0.001 and right prefronto-frontal (F2-F8)
p=0.03 coherence in PD patients was found. Decreases of EEG coherence
were evident in the all measured frequency bands, but significancy
appeared only for alpha bands.
Conclusion: Our study identified a significant decrease of frontal intra
and inter-hemispheric functional connectivity in PD patients in comparison
with the healthy controls. These data provide further support for the
hypothesis of frontal brain asymmetry in panic disorder patients. Further
studies are needed to clarify the relationship between EEG coherence and
neuroanatomical findings. This study was supported by the project CNS:
MSMT CR 1M0517
References: 1Wiedemann G, Pauli P, Dengler W, Lutzenberger W,
Birbaumer N, Buchkremer G. Frontal brain asymmetry as a biological substrate of emotions in patients with panic disorders. Arch Gen Psychiatry
1999;56:78-84. 2Hanaoka A, Kikuchi M, Komuro R, Oka H, Kidani T,
Ichikawa S. EEG Coherence Analysis in Never-Medicated Patients with
Panic Disorder. Clin EEG Neurosci. 2005;36:42-48. 3Davidson RJ, Ekman
P, Saron CD, Senulis JA, Friesen WV. Approach-withdrawal and cerebral
asymmetry: emotional expression and brain physiology. I. J Pers Soc
Psychol. 1990;58:330-41. 4Herrmann WM, Fichte K, Kubicki S. Definition
von EEG-Frequenzbnder aufgrund strukturanalytischer Betrachtungen.
In: Faktorenanalyse und Variablenbildung aus dem Elektroencephalogramm. Kubicki S, Herrmann WM, Laudahn G (ed.). Stuttgart,
Gustav Fischer, 1980. 5Sakai Y, Kumano H, Nishikawa M, Sakano Y, Kaiya
H, Imabayashi E, Ohnishi T, Matsuda H, Yasuda A, Sato A, Diksic M,
Kuboki T. Changes in cerebral glucose utilization in patients with panic
disorder treated with cognitive-behavioral therapy. Neuroimage.
2006;33:218-26.
P-06-08
Prenatal stress in rats attenuates hippocampal long-term
potentiation and induces deficits in synaptic plasticity
Shiri Salomon
Hebrew University, Pharmacology, Jerusalem, Israel
Henry Matzner, Ramy Yaka, Marta Weinstock
Introduction: Behavioural stress modifies hippocampal plasticity through
NMDA receptor activation (Kim et al. 1996). Some studies have shown
that prenatally stressed (PS) rats exhibit spatial learning deficits. In the
present study we have investigated the effect of prenatal stress on spatial
learning, hippocampal long term potentiation (LTP) and on proteins
involved in the regulation of synaptic plasticity.
Method: Pregnant Wistar rats were stressed with 3 different stressors,
once daily during days 17-21 of gestation. In order to investigate spatial
learning and memory deficits, Morris water maze test was preformed on
male offspring at the age of 34 days. LTP was induced by high frequency
stimulation to Schaffer collateral in the CA1 region of control (C) and PS
hippocampal slices. Western blot analyses were performed on extracts of
hippocampal tissues taken from littermates of each group.
Results: PS rats showed significantly lower escape latencies and swam a
shorter distance to the platform than on the first day of the test, neither of these parameters decreased any further during the 3rd and 4th
days, in contrast to those in C rats, indicating impairment in the acquisition of the spatial memory task. High frequency stimulation in the CA1
region of the hippocampus produced LTP of fEPSPs in C rats. However,
the magnitude of LTP was significantly reduced in slices taken from agematched PS rats. No differences were found between PS and C rats in
paired pulse facilitation, indicating the absence of significant changes in
the control of neurotransmitter release. Western blot analyses reveled a
significant reduction in the expression of the NR2B subunit of the glutamate type NMDA receptor and the GluR1 subunit of the AMPA receptor,
both of which are important modulators of LTP. These changes were
accompanied by a remarkable increase in the scaffolding protein PSD95,
which interacts with the intracellular carboxy terminal domains of the
NR2 subunits.
Conclusion: The high levels of PSD95 may have contributed to the
impairment of LTP by disrupting the clustering of NMDA receptors in CA1
synapses. The alteration by prenatal stress in the relative amounts of scaffolding proteins and those which compose glutamate receptors could
explain the depression of LTP and impairment in the acquisition of spatial
learning.
References: Kim JJ, Foy MR, Thompson RF. Behavioral stress modifies hippocampal plasticity through N-methyl-D-aspartate receptor activation.
Proc Natl Acad Sci U S A. 1996 May 14;93(10):4750-3.
P-06-09
Modulation of autonomic balance by repetitive transcranial magnetic stimulation in patients with major
depression
Jagadisha Thirthalli
Kaviraja Udupa, Kishore Kumar, T. N. Sathyaprabha, T. R. Raju,
B. N. Gangadhar
Introduction: The cardiac autonomic involvement in depression has not
been conclusively established. Clinical improvement produced by antidepressant therapy might alter the autonomic balance. We planned to
investigate the effect of repetitive transcranial magnetic stimulation
(rTMS) on autonomic functions measured by heart rate variability (HRV) in
depression patients and compare with standard selective serotonin re-uptake inhibitors (SSRI) therapy.
Method: We recruited 40 patients suffering from Major depression
based on DSM-IV-TR. Their HRV as well as Hamilton depression-rating
scales (HDRS) were measured before and one month of therapy of rTMS
(n=25) or SSRI (n=15).
Results: Both the group of patients showed a significant clinical improvement as assessed by HDRS, which showed a decrease from their basal values of 18.56 2.46 to 9.55 2 and 17.71 2.96 to 8.48 2.88 in the
rTMS group and SSRI groups respectively. In terms of HRV, rTMS group
showed a significant increase in HF nu from 42.37 3.48 to 51.04 4.86
and a significant decrease LF nu & sympathovagal balance from 48.34
163
3.75 to 40.63 4.04 & 1.32 0.19 to 1.05 0.25 respectively. There was
no statistically significant difference in SSRI group in HRV parameters.
Conclusion: Though rTMS and SSRI are effective antidepressants, their
effects on HRV were different. rTMS modulated the cardiac autonomic
tone towards increasing the parasympathetic activity and decreasing the
sympathetic activity whereas SSRI did not modulate the neurocardiac regulation. Further studies with large sample size, biochemical and imaging
studies would throw more light into the mechanism of such modulation.
P-06-10
EEG responses to prefrontal low-intensity TMS
Seppo Khknen
Helsinki Univ. Centr. Hosp., BioMag Laboratory, Finland
Petri Savolainen, Juha Heiskala, Soile Komssi
Introduction: Left prefrontal TMS has been shown to have antidepressant effects. However, little is known about the effects of prefrontal TMS
on EEG activity. TMS combined with simultaneous EEG recording allows
one to investigate directly transient neuronal responses.
Method: Seven healthy subjects participated in the study. The left gyrus
medialis frontalis (BA 46) was identified and selected as stimulation site
with image-guided coil navigation system from individual MRI (eximia
NBS, Nexstim Ltd., Helsinki, Finland). Magnetic pulses were delivered with
a figure-of-eight coil with a loop diameter of 70 mm at the inter-stimulus
interval 3.3 s. Ten stimulus intensities (20-120% of the motor threshold;
MT) were used in a random order. At each intensity, 100 pulses were
delivered. The EEG was recorded with 60 scalp electrodes referred to the
forehead. The global mean field amplitude (GMFA) was used as an indicator of the strength of the evoked field. Linear regression analysis was
used to investigate the intensity dependence function.
Results: Excitation threshold of prefrontal cortex was 40% of MT as estimated with TMS-EEG. GMFAs at the peaks were linearly related to the
stimulus intensity i.e., TMS at higher intensity produced stronger neuronal
activity measured with EEG.
Conclusion: Prefrontal TMS combined with EEG may be potential a new
research tool for investigation of neuronal function of the prefrontal cortex for psychiatric disorders.
P-06-11
Repetitive transcranial magnetic stimulation (rTMS) in
Major Depressive Episode during pregnancy
Monika Klirova
Psychiatric Centre, 23, Prague 8, Czech Republic
Milan Kopecek, Tomas Novak, Vera Strunzova, Pavel Mohr
Introduction: For women diagnosed with reccurrent depressive disorder,
pregnancy poses a major treatment challenge. Apart from antidepressants, the most commonly used biological therapeutical method is ECT.
We believe that similar efficacy can be achieved using rTMS as a safer
option with substantially less side effects.
Method: Two pregnant females, with history of Reccurrent depressive
disorder and current symptoms of depression requiring treatment. The
first patient has been treated with escitalopram 15 mg p.d. + venlafaxine XR 225 mg p.d. She started rTMS at the 16th week of pregnancy.
Parameter settings were: 15 sessions, 20 Hz, left DLPFC, MT 100%, (train
2.5s, intertrain 30 s), 2000 pulses/session. Depressive symptoms were
assessed using MADRS. The second patient started stimulation at the 31st
week of pregnancy. She did not respond to the previous therapy with escitalopram 40 mg for 5 weeks with increase up to 60 mg p.d. for the following 2 weeks. She was switched to venlafaxine 225 mg p.d.at the time
of rTMS initiation. Parameter settings: 15 sessions, 1 Hz, right DLPFC, MT
100% (five 60 s trains with 60 sec intertrains, 300 pulses/session). The
settings were adopted from the Fitzgeralds study. This protocol was chosen
due to the low number of magnetic pulses during rTMS. Depressive symptoms were assessed using BDI, BAI.
164
Results: In both patients, a significant treatment response to rTMS treatment was observed. Baseline MADRS total score of the first patient was
33. The patient achieved remission after 3 weeks of rTMS (MADRS score
was 2). The remission was sustained for the remaining duration of pregnancy. The delivery was uncomplicated, the baby was healthy, breastfed.
Baseline BDI total score of the second patient was 29, BAI score 19. The
BDI and BAI scores decreased by 59 % and 58%, respectively after
3 weeks of rTMS treatment. The patient continued with venlafaxine XR
225 mg p.d. for the remaining duration of pregnancy. The delivery was
premature (36 week), the newborn being more irritated during the first
week; however, the baby fully recovered and is considered healthy.
Conclusion: No side or adverse effects associated with rTMS were
observed. Although no general recommendations can be drawn based on
our results, the case reports suggest that rTMS should be considered as
an effective and safe treatment option for depression in pregnancy. The
Project was supported by the CNPS and by the WFSBP.
References: Fitzgerald P.B., rTMS in the Treatment of Depression, Arch
Gen Psychiatry. 2003;60:1002-1008.
P-06-12
Deep brain stimulation in Huntingtons disease
Etienne Holl
Graz, Switzerland
A.K. Hdl, R.M. Bonelli
Introduction: Huntingtons Disease (HD) is a neurodegenerative disorder
leading to psychiatric and neurologic malfunction and progressive
dementia. Prominent neurologic symptoms are chorea, dystonia, and
parkinsonism in advanced stages. As shown in literature altered activity of
the globus pallidus externus (GPe) is responsible for these signs [1,2]. Only
transient improvement of choreatic symptoms are known with neuroleptic medication until now.
Method: To improve chorea and dystonia not enhancable with neuroleptic medication or benzodiazepines in patients with HD different parts of
the basal ganglia can be treated with deep brain stimulation (DBS).
Results: In 2006 Temel et al stimulated the GPe with motor and cognitive improvement in a transgenic rat model [3]. In case reports alleviation
of cognition differs after stimulation of the globus pallidus internus (GPi).
Hebb et al stimulated the GPi in one patient and described an alleviation
of HD-associated choreathetosis [4]. In 2004 Moro et al described a
decrease of chorea and dystonia by DBS of GPi in one patient. Outcome
of cognition was not mentioned [5].
Conclusion: GPe seems to be the better position for DBS due to the better
cognition performance but we need to demonstrate this in patients with
HD. DBS in the basal ganglia will be an exclusive treatment option for
patients without effect of medication in advanced HD.
References: [1] L. Ayalon, R. Doron, I. Weiner and D. Joel, Amelioration
of behavioral deficits in a rat model of Huntingtons disease by an excitotoxic lesion to the globus pallidus, Exp. Neurol. 186 (2004), pp. 46-58.
[2 ] A. Reiner, Can lesions of GPe correct HD deficits?, Exp. Neurol. 186
(2004), pp. 1-5. [3] Temel Y, Cao C, Vlamings R, et al. Motor and cognitive improvement by deep brain stimulation in a transgenic rat model of
Huntingtons disease. Neurosci Lett.2006;406(1-2):138-41 [4] Hebb MO,
Garcia R, Gaudet P, Mendez IM. Bilateral stimulation of the globus pallidus internus to treat choreathetosis in Huntingtons disease: technical
case report. Neurosurgery. 2006 Feb;58(2) [5] Moro E, Lang AE, Strafella
AP, Poon YY, Arango PM, Dagher A, Hutchison WD, Lozano AM. Bilateral
globus pallidus stimulation for Huntingtons disease. Ann Neurol. 2005
Jul;58(1):168
P-06-13
Electroconvulsive stimulations prevent stress-induced
morphological changes in the hippocampus
Ida Hageman
Righospitalet, Lab of Neuropsychiatry, Copenhagen, Denmark
Marianne Nielsen, Gitta Wrtwein, Nils Diemer, Martin Balslev Jorgensen
Introduction: The first episode of depression is often precipitated by
stress. Sustained stress can have numerous adverse effects on the brain.
Animal models of chronic stress, such as 21 days of restraint stress, show
that chronic stress alters neuronal morphology in the hippocampus.
Stressful conditions can induce retraction of apical dendrites and decrease
neurogenesis. These changes find their analogue in humans with depressive disorder and hippocampal shrinkage. In animals, stress-induced morphological changes can be reverted by antidepressant drugs.
Electroconvulsive treatment is one of the most effective antidepressant
treatments. Thus, the aim of the present study was to investigate whether
ECS could influence the length and branching of the hippocampal dendritic tree in normal as well as stressed rats.
Method: 24 male Sprague-Dawley rats were randomly assigned to the
following 4 groups: 1) 6 rats were subjected to 6 hours of restraint stress
daily for 21 days, 2) 6 rats underwent the same stress paradigm plus ECS
three times a week, 3) 6 rats received 3 weekly ECSs and 4) 6 rats were
left undisturbed in their cages except for daily handling. At the end of the
study brains were fixed and the dorsal hippocampus was cut into 100 m
sections and accordingly Golgi-impregnated. After processing wellimpregnated pyramidal CA3 neurons were drawn using a camera lucida
device. The number of dendritic branchpoints and the total length of the
dendritic tree were measured. Data was subjected to one-way analysis of
variance followed by Bonferonis post-hoc comparisons.
Results: Stress caused atrophy of the dendritic tree by significantly reducing the number of branchpoints and total length of the apical dendritic
tree. Concomitant treatment with ECS reverted this effect. ECS had no
effect on normal (non-stressed) rats.
Conclusion: The stress-induced structural remodelling of the dendritic
tree was prevented by ECS. The mechanisms underlying the antidepressant effects of electroconvulsive treatment is not fully elucidated. As suggested by this study ECS might act by reverting atrophic processes.
References: Watanabe Y, Gould E, McEwen BS (1992): Stress induces
atrophy of apical dendrites of hippocampal CA3 pyramidal neurons. Brain
Res 588: 341-344. Post RM (1992). Transduction of psychosocial stress
into the neurobiology of recurrent affective disorder. Am J Psychiatry 149:
999-1010. Videbech P, Ravnkilde B (2004). Hippocampal volume and
depression: A meta-analysis of MRI studies. Am J Psychiatry 161: 19571966.
165
GENETICS - Poster
P-07
Genetics
T9 Genetics
P-07-01
Genetic variants of SERT and DRD2 and executive functions
in impulsive/aggressive borderline personality disorder
Maria Leonor Bustamante
Santiago, Chile
M. Jimenez, F. Galleguillos, L. Pumarino, N. Roa, P. Iturra, A. Solari, J.
Villarroel, S. Jerez, H. Silva
Introduction: Variation on genes involved in monoaminergic pathways
could influence individual differences on executive functioning. Indeed,
association between the performance on different neuropsychological
tasks and some alleles of COMT, DRD2 and DRD3 has been demonstrated
in individuals with and without psychopathology. Our study is focused on
individuals with Borderline Personality Disorder (BPD) who had significant
levels of impulsivity/aggressiveness. We attempted to establish an association between their executive planning ability and variants of two genes
that have been associated with impulsive/aggressive behavior, the serotonin transporter (SERT) gene and the dopamine D2 receptor (DRD2)
gene.
Method: 37 BPD patients, classified as markedly impulsive/aggressive
according to the OAS-M interview were evaluated using the Tower of
London Test. They were genotyped using PCR and digestion with restriction enzymes. The polymorphisms considered in this study were the
5HTTLPR polymorphism of the SERT gene and the TaqI polymorphism of
the DRD2 gene.
Results: There were no significant differences between the different
genotype groups on their performance on the Tower of London Test.
Conclusion: The studied polymorphisms do not influence the executive
planning ability in impulsive/aggressive individuals. Although other measures of executive functioning are needed, the present results suggest that
the association between these variants and impulsivity/aggressiveness
may be mediated by factors other than alterations of the executive functions. Acknowledgments: This work was supported by FONDECYT
(Project 1030305) and by the University of Chile Clinical Hospital.
References: 1. Rosa et al., Am J Psychiatry (2004) 161:1110-2
2. Rybakowski et al., J Neural Transm (2005) 112:1575-82 3. Szekeres et
al., Am J Med Genet B (2004) 124B :1-5 4. Sakado et al., Am J Med
Genet B (2003) 121B:71-5
P-07-02
Combined genetic effect of the serotonin transporter and
HTR1A genes in clinical outcome of mirtazapine
Min-Soo Lee
Korea University, Psychiatry, Seoul, Republic of Korea
Rhee-Hun KANG, Myoung-Jin CHOI, Yoo-Jong JEONG
Introduction: This study was to analyze genetic variation at the 5-HTR1A
gene and its possible combined effect with the 5-HTTLPR polymorphism
at the serotonin transporter gene on clinical outcome in a major depressive disorder treated with mirtazapine.
entered the study. Prior to study entry, a 2-weeks-wash-out was performed. Their clinical symptoms were evaluated with the HAM-D-21
scales at baseline and after 1, 2, 4 and 8 weeks of treatment.
Results: A combined genetic effect of serotonin transporter and
5-HTR1A genes was found to affect the clinical outcome of MDD.
Homozyous patients carrying the risk genotype combination (SS/GG)
present a lower decreased HAMD score over 8 weeks (Time effect
F=33.674, p<0.000; Genotype effect F=10.228, p=0.001; Genotypetime interaction F=0.139, p=0.937). There is no significant interaction
between the genotype combination and time. These results may suggest
166
that the risk genotype combination(SS/GG) is affecting the clinical outcome, but not the pattern of clinical response to mirtazapine over time.
Conclusion: Homozyous patients carrying the risk genotype (SS/GG)
present a lower decreased HAMD score over 8 weeks. It means that the
risk genotype combination is affecting the clinical outcome to mirtazapine.
References: Arias et al., Evidence for a combined genetic effect of the
5-HT1A receptor and serotonin transporter genes in the clinical outcome
of major depressive patients treated with citalopram. Journal of
Psychopharmacology 19(2) (2005) 166-172
P-07-03
Abnormalities in behaviour and reduction in expression of
specific hippocampal genes by prenatal stress in female
offspring are reversed by neonatal handling
Yaarit Nachum-Biala
Hebrew University, Pharmacy School, Room 609, Jerusalem, Israel
Yoel Bogush, Shiri Salomon, Michal Linial, Marta Weinstock
Introduction: Prenatally stressed (PS) rats exhibit hyperanxiety, depressive-like behaviour and learning deficits(1,2). The present study investigated
the effect of neonatal handling (H)(1) from day 1-10 of age, on the development of the above mentioned abnormalities in behaviour and on hippocampal gene expression in female offspring.
Method: Pregnant Wistar rats were stressed daily during days 17-22 of
gestation with three different types of stressors, one in each day. Half of
the PS and control (C) offspring were handled daily for 3 minutes.
Behavioural tests consisted of evaluation of spatial memory in the Morris
water maze, hyperanxiety and depressive-like behaviour in the elevated
plus maze and the forced swimming tests, respectively. Gene analysis was
performed on the whole rat DNA AffyChip on 4 groups of 3 females
each. RT-PCR and Western-blot analysis verified the results in the genearray.
Results: In the behavioral tests we found that in female offspring H
reversed the hyperanxiety and depressive-like behaviour in PS rats but has
no effect on memory. Furthermore, we found in the gene analysis that
out of 9000 valid genes, 600 were differently expressed between PS and C.
out of those, 278 were up-regulated and 301 were down-regulated in PS
compared with C. From those that were down-regulated 93 genes were
restored to normal by H. These 93 genes can be classified into 3 main biological processes, all presynaptic nerve terminal-related that are active in
synaptogenesis, synaptic vesicle transport, and neurotransmitter release.
RT-PCR validated the results obtain from the genearray analysis, however
not all the changes in the proteins match the profile of those seen at the
mRNA level.
Conclusion: The study demonstrates that the alterations in gene expression by prenatal stress are related to impairment of the formation of new
synapses and neurotransmitter release. Neonatal handling enables recovery of new synaptic sites and the building of more effective synapse connectivity that is probably very local specific. The synaptogenesis and neurogenesis may contribute to the normalization of behaviour seen after H.
References: 1. Weinstock M. Alternation induced by gestational stress in
brain morphology and behaviour of the offspring. 2001. Prog Neurobiol.
65:427-451 2. Wakshlak A, Weinstock M. Neonatal handling reverses
behavioral abnormalities induced in rats by prenatal stress. 1990. Physiol
Behav. 48:289-92.
P-07-04
Trend for association of homozygous variants of DAT1 with
novelty seeking in healthy individuals
Alexandra Schosser
Univ. Hospital for Psychiatry, Dep. of General Psychiatry, Vienna, Austria
Karoline Fuchs, Theresa Scharl, Monika Schloegelhofer, Jochen Kindler,
Friedrich Leisch, Siegfried Kasper, Werner Sieghart, Harald N. Aschauer
Introduction: Cloninger (1993) hypothesized that the 4 heritable dimensions of personality are harm avoidance (HA), novelty seeking (NS),
reward dependence (RD) and persistence (PS), and NS is theoretically
related to dopaminergic, HA to serotonergic and RD to noradrenergic
activity. After not finding an association of DRD4 and DRD2 receptor
genes with personality in healthy individuals (Gebhardt et al. 2000), we
now focused on DRD3 and DAT1.
GENETICS - Poster
Method: We examined 89 (59 female and 30 male, mean age of 32.57)

normal volunteers using Cloningers Temperament and Character
Inventory (TCI). The normal volunteers as well as their family history
were free of any mental illness or psychiatric disease in first- and seconddegree relatives. All individual donated 20 cm blood by venipuncture.
Genomic DNA was extracted from lymphocytes using standard protocols.
Genotyping of the Ser9Gly polymorphism in exon 1 of the DRD3 gene
was performed using PCR-RFLP, whereas genotyping of the DAT1 repeat
polymorphisms was performed using PCR amplification following electrophoresis in an 8% acrylamide gel with a set of size markers.
Associations between TCI scores and DRD3 and DAT1 genotypes, and sex
were tested by Kruskal-Wallis Rank-Sum tests.
Results: We found significant association between sex and HA
(p=0.017), with women showing higher scores of HA. No association was
found between sex and any other personality dimension. Testing dimensions of the TCI for association with homozygous or heterozygous gene
variants, we found a trend for association of the homozygous variants
(5,5 and 6,6) of the DAT1 with NS (p=0.054). No such association was
found for the other personality dimensions, and for both homozygous
and heterozygous variants of DRD3.
Conclusion: In conclusion, we found a trend for association of the
homozygous variants of the DAT1 repeat polymorphism and personality
dimension of novelty seeking. However, correction for multiple testing
was not performed.
References: Cloninger CR, Svrakic DM, Przybeck TR (1993) A psychobiological model of temperament and character. Arch Gen Psychiatry
50:975-990. Gebhardt Ch, Leisch F, Schssler P, Fuchs K, Stompe T,
Sieghart W, Hornik K, Kasper S, Aschauer HN (2000) Non-association of
dopamine D4 and D2 receptor genes with personality in healthy individuals. Psychiatr Genet 10:131-137.
P-07-05
Enviromental and genetic factors: A study on Slovenian
population of suicide victims
Peter Pregelj
Un.Psychiatric Hosp.Ljubljana, KOKP, Slovenia
Martina Tomori, Galina Pungercic, Anja Videtic, Robert Dolnicar,
Radovan Komel, Tomaz Zupanc, Joze Balazic
Introduction: Several studies have been carried out to investigate how
genetic variants in one side and environmental factors on the other site
may influence susceptibility to suicide.
Method: In our study dual approach was used, we analyzed 5-HTTLPR
and VNTR polymorphisms in 35 suicide victims and 233 controls in a
Slovenian population to find a possible association of the polymorphisms
and suicidal behavior. On the other hand psychological autopsy was used
to evaluate environmental factors preceding suicide.
Results: No statistically important differences between genotypes of controls and suicide group, as well as no differences in allele distribution were
found. Haplotype frequency analysis showed no excess of particular haplotypes between the two groups. Our study showed no association of
serotonin transporter polymorphisms and suicide. We observed on the
other hand that more than 80% of all suicide victims had major stressors
reported in a month before suicide.
Conclusion: We have not observed differences in genetic variations
between subgroups in the observed genes on the contrary environmental
factors were observed.
P-07-06
Association between the serotonin transporter gene and
personality traits in borderline personality disorder
patients evaluated with zuckerman-kuhlman personality
questionnaire (zkpq)
Juan Carlos Pascual
Sta. Creu i Sant Pau Hospital, Psychiatry, Barcelona, Spain
Joaquim Soler, Thais Tiana, Montserrat Baiget, Anna Cortes, Montserrat
Goma, Enrique Alvarez, Victor Perez
and environmental etiology, the specific genetic influence have not been
extensively investigated (1). Some studies suggest that the serotonin
transporter gene (5-HTT) plays an important role in suicide, impulsivity or
affective instability suggesting it as a candidate gene for BPD (2). Short
allele (S) of the 5-HTTLPR polymorphism in the promoter region has
shown to be associated with impulsivity, aggressive behaviour, anxiety
and neuroticism. Of the VNTR polymorphism in intron 2, BPD patients
showed higher frequencies of the allele with the 10 repeat (3). The aim
of this study was to determine the association between 5-HTTLPR and
VNTR polymorphism of 5-HTT and personality traits in borderline personality disorder.
Method: A total of 65 BPD patients diagnosed by means of semi-structured interviews SCID-II and DIB-R were included. Two common polymorphisms of 5-HTT were genotyped: the 5-HTTLPR in the promoter region
and VNTR in intron 2. Personality traits were assessed by the ZuckermanKuhlman Personality Questionnaire (ZKPQ).
Results: Patients with L allele (L/S or L/L) in the 5-HTTLPR polymorphism
showed lower scores in the subscale of Liking Parties and Friends. Patients
with the allele with 10 repeat of the VNTR polymorphism, showed lower
scores in Impulsivity, Sensation Seeking and in the subscale Liking of
Parties and Friends.
Conclusion: The results suggest an association between the serotonin
transporter gene and some personality traits in BPD. This gene may play
a role in the aetiology of borderline personality disorder.
References: 1.- Skodol A, Siever L, Livesley W, Gunderson J. Pfohl Bruce,
Widiger T. The Borderline Diagnosis II. Biology, Genetics, and Clinical
Course. Society of Biological Psychiatry. 2002; 51: 951-963. 2.- Lesch KP,
Bengel D, Jeils A, Sabol SZ, Greenberg BD, Petri y cols. Association of anxiety- related traits with a polymorphism in the serotonin transporter gene
regulatory region. Science,1996; 27:1527-31. 3.- Ni X, Chan K, Bulgin N,
Sicard T, Bismil R, McMain S, Kennedy J. Association between serotonin
transporter gene and borderline personality disorder. Journal of
Psychiatric Research, 2006; 40: 448-453.
P-07-07
Attention deficit disorder: Genetic and possible attachment style contributions
Maria-Eugenia Moneta
University of Chile, Faculty of Medicine, Santiago, Chile
Francisco Rothhammer, Daniela Camponovo, Hugo Henriquez
Introduction: The present paper adds evidence to the discussion of the
hypothesis that genetic predisposition and environmental factors influence psychological development. We studied a group of children of high
socioeconomic status in Santiago de Chile diagnosed with ADHD from a
genetic and an attachment style point of view to evaluate to which
extend both factors may contribute to ADHD disorder.
Method: 20 children between 6 and 12 years old where selected from
a group with learning dishabilities from an upper class community in
Santiago. The presence or absence of attentional deficit with hyperactivity disorder (ADHD) was assessed through DSMIV scale and Child
Behavioural Check List (Achenbach, 1991). Attachment security level was
obtained applying the Security Scale from Kerns, Keplan and Cole (1996)
Results: Preliminary data show that a majority (82%) of the children
experimented a secure attachment. Nevertheless ADHD was diagnosed
in 40 % of children with learning dishabilities. Genetic studies revealed a
tendency of ADHD to be associated with DAT 1.10 and DRD4.7 polymorphisms.
Conclusion: Evidences obtained from this relatively small sample indicates the necessity of a multidisciplinary approach to study the interrelation between environmental factors, genetic contribution and learning
dishability problems during development leading to ADHD. With regard
to research on child health we suggest that knowledge about specific
genetic risks factors may help substantially to clarify environmental contributions such as attachment style.
Introduction: Although there is general consensus that Borderline

Personality Disorder (BPD) has a multifactorial etiology including genetic
167
GENETICS - Poster
P-07-08
A suggested endophenotype for suicide described in
suicide attempters
P-07-10
Psychiatric features associated with Fragile X Mental
Retardation 1 (FMR1) gene premutation condition
Dolores Saiz
Gregorio Maranon Hospital, Psychiatry, Madrid, Spain
Jeronimo Saiz-Ruiz
Cary Kogan
University of Ottawa, School of Psychology, Canada
Kim Cornish
Introduction: Suicide is one of the most relevant issues in modern psychiatry. It is one of the first causes of death and years of life lost in young
adults. The description of endophenotypes opens a new line of research
with good results in other mental disorders like schizophrenia.
Method: The aim of this study was to analyze different features among
suicide attempters with or without family history of suicide (including
attempts and or completed suicide), in order to define a phenotype that
could be related with the biological substrate of suicide. 534 suicide
attempters were recruited at the Emergency Room of a general hospital.
They were interviewed within 24 hours of the attempted. We performed
a univariate analysis with contingency tables and calculated statistic significance with Chi-square tests and Fisher exact tests. We analyzed each
variable separately and compare the values in patients with family history
of suicide (attempts and/or completed suicide) and in those without these
antecedents.
Results: The patients with family history of suicidal behaviour shows the
following features (p<0,001): method is overdose or cuts, patients are not
treated with mood stabilizers and they dont have family history of schizophrenia, affective disorders or other mental disorders (including unspecified mental diagnosis).
Conclusion: One endophenotype is suggested, in relation with family
history of suicide. This phenotype is mainly defined by variables related
inversely to treatment and mental disease in family. This work support,
the current hypothesis of suicide genetic transmission independently from
the heredity of mental diseases associated with this conduct.
References: Gottesman II, Gould TD. The endophenotype concept in
psychiatry: etymology and strategic intentions. Am J Psychiatry 2003;
160(4):636-645. Courtet P, Jollant F, Castelnau D, Buresi C, Malafosse A.
Suicidal behavior: relationship between phenotype and serotonergic
genotype. Am J Med Genet C Semin Med Genet 2005; 133(1):25-33.
Turecki G. Dissecting the suicide phenotype: the role of impulsive-aggressive behaviours. J Psychiatry Neurosci 2005; 30(6):398-408.
Introduction: Fragile X Syndrome (FXS) is a pervasive developmental disorder arising from the silencing of the FMR1 gene due to trinucleotide
repeat expansion. Affected, full mutation (FM) individuals, display a specific pattern of cognitive deficit concurrent with psychiatric symptoms
that include mood and anxiety disorders. In contrast to the FM condition,
little is known about psychiatric features associated with premutation
(PM) status. The paucity of data stems from a longstanding notion that
PM individuals are free of phenotypic effects because FMR1 gene expression is relatively intact. More recent studies are beginning to characterize
the cognitive phenotype of PM individuals. The goal of the present study
is to extend this knowledge base to investigate potential psychiatric features associated with PM status.
Method: As part of a larger study of psychiatric features of PM individuals,
we administered numerous measures of psychiatric functioning to a
group of thirty-one PM males aged 18 to 69 years as well as to 56 unaffected comparison males matched on age and IQ. A subset of these
measures focusing on mood and anxiety were included in the present
analysis. Specifically, self-report measures included the Liebowitz Social
Anxiety Scale (LSAS), the Rosenberg Self-Esteem scale, and the Hospital
Anxiety and Depression Scale (HADS). T tests for independent means
were conducted to compare mean scores on measures and their subscales
where appropriate.
Results: PM males demonstrated significantly elevated scores on the
LSAS - Fear/Anxiety subscale but neither the Avoidance subscale nor the
total score for this measure were significantly elevated as compared to
comparison males. Further analysis revealed that 24% of the PM males
exceeded the cut-off score on the LSAS for meeting diagnostic criteria for
Social Phobia as compared to 7.5% of the comparison group.
Interestingly, on a more general measure of anxiety, the HADS - Anxiety
subscale, no significant differences were observed. Similarly, the HADS Depression subscale revealed no significant differences between the two
groups. On a measure of self-esteem, PM males generally scored lower
than comparison males, indicating lower self-esteem in this group.
Conclusion: Measures of mood and anxiety revealed that PM status confers greater risk of experiencing fear in social contexts. Interestingly, PM
males were not more likely to avoid social situations despite their elevated
fear of social situations. These results are consistent with other studies
that describe social phobia as a central psychiatric condition common to
females with full mutation FXS.
P-07-09
Cytogenetic Regions of Interest (CROIs) analyzed with
Single Nucleotide Polymorphisms (SNP) microarrays in
Chilean children with autism spectrum disorders
Mario Valdivia
Universidad de Concepcion, Psiquiatria y Salud Mental, Chile
Gabriela Zegers, Gian Carlo De Ferrari, Luis San Martin, Andrew
Singleton, Mar Matarin, John Hardy
Introduction: Twin and family studies have provided compelling evidence
for a strong genetic component among autistic individuals. Multiple
genome-wide screens have found evidence for linkage to autism in several chromosomes. Likewise, cytogenetic abnormalities related to the
autistic phenotype have been reported in chromosomal regions overlapping known loci of significant linkage.
Method: We have begun to explore a sample of Chilean autistic children
for cytogenetical abnormalities with the aid of beadchips microarrays
(Illuminas Infinium-II Sentrix BeadChips) containing > 300.000 single
nucleotide polymorphisms (SNPs), which are increasingly used for wholegenome genotyping.
Results: Our results reveal several cytogenetical abnormalities in five out
of eight studied autistic children, including small duplications (15,000 140,000 bp) in chromosomes 1, 2, 10 and 12, as well a deletion in chromosome 9 (281,000 bp).
Conclusion: These preliminary results support the polygenic nature of
this neurodevelopmental disorder, and stress the need for further research
with larger samples of autistic children and their families.
168
P-07-11
Personality characteristics and 5-HTTLPR in patients with
chronic daily headache
Chung Tai Lee
Uijongbu St. Marys Hospital, Department of Psychiatry, Uijongbu
Gyeonggido, Republic of Korea
Hae Kook Lee, Jeong Wook Park, Yong Sil Kweon
Introduction: Chronic daily headache refers to a group of non-paroxysmal daily or near-daily headaches with peculiar characteristics, which are
highly prevalent in population of psychiatric clinics and primary clinics.
Serotonergic drug such as SSRI(paroxetin etc.) has been implicated to be
effective on chronic daily headache. Also, the relationship between serotonergic dysregulation and personality chraracteristics has been
described. The authors carried out this study to investigate the associaton
between chronic daily headache and serotonergic dysregulation by comparison of 5-HTTLPR & Tridimensional Personality Questionaire(TPQ).
Method: Eighty one patients with chronic daily headache by criteria(proposed by silberstein et al.,1994) and 100 healthy individuals who did not
have history of psychiatric illness were selected for comparison of 5-HTTLPR (assessed by PCR based method). Also, 45 patients group and 75 normal controls answered TPQ to evaluated the association between specific
component of personality characteristics and chronic daily headache.
GENETICS - Poster
Results: Although statistically significant differences in frequencies of

serotonin transporter gene genotype and allele between patients and
controls were not found, the analysis showed a trend that frequencies of
short alleles were higher in patients group. In analysis of TPQ, the novelty
seeking scores were lower and harm avoidance scores were higher in
patients group than normal controls.
Conclusion: Although there was limitation in generalization of our result,
this result suggested that chronic daily headache was associated with
serotonergic abnormalities. Further study with larger sample are need to
better understand of serotonergic abnormality in patients with chronic
daily headache.
References: (1) Stoltenberg SF, et al. (2002) Serotonin transporter promoter polymorphism, peripheral indexes of serotonin function, and personality measures in families with alcoholism. Am J Med Genet 114:230234 ; (2) Park JW, et al. (2004). Serotonin transporter polymorphism and
harm avoidance personality in chronic tension-type headache. Headache
44:1005-1009
References: Cornish, K., Manly, T., Savage, R., Swanson, J., Morisano, D.,
Butler, N., Grant, C., Cross, G., Bentley, L., & Hollis, C.P. (2005).
Association of the dopamine transporter (DAT1) 10/10-repeat genotype
with ADHD symptoms and response inhibition in a general population
sample. Molecular Psychiatry, 10, 686-698. Willcutt, E. G., Pennington,
B.F., Olson, R.K., Chhabildas, N., Hulslander, J. (2005). Neuropsychological analyses of comorbidity between reading disability and attention
deficit hyperactivity disorder: in search of the common deficit. Dev
Neuropsychol., 27(1), 35-78.
P-07-12
Response to methylphenidate according to the 9- and 10repeat allele of the DAT 1 and DRD 4 gene alleles in adults
with attention deficit hyperactivity disorder
Introduction: This aim of this survey is to determine the association of

genetic factors with presence of Common Mental Disorders and also
overall mental illnesses.
Method: This is a sub study form a larger survey entitled The Malaysian
Mental Health Survey (MMHS). Two genetic factors included in the MMH
survey were presence of family history of mental illness among the subjects and delayed parenting or being born for old parents. Presence of
common mental disorders (CMD) refers to presence of CIS-R diagnosis
alone whereas overall mental disorder refers to presence of CMD and all
other diagnoses given by psychiatrists, which includes psychosis.
Influences of the genetic factors on presence of Mental illnesses and CMD
were studied using logistic regression models
Results: Presence of family history of mental illness increased the risk of
CMD and also mental illnesses after adjusting for demographic factors.
The subjects born for old fathers also had elevated risk for mental illness
and CMD. When both the genetic factors were placed into one model,
family history was found to be a stronger factor. Delayed parenting was
found to be significant for CMD only and not for overall mental illness.
Conclusion: Presence of family history of mental illness in the family and
being born for aged parents were two important factors associated with
presence of CMD and mental illnesses. The final paper will discuss on
developed models and precise findings from the models.
Johanna Krause
Outpatient Clinic Psychiatry, Ottobrunn, Germany
Introduction: Relationships between methylphenidate (MPH) response
and polymorphisms of the dopamine transporter gene (DAT 1) in patients
with ADHD are described, but not with conclusive results (1); for DRD 4 a
blunted response of the 7-repeat to MPH has been reported (2). In this
study response to MPH was related to the DAT 1 and DRD 4 genotype in
adults with ADHD.
Method: In 27 adults with ADHD the genotype of the SLC6A3 promotor
VNTR polymorphism as well as polymorphisms of DRD 4 were assessed.
Patients were categorized as responder or non responder, according to
Clinical Global Impressions Scale.
Results: The two patients with 9-9 genotype of DAT 1 were non responders, no difference in response could be found between 9-10 and 10-10
carriers. Two patients were homozygote for the 7 allele of the DRD
4 gene, both were responders. No patients were heterozygote for the
7 allele.
Conclusion: The non response to MPH in patients with 9-9 alleles of DAT
1 gene is in accordance with earlier results in children (3). We observed
no influence of the 7 allele of DRD 4 gene on response, but studies with
more patients are needed.
References: 1. Krause J et al. World J Biol Psychiatry 2006; 7: 152-7 2.
Hamarman S et al. J Child Adolesc Psychopharmacol 2004; 14: 564-74 3.
Stein MA et al. Neuropsychopharmacology 2005; 49: 1874-82
P-07-13
The DAT 1 association with ADHD behavior is mediated by
reading ability in a general population sample
Kim Cornish
McGill University, Neurology/Neurosurgery, Montreal, Canada
Introduction: Attention deficit hyperactivity disorder (ADHD) and reading disability (RD) frequently co-occur in the child population and therefore raise the possibility of shared genetic aetiology.
Method: We used a Quantitative Loci Trait (QLT) approach to assess the
involvement of the dopamine transporter (DAT1) gene polymorphism in
mediating reading disability and poor attention in a general population
sample of primary school children aged 6 - 11 years in the U.K. The
potential confounding effects of IQ and chronological age were also
investigated.
Results: We found an independent association between the homozygous DAT1 10/10 repeat genotype and RD that was not accounted for by
the level of ADHD symptoms.
Conclusion: This findings suggest that the DAT1 gene polymorphism
may influence a common neural mechanism underlying both reading
acquisition and ADHD symptoms.
P-07-14
Association of genetic factors with presence psychiatric
disorder in Malaysian population- (the MMHS study)
Tishya Indran
Royal Adelaide Hospital, Australia
Saroja Krishnaswamy, Kavitha Subramaniam, Abdul Aziz Jemain, Abdul
Hamid Abdul Rahman, Vikram Patel
P-07-15
Polymorphisms of Dysbindin Gene (DTNBP1) and schizophrenia in the korean population
Tae-Youn Jun
Catholic University of Korea, Dept. of Psychiatry, Seoul, Republic of
Korea
Won-Myong Bahk, Jeong-Ho Chae, Chi-Un Pae, Young-Eun Jung,
Byung-Wook Lee, Seung-Kyu Bang, Young Sup Woo
Introduction: The gene encoding the dystrobrevin binding protein
(DTNBP1) has been implicated in the pathogenesis of schizophrenia by
several association studies. The dysbindin gene is located at chromosome
6p22.3, one of the most promising susceptibility loci in linkage studies of
schizophrenia. The aim of this study is to determine whether DTNBP1 is
associated with schizophrenia in the Korean population.
Method: 452 Korean patients with schizophrenia in accordance with
DSM-IV criteria and 442 Korean healthy individuals matched to age and
sex participated in this study. We examined two single nucleotide polymorphisms (p1635, p1325) using Pyrosequencing system, and examined
allele, genotype and haplotype association with schizophrenia. The results
were analyzed by chi-square test and Fishers exact test.
Results: There were no significant differences in genotype and allelic frequencies of SNP p1635 between cases and controls (x2 = 1.21, df=2,
p=0.655, x2 = 0.575, df=1, p=0.448). However, SNP p1325 reached significance. The frequency of the rare allele was significantly higher in cases
compared with controls (x2 = 6.35, df=2, p=0.042, x2 =4.41, df=1,
p=0.036). Two SNP haplotype AC, GC were not associated with schizophrenia, but SNP haplotype AT was significantly in excess in cases compared with controls. (x2 = 4.41, df=1, p=0.036)
169
GENETICS - Poster
Conclusion: These results provide the support for DTNBP1 as a susceptibility gene for schizophrenia in the Korean population. In the future, further studies should be needed to confirm the relationship between genetic
variation in DTNBP1 and the phenotype of schizophrenia.
References: Williams NM, Preece A, Morris DW, Spurlock G, Bray NJ,
Stephens M, Norton N, Williams H, Clement M, Dwyer S, Curran C,
Wilkinson J, Moskvina V, Waddington JL, Gill M, Corvin AP, Zammit S,
Kirov G, Owen MJ, ODonovan MC. Identification in 2 independent samples of a novel schizophrenia risk haplotype of the dystrobrevin binding
protein gene (DTNBP1). Arch Gen Psychiatry. 2004 Apr;61(4):336-44.
Kirov G, Ivanov D, Williams NM, Preece A, Nikolov I, Milev R, Koleva S,
Dimitrova A, Toncheva D, ODonovan MC, Owen MJ. Strong evidence for
association between the dystrobrevin binding protein 1 gene (DTNBP1)
and schizophrenia in 488 parent-offspring trios from Bulgaria. Biol
Psychiatry. 2004 May 15;55(10):971-5.
P-07-16
Study on differences in tumor suppressor adenomatous
polyposis coli gene polymorphisms between schizophrenia
and colon cancer patients
Seong Hwan Kim
Dong-a University Hospital, Psychiatry, BUSAN, Republic of Korea
H. Kim, H. Jung
Introduction: Low incidence of cancer in patients with schizophrenia is
epidemiological puzzle in psychiatric field over decades. It has been proposed that genetic predisposition toward schizophrenia may be associated with reduced vulnerability to cancer. Adenomatous polyposis
coli(APC), a tumor suppressor gene, has been studied for its role in cancer development. APC is also known to be involved in cell adhesion and
neuronal function.
Methods: In order to analyze the genetic difference between schizophrenia and colon cancer patients, polymorphisms of APC gene was studied
from 248 schizophrenia patients, 248 colon cancer patients, and 248
control subjects in Korean population.
Results: Two SNPs(rs2229992, rs456899) on the APC gene were investigated. The genotype, allele, and haplotype of the APC polymorphisms in
patients with schizophrenia were not significant different from those of
controls. When compared patients with colon cancer, the schizophrenic
patients showed significantly more frequent in rs2229992 CT/TT genotype(odds ratio 2.179, 95% confidence interval(CI)=1.20-3.959) and the
male schizophrenic patients revealed significant differences in T-G haplotype(odds ratio 2.5915, 95% CI=1.4677-4.5759), after adjusting for age
and sex.
Conclusion: The present results suggest that the APC polymorphisms
found in schizophrenic patients may be associated with reduced vulnerability to colon cancer.
References: Catts VS, Catts SV. Apoptosis and schizophrenia: is the
tumour suppressor gene, p53, a candidate susceptibility gene? Schizophr
Res 2000; 41:405-415.Mortensen PB. The incidence of cancer in schizophrenic patients. J Epidemiol Community Health 1989; 43:43-47.Park JK,
Lee HJ, Kim JW, Park YH, Lee SS, Chang HI, et al. Differences in p53 gene
polymorphisms between Korean schizophrenia and lung cancer patients.
Schizophr Res 2004; 67:71-74.Cui DH, Jiang KD, Jiang SD, Xu YF, Yoa H.
The tumor suppressor adenomatous coli gene is associated with susceptibility to schizophrenia. Mol Psychiatry 2005; 10:669-677.
170
NEUROIMAGING - Poster
P-08
Neuroimaging
P-08-01
Determination of NADH by laser-induced fluorescence spectroscopy: Applications in preclinical neuroscience
Andre Rex
Freie Universitt Berlin, Institute of Pharmacology, Germany
Melanie Hamann, Angelika Richter, Frank Fink, Heidrun Fink
Introduction: There is an increasing need for continuously monitoring
changes in brain metabolism and neuronal activity, respectively. The
majority of the energy, which is produced in neurons, is necessary for the
maintenance of the physiological neuronal activity. The extent of the
energy production is thus closely coupled to the neural activity.
Method: Measurement of NAD(P)H fluorescence by laser-induced fluorescence spectroscopy and with small glass fibre probes allows the determination of the mitochondrial activity, and therefore neuronal activity
indirectly, in the brain with high temporal and spatial resolution (Rex &
Fink, 2006).
Results: In vitro, dependence between the NADH concentration and
NADH fluorescence was proven. Ex vivo investigations showed that under
the selected spectroscopic conditions predominantly NADH fluorescence
contributes to the fluorescence of the tissue and that the fluorescence
intensity differs between brain regions. We could show in anaesthetized
rats that the fluorescence intensity of NADH in the cortex is inversely proportional to the metabolic activity and that changes in the NADH fluorescence due to haemodynamical effects altering the optical properties of
the tissue can be excluded. In further in vivo experiments administration
of a serotonin 1A receptor agonist with known anxiolytic activity and
inhibitory effects on neuronal activity in the hippocampus causes a
reversible increase in the intensity of hippocampal NADH fluorescence in
pharmacologically relevant doses. In awake and freely moving mutant
dtsz hamsters, a model of paroxysmal dystonia, we could measure
reversible changes of the NADH fluorescence during a dystonic episode.
The magnitude of the change corresponds to the severity of the dystonic
episode.
Conclusion: The laser-induced fluorescence spectroscopy of the intrinsic
and mainly mitochondrial bound NADH is a versatile applicable and reliable method which allows the spatial and temporal characterization of
the metabolic state and thus the neuronal activity in the brain in vitro and
in vivo.
References: A. Rex, F. Fink (2006)Las.Phys.Lett.,3:452-9.
P-08-02
Early cerebral grey matter excess in basal ganglia after early
treatment in first-onset, never-medicated schizophrenia
Yi Deng
Rm 1206, Block B, Healthy Gard, North Point, HK Island, China, Peoples
Republic of : Hong Kong SAR
Cheung Vinci, Charlton Cheung, Eric Y. H. Chen, Jack T. K. Tsang, Jason
C. H. Wong, Lawrance Yip, Kin S. Tai, John Suckling, Grainne M.
McAlonan, Siew Chua
Introduction: In the early weeks following neuroleptic treatment,
patients never previously been exposed to antipsychotic medication and
presenting with first-episode of schizophrenia may already demonstrate
brain volumetric differences.
Method: We used a comprehensive computational morphometry analysis of the brain. 38 individuals with first-episode psychosis were balanced
for age, sex, handedness, ethnicity, height, education in years, paternal
socio-economic status and PANSS score. They were a consecutive series
presenting to their local hospital for treatment. BAMM (Brain activation
and morphological mapping) software was used to measure grey matter,
white matter and CSF volumes. 12 were treated with neuroleptics (NT)
and 26 were neuroleptic-nave (NN). The NT group had been scanned in
the earlier stage of the project as a pilot group and did not differ in MRI
scanning parameters. Groups did not differ in age, sex, socioeconomic
class, handedness, ethnicity. In the NT group, significant clusters of volume
excess in grey matter was detected bilaterally in the caudate, putamen, cin-
gulate, cerebellum, and brainstem after around 18 days of neuroleptic

treatment. Region-of-interest measurement of the caudate using
T1 scans, 1.2mm, contiguous, 128 slices was done by a single operator
blind to group membership.
Results: It showed caudate volume significantly larger by 16% (on the
left, p 0.012, 2 tailed) and 13% (on the right, p 0.028, 2 tailed) in the NT
group.
Conclusion: This is the first study to demonstrate that basal ganglia and
extrastriatal grey matter excess is likely to occur early on within three
weeks of initiating neuroleptic treatment.
P-08-03
Delayed neurological syndrome secondary to carbon
monoxide intoxication. Case report
Cristina Hidalgo
Mutual de Seguridad Hospital, Neurology and Neurosurgery, Santiago,
Chile
Carlos Flores, Ciro Pereira
Introduction: Carbon Monoxide (CO) intoxication is an important cause
of morbimortality worldwide. The Late Neurological Syndrome is a rare
complication (prevalence less than 1%). This syndrome presents 2 to
40 days after CO exposure, and after apparent symptom improvement.
Diagnosis is clinical and neuropsychometric.The syndrome presents memory loss, confusion, ataxia, seizures, sphincter incontinence, emotional
distress, disorientation, hallucinations, Parkinsonism, mutism, cortical
blindness, psychosis, gait and motor disturbances. CT in severe cases
shows bilateral hypodensity of Globus Pallidus. MRI shows symmetric and
diffuse white substance lesions, predominantly periventricular.There is no
evidence in relation to treatment. 50 to 70% of the patients recover within a year
Method: Case Report
Results: N.P.Male, 54 years old, Security guard. No previous medical history. On 10/14/06 he suffers carbon monoxide (CO) intoxication trying to
get warm in a closed space. He is admitted to the Emergency Ward with
quantitative and qualitative consciousness involvement. Saturation 93%.
Laboratory Exams: Carboxyhemoglobin (HbCO) 3.7 %, Creatine
Phosphokinase (CPK) 4679, Normal (N) blood gases, Lactic Acid (N), CT
Brain imaging showed a slight hypodense area in the lentiform nuclei,
EKG (N), Neurological exam (N). He was discharged in good general conditions. Twenty days after discharge he visits again due to memory disturbances, disorientation and progressive psychomotor agitation. Neurology
evaluation shows an apathetic patient with bizarre behavior, who does
not obey simple orders, changes in memory, and loss of sphincter control.
An MRI is performed; showing symmetric lesions in both globus pallidus,
diffuse changes of white substance in both hemispheres, with involvement of both semioval centers. The decision to start antioxidant use is
made, together with polyunsaturated long chain fatty acids, Memantine
and hyperbaric chamber as therapeutic measures.
Conclusion: In spite of the low prevalence of the Late Neurological
Syndrome, we must be alert to suspect it, and use all the available
resources to prevent and manage it. Even if no evidence exists in treatment of this pathology, based on physiopathological knowledge we
should try to attempt management by means of hyperbaric chamber,
Memantine, antioxidants, and longchain poli-insaturated fatty acids.
References: 1. Kao L, Nanagas K. Toxicity Associated with Carbon
Monoxide. Clinics in Laboratory Medicine 2006; 26:99-125. 2. Eicher T,
Avery L. Toxic Encephalopathies. Neurologic Clinics 2005; 23:353-376.
3. Vila J, Meli F, Serqueira O. Revista de Neurologica Argentina. 2005;
30:118-123. 4. Judge B, Brown M. To Dive or Not to Dive? Use of
Hyperbaric Oxygen Therapy to Prevent Neurologic Sequelae in Patients
Acutely Poisoned with Carbon Monoxide. Annals of Emergency Medicine.
2005; 46:462-464.
171
P-08-04
Von Hippel Lindau disease: Case history and review of the
literature
Jorge Ibanez Dominguez
IVSS, Psychiatry, Caracas, Venezuela
Yamilet I., Romero L., Adolfo Rolando Alvarez, Pastor Oropeza Herrera,
Alexis Chirinos, Maria Cristina Ortiz
Introduction: Von Hippel-Landau Disease is rare. Its origin is a genetic
flaw that originates tumors in several organs, e.g. cerebellum
(Hemangioblastomas), kidneys, pancreas, adrenal glands, and others, of
cyst, solid, or mixed characteristics.
Method: The case history involves a female patient, 29 years old, who
was admitted to the Unidad Nacional de Psiquiatra with weight loss,
weeping, diagnosed with anorexia nervosa 4 years before, weight loss of
22 kg, nausea, vomit, feeling of difficulty swallowing and gastric repletion;
for the past 2 years symptoms are associated to feelings of depression, fits
of weeping, feelings of despair, social and labor deterioration, asthenia,
dry cough, and amenorrhea.
Results: While in this center, a lab test showed hyponatremia; abdominal
magnetic resonance revealed numerous images of liquid behavior of various sizes in cortex of both kidneys, heterogeneous behavior on the right
side. Retroperitoneal cyst images in pancreatic body and tail, also in psoas
muscle. Cranial magnetic resonance. showed space-occupying lesion
(SOL) beneath the fourth ventricle and behind the medulla oblongata,
heterogeneous solid anteroposterior component causing moderate
obstructive hydrocephalia.
Conclusion: Surgery to remove SOC. Died hours later.
References: 1- Richard E. Behrman, M.D, Robert m. Kliegman, M.D.,
Ann M. Arvin, M.D. Nelson Tratado de Pediatria 15a Ediccion Volumen II.
Junio 1997: 2124. 2- Van Der Hout, A.H: et al; The region of common al
elic losses in sporadic renal cell carcinoma is bordered by the foci D3s2
and thrb; Genomics Nov 1991. 11(3): 537-542. 3- Neumann HPH,
Wiestler OD. Clustering of features of von Hippel Lindau syndrome: evidence for a complex genetic locus. Lancet 1991:337:1052-1054.
4.- Maher ER, Yates JRW, Harries R, Benjamin C, Harris R, Moore AT,
Ferguson- Smith MA. Temporal Sequence. Q J Med 1990;77:51-63.
5.- PYKE, C.M. et al; The spectrum de Serous Cytoadeoma of the pancreas; clinical, pathologic and surgical aspects; ann. Surg. Feb1992;
215(5); 132-139. 6.- Glenn, E.M, et al; Screening for VHDL. By DNA polymorphism analisys; Jama March 1992. 4; 267 7.- Choyke, PL; Glenn,
G,; Walther, Me; Patronas, N; Von Hippel Lindau: Genetic, clinical and
imagin features. Radiology (march) 1995: 146 : 126-642RA. 8.- Melmon
KL, Rosen SW. Lindaus disease. Am J Med 1964;36:595-617.
P-08-05
QEEG cordance and LORETA changes as a predictor of
response to antidepressive treatment in patients with
resistant depressive disorder
Martin Brunovsky
Prague Psychiatric Center, Prague 8, Czech Republic
Martin Bares, Miloslav Kopecek, Tomas Novak, Pavla Stopkova, Vladimir Krajca
Introduction: A new quantitative EEG method - EEG cordance [1,2],
which combines complementary information from absolute and relative
power of EEG spectra, have shown sufficient capability to predict clinical
response in patients with unipolar depression. We examined whether this
new indicator represents a phenomenon associated with response to different antidepressive treatment in patients with resistant depressive disorder.
Method: The subjects were 25 inpatients (10 men, 15 women) with
treatment resistant depression. EEG data and response to treatment were
monitored at baseline and after 1 and 4 weeks on new antidepressant
treatment. QEEG cordance was computed at 3 frontal electrodes in theta
frequency band. The nonparametric statistical tests were used to perform
the within group (Wilcoxon Sign Rank Test) and between group
(Mann?Whitney U Test and Fisher Exact Test) analyses. Additionally we
performed brain electromagnetic tomography analysis (LORETA) [3] to
reveal which brain regions differ in their activity with respect to time-specific and response-specific changes.
Results: All 25 patients completed the 4-week study. All eight responders
showed decreases in prefrontal cordance after the first week of treat-
172
ment. The decrease of prefrontal QEEG cordance after week 1 in responders as well as the increase in nonresponders were both statistically significant and the changes of prefrontal cordance values were different
between both groups. LORETA analysis revealed an increase of excitatory
processes in the posterior cingulate and insula in the responder group,
whereas a decrease in the posterior cingulate and increase in the subgenual part of anterior cingulate was observed in non-responders after 1
week of treatment. An increase of inhibition in the rostral anterior cingulate in responders was seen after 4 week of treatment. The excitatory
processes were increased in widespread neocortical regions in responders,
whereas decrease in right parietal lobe was found in nonresponders.
Conclusion: Our results showed that significantly different time-specific
and response-specific changes in neuronal electrical activities exist after
week 1 and 4 of an antidepressant therapy. The decrease in prefrontal
EEG cordance may indicate early changes of prefrontal activity and can
become a useful tool in the prediction of response to antidepressants.
Work was supported by the project of the IGA MZCR No.1A8600.
References: 1.Leuchter AF, Cook IA, Lufkin RB et al. Neuroimage
1994;1:208-219. 2.Cook IA, Leuchter AF, Morgan M et al.
Neuropsychopharmacology 2002;27:120-131. 3.Pascual-Marqui RD,
Michel CM, Lehmann D. Int J Psychophysiol 1994;18:49-65.
P-08-06
The effects of emotion in facial cognition evaluated by
P300 and LORETA analyses compared between patients
with schizophrenia and healthy subjects
Yoshifumi Waseda
Neuropsychiatry, Kurume, Japan
Kiichro Morita, Toshimasa Matsuoka, Keiichiro Mori
Introduction: In this study, we analyzed the P300 component of the visual ERPs to evaluate the effects of an emotion in facial cognition between
schizophrenic patients and healthy controls, and also performed LORETA
analysis.
Method: Twelve schizophrenic patients diagnosed by ICD-10
(12 Paranoid and 6 non-paranoid) and age-sex matched 18 healthy subjects participated in this study. The visual induction-related potential was
measured using NeuroPack (Nihon Koden), and oddball tasks (target stimulation: crying or smiling baby face, non target stimulation: neutral baby
face) were used. EEG was recorded with 18 sites (F3, F4, C3, C4, P3, P4,
O1, O2, F7, F8, T3, T4, T5, T6, Fz, Cz, Pz, and Oz) according to the international 10/20 System. LORETA analysis was performed using the LORETA Explorer by the paired test between stimuli and the non-paired test
between groups (p<0.01). Positive and negative syndrome score (PANSS)
was used to evaluate the symptoms in patients. Ethics Committee of
Kurume University approved the present study. Written informed consent
was obtained from all subjects prior to study.
Results: The P300 amplitude for the crying baby face was significantly
larger than that for smiling baby face in healthy controls but there was no
significant differece in patients. When viewing the crying baby face, the
P300 amplitude in healthy controls was significantly larger than that in
patients, but no difference was observed in the P300 amplitude for the
smiling baby face between groups. LORETA analysis demonstrated that
there were significant differences of the activity in the Left 37, 39 areas
between the crying and smiling baby faces in healthy controls.
(Crying>smiling). LORETA analysis demonstrated that there were significant differences of the activity in the Right 4, 40 areas between the crying and smiling baby faces in patients. (Smiling > Crying)
Conclusion: Event-related potential and LORETA analyses can be used for
the psycho-physiological evaluation of cognitive dysfunction in schizophrenia, and it is important to diagnose such cognitive disorder secondarily and to determine the therapeutic strategy.
References: 1)Y. Shoji, K. Morita, M. Shigemori et al: Characteristics of
cognitive function in patients with higher brain dysfunction after brain
injury: an event-related potential study International Congress Series
1278 (2005): 352-355 2)K. Morita, H. Shoji, H. Yamamoto et al:
Characteristics of cognitive function in patients with Parkinsons disease:
a comparison with healthy subjects International Congress Series 1278
(2005): 344-347
P-08-07
Neuropsychiatric aspects in Huntingtons disease focused
on aggression
Markus Alexander Lindinger
Univ. Clinic of Psychiatry, Medical University Graz, Austria
Anna Hoedl, Helmut Schoeggl, Hans Peter Kapfhammer, Paphael Maria
Bonelli
Introduction: Aggression is one of the most frequent psychiatric symptoms in Huntingtons disease. The clinical observations showed an
increased aggressive behavior which comes with the progression of the illness. The increased aggression presents a big problem for the patients as
well as for their social environment. In this study we wanted to figure out
the occurrence of aggression in patients with Huntingtons disease.
Method: 41 patients (18 female and 23 male) in different stages (1 to 4)
with genetically diagnosed HD were examined for this study at the Dept.
of Psychiatry at the Medical University Graz. For the assessment of aggression, 4 standardized tests ( FAF, BDF , STAXI and AF SE) which describe a
total of 25 qualities of aggression were used. The period of illness was
operationalized by the illness stage, illness time, CAG-Repeats and the
UHDRS.
Results: High correlations between the aggression questionnaires and
the UHDRS subscale cognitive function were found. Especially for the
subscale reactive aggression (p=0.002), debt (p = 0.001), aggression
(p=0,004), anger state (p= 0.004) and the subscale sum of aggression
(p=0.019). Furthermore the aggression properties correlate significantly
with the subscale functional capacity, independence and psychosocial function of the UHDRS, with age, gender, illness stage, illness
duration and the CAG-Repeats .
Conclusion: Our results prove the clinical observation that increased
aggressive behavior depends on the period of illness. We can say that
UHDRS and its subscales show a good predictor for the development of
aggressive behavior in HD.
P-08-08
Efficacy of a program of mental health implemented during eight years on a 60 patients group with diagnosis of
schizophrenia
Martinez Psiquis
Argentina
Daniel Cosacow, Stella Maris di Cio, Fabianna Cabezaz, Jorge Galvan,
Dorotea Agote
Introduction: It is a follow-up during eight years of a 60 patients`s group
with diagnosis of Schizophrenia chosen at random, between those who
were under treatment in this Institution; making evaluations through the
evolution of the disease implementing therapeutic strategies from
Program of Mental Health. In order to measure the evolution and grade
of disease many indicators were chosen. This are: quality of life, psychiatric symptomatology, psychiatric hospitalization needs, treatment continuation, and suicides prevalence. This Mental Health`s Program was instrumented from 1.982 and allowed us: to reduce the rate of psychiatric
hospitalization, not only emergency but chronic, to reduce hospitalization
period, to reduce the incidence of suicides, to reduce general symptomatology of patient, to improve patients quality of life and to reduce the
incidence of all-cause discontinuations.
Method: A-Inclusion Criteria Schizophrenia, as defined in the DSM IV in
its different subtypes. B-Exclusion Criteria To have another associated psychiatric diagnosis C-Mental Health`s Program Criteria. 1. single psychiatric
controls. 2. single, groups and relative psychotherapies. 3. medication
group. 4. day hospitalization. 5. 24 hs. Psychiatric-psychological help.
6. 24 hs. domiciliary and institutional psychiatric emergency. 7. psyquiatric
hospitalization in crisis, emergency/chronic. 8. night hospitalization.
9. weekend hospitalization 10. different programs for patients under
observation and/ or in crisis. 11. Protected house. D- Psychiatric symptomatology`s evaluation.Positive and Negative Symptoms Scale from Drs.
Fiszbein, Kay and Opler. E-Quality of life`s evaluation. Quality of Life Scale
from Dres. Heinrichs, Carpenter and Naln, from the Psychiatric
Investigational Center (Marryland) was used; it contains 21 items in order
to examine functionality at the moment of scale`s application in non-hospitalized patients, independently of psychotic symptoms presence or
absence. It submits reliable information about symptomatology and functionality within the 4 previous weeks. Each item contains 7 values (lowest:0-1; highest: 5-6). Maximun score of normal function is
132. Items in this scale can be divided in four categories: Interpersonal
relationships. Instrumental role. Intrapsyquical bases Bases and activities.
Results: Will be exposed by using the statistical method showing each
examined item and exposing a comparison between them and
International bibliography used in this study.
Conclusion: Mental Health`s Program implemented in this group of
patients: to reduce the rate of psychiatric hospitalization, to reduce rate
of chronic hospitalization, to shorten hospitalization`s period, to reduce
rate suicides, to reduce patient`s general symptomatology, to improve
patients quality of life and to reduce the amount of treatment discontinuation.
P-08-09
Polyunsaturated fatty acids omega 3 and prostaglandins in
depression and schizophrenia
Iris Lieber
Argentina
Aaron Epelbaum
Introduction: Purpose: We consider that the intake of polyunsaturated
fatty acids, Pufa ,omega 3 can be useful as a coadjuvant to other neuropsychomolecules, for the prevention and treatment of depression and
schizophrenia. Considerations: It was found that there is an alteration in
the concentration of Pufa in the phospholipidic membrane and in the balance in between the different series of prostaglandins. Essential fatty
acids are fundamental constituents of the phospholipidic membrane, they
are precursors of prostaglandins, which belong to the family of
eicosanoids. Prostaglandins are tissue hormones, intracellular, local autacoids, autocrine and paracrine, they act as neuromodulators. They control the hormonal systems, vital functions like cardiovascular, inmunitary,
reproductive, and central nervous system. We point out that they also
participate in the psyconeuroinmunoendocrinologic system PNIE. An adequate equilibrium of the micro and macronutrients and of the ratio of
essential polyusaturated fatty acids Pufa omega 3 and omega 6, are
important to successful eicosanoid modulation. We describe the different
factors that can facilitate or interfere in the metabolic routes of the fatty
acids omega 6 and omega 3, until its transformation in prostaglandins.
Pufa are vulnerable to the presence of oxygen, they can form free radicals, which produce oxidative stress, accelerates the process of aging and
degenerative diseases. Rare fatty acids are produced in refined oil when it
is heated ,or partially hydrogenated they transform the fatty acids to the
trans series and they act as toxic and blocking agents in the normal formation of prostaglandins. Hibbeln, Pett, Maes, Stoll, Kalina, have found a
deficit of Pufa omega 3 in mayor depression and bipolar disorders, being
useful its administration as stabilizer of mood. Horrobin presented the
hypothesis of the membranes and neurodevelopment ,and sustains that
in schizophrenia there could be an unbalance of the different series of
prostaglandins, and that there is a reduction in the level of Pufa in the
serum and in the membranes of the red corpuscles in the schizophrenics.
We also treated patients with depression and schizophrenia with nutritional supplements with fatty acid omega 3.
Method: Group A: Patients with Depression: mild to moderate.
24 patients, ranging 30 to 65 years.18 female, 6 male. Group A l,
12 patients were given fatty acid omega 3, ( A1a and A1 b.) Group A 2,
12 were given placebo. From the group A l,a) six were given capsules that
contained EPA acid eicosapentaenoic acid, 300 mg ,in 1000 ml of fish oil,
2 capsules in each meal. A1 b) six patients received fatty acids omega 3,
600 mg in 1000 ml of Chia oil, l capsule in each meal. Group B: Patients
with Schizophrenia: 16 patients: 10 male, 6 female. Ages: 25-50 B1
8 patients were treated with essential fatty acid omega 3, 600 mg in each
meal, B2 8 patients with placebo.
Results: Evaluation was done with the Beck Scale for depression. The
response rates calculated in the Beck total score was found a mean 50 %
decrease from the baseline. We observed a reduction in the symptoms of
depression and a better quality of life without side effects.,compared ith
the group placebo. In the clinical assessments of patients with schizophrenia using the positive and negative syndrome scale PANSS.They were carried at baseline and after 2 and 4 months. There was a remission in the
173
symptoms, according to the mean Panss total score scale, that was not
found in the group placebo.
Conclusion: In our clinical investigations we obtained improvement in
the symptoms in patients with depression and schizophrenia with a nutritional supplement containing omega 3 polyunsaturated fatty acid given
alone or associated to the usual psychiatric medication, as adjuvant, without side effects and good tolerance. The purpose is to compensate the
deficiency of essential Pufa in the organism to obtain a balance of essential fatty acids and in the series of prostaglandins for a better health and
quality of life according to the principles of orthomolecular psychiatry.
References: Hibbeln J.R. Fish consumption and mayor depression.
Lancet :33 51:1213,1998 Horrobin:D.F. The membrane phospholipids
hypothesis as a biochemical basis for the neurodevelopmental hypothesis
of schizophrenia. Schizophr.Res. 3 0:193-208,1998 Lieber I.I. Epelbaum
A, Epelbaum C.A., Epelbaum D.M. Orthomolecular Psychiatry ,essential
fatty acids and prostaglandins: Argentine Journal of Biological
Psychiatry, Buenos Aires, Vol IX, 75, 19-31-2002. Lieber I.I. Epelbaum A,
Epelbaum C.A., Epelbaum D.M. Polyunsaturated fatty acids omega:
Deficit of fatty acids omega 3 in psychiatric disorders. Journal of Clinical
Neuropsychopharmacologoy: Vol X,Nro 72,12-31-2005. Lieber I.I.
Epelbaum A., Epelbaum C.A., Epelbaum D.M. Influence of polyunsaturated fatty acids and prostaglandins. Argentine Jounal of B iological
Psychiatry. Vol X,Nro 77,pag 1 7-21, 2003. Stoll A. Severus W.-E.,
Freeman M.P.,Rueter S. :Omega 3 fatty acids in bipolar disorder
Arch.Gen.Psychiatric, 56:407-412,1999.
P-08-10
Low resolution brain electromagnetic tomography
(LORETA) in patients with Huntingtons disease
Annamaria Painold
Medical University Graz, Psychiatry, Austria
Raphael Maria Bonelli, Peter Anderer, Anna Katharina Hoedl, Josef Diez,
Franz Reisecker, Hans Peter Kapfhammer, Bernd Saletu
Introduction: Huntingtons disease (HD), a progressive neurodegenerative
disorder, is characterized by a clinical triad of psychiatric, cognitive and
motor disturbances. Its core pathology involves degeneration of the basal
ganglia, in particular, the caudate and putamen. Patients with HD show
EEG maps that differ statistically from each other and from normal controls. This study is going to be performed in order to address the question
whether the newly introduced technique of 3-dimensional low-resolution
electromagnetic tomography (LORETA) is able to detect abnormalities in
patients with HD.
Method: We investigated vigilance-controlled resting EEGs of 95 patients
with HD of 20-69 years of age compared to 95 healthy age- and sexmatched controls. Furthermore the EEG results were correlated with the
results of the Hamilton Rating Scale for Depression, the Hamilton Anxiety
Scale, the PANSS und the Unified Huntingtons Disease Rating Scale
(UHDRS). Imaging of the regional brain electrical activity compared to the
group of healthy subjects by means of EEG tomography such as low-resolution electromagnetic tomography (LORETA) is going to be used for
identifying brain areas predominantly involved in our patients.
Results: The new method supposes that neighboring neuronal populations
are simultaneously and synchronously activated. The basic assumption is
based on evidence from single cell recordings in the brain that demonstrates
strong synchronization of adjacent neurons.
Conclusion: This is the largest EEG study on HD, and the first with LORETA.
P-08-11
The clock drawing test and its neuroanatomical correlates
in mild cognitive impairment and Alzheimers disease as
revealed by optimized voxel-based morphometry
Philipp Thomann
University of Heidelberg, Department of Psychiatry, Germany
Vasco dos Santos, Pablo Toro, Johannes Schrder, Marco Essig
Introduction: The Clock Drawing Test (CDT) is a widely used instrument
in the neuropsychological assessment of Alzheimers disease (AD). As CDT
performance necessitates several cognitive functions (e.g. visuospatial
and constructional abilities, executive functioning), an interaction of multiple brain regions is likely.
174
Method: 51 subjects with mild cognitive impairment, 23 with AD and

15 healthy controls underwent high-resolution magnetic resonance imaging. Optimized voxel-based morphometry (VBM) was performed to investigate the putative association between CDT performance and gray matter
(GM) density throughout the entire brain.
Results: In the first step of analysis (p<0.001, uncorrected), VBM revealed
a reduced GM density in numerous cortical (temporal lobe, frontal lobe,
cerebellum) and subcortical (thalamus, basal ganglia) brain regions to be
associated with poorer CDT performance. When corrected for multiple
comparisons over the whole brain (p<0.01), the associations remained
significant in the left temporal and - less pronounced - the right temporal
lobe.
Conclusion: VBM demonstrated an impaired CDT performance to be
significantly correlated with atrophic processes in multiple brain regions,
reflecting the fact that CDT performance requires an interaction of several cognitive domains. The observed structural alterations were pronounced in the temporal lobe, a region which is known to be affected
early in the course of AD.
P-08-12
Visual event related potentials in patients with autonomic
dominant spinocerebellar ataxia type 2
Ales Urban
University Medical School, Dept. of Psychiatry, Stara Boleslav, Czech
Republic
Jan Kremlaek, J. Masopust, Marin Valis
Introduction: The aim of the present study was to determine how cerebellar pathology can impact visual information processing. The primary
interest of our study was to explore whether there is a differential contribution of parvocellular and magnocellular system to the deficit of visual
processing in patients with spinocerebellar ataxia type 2 (SCA2).
According to literature data we expected normal function of parvocellular pathway and impairment in the magnocellular system function.
Method: We examined 8 patients (ages 25 - 72 years, mean 44.4 years; four
male) with genotypically confirmed SCA2. For the electrophysiological evaluation of the visual system function we used three types of stimuli: patternreversal (activating primary visual cortex), motion-onset(activating dorsal
stream and extrastriate areas) and direction discrimination task in odd-ball
paradigm (complex fronto-central activation). For statistical evaluation we
used dominant peak latencies and amplitudes for each stimulus and compared them with normal values.
Results: There was no statistically significant difference in P100.
Interestingly the late negative peak (N145) in the pattern reversal
response had prolonged latency and reduced amplitude. The motiononset dominant-peak (N160) had prolonged latency and reduced amplitude in SCA2 group. Similar changes likewise in N145 and N160 were
present in N2 wave of the odd-ball response. In our patient group we
observed also the P300 latency shift together with amplitude reduction.
The reaction time was slower as well. The comparison between group of
SCA patients and normal data exhibited significant differences in dorsal
stream processing.
Conclusion: These preliminary data support the notion that cerebellum
can play a role in visual information processing. Our results show a deficit
particularly in motion perception. It might be possible that processing in
the dorsal pathway is affected by cerebellar dysfunction. It is unclear
whether the deficit in magnocellular system is specific for cerebellum or
if it is marker of general vulnerability. The work was supported by Czech
fund VZ MSM 0021620816.
References: Abele M, Burk K, Andres F, Topka H, Laccone F, Bosch T,
Brice A, Cancel G, Dichgans J, Klockgether T. Autosomal dominant cerebellar ataxia type I Nerve conduction and evoked potential studies in families with SCA1, SCA2 and SCA3. Brain 1997; 120: 2141-2148. Jokisch D,
Troje NF, Koch B, Schwarz M, Daum I. Differential involvement of the cerebellum in biological and coherent motion perception. European Journal of
Neuroscience 2005; 21: 3439-3446.
P-08-13
How genes modulate reward processing and the relationship to sensation seeking
Juliana Yacubian
Hamburg, Germany
Tobias Sommer, Katrin Schroeder, Jan Glaescher, Raffael Kalische, Dieter
F. Braus, Boris Leuenberger, Christian Bchel
Introduction: Motivational and reward related functions depend on phasic
dopaminergic neurotransmission from the midbrain to the ventral striatum which is modulated by reuptake through the dopamine transporter
(DAT) and degradation through Catechol-O-Methyltransferase (COMT).
Genetic variations of both proteins have repeatedly been linked to novelty
seeking and neuropsychiatric diseases.
Method: To understand how genetic variation of these genes influences
the dopaminergic system, we evaluated 105 volunteers using fMRI and
a guessing task that is sensitive to ventral striatal activation during reward
anticipation. Each trial began with the presentation of the backside of
eight playing cards. Volunteers had to place a given amount of money
(EUR 1.00 or EUR 5.00) on individual playing cards, allowing for the control of reward magnitude. In some trials, the bet had to be placed on the
corners of four adjacent cards and in others only on single cards, which
allowed for the control of reward probability. Sensation seeking was
assessed using Zuckermans Sensation-Seeking Scale (Form V). For the
dopamine transporter 44bp VNTR and COMT polymorphisms the samples
were amplified by PCR and analysed using forward and reverse primers.
Seven volunteers were excluded from the sample due to a positive urine
drug screen.
Results: We show that ventral striatal function was modulated by an
epistatic gene-gene interaction between COMT and DAT: Although most
genotype combinations exhibited the expected activity increase in the
ventral striatum with more likely and larger rewards, two COMT-DAT
genotype combinations predicting either extremely low or high phasic
dopamine neurotransmission showed a decrease of ventral striatal activity
and thus rendered the relationship between neural activity and predicted
phasic DA non-linear (i.e. inverted u-shape). Our data shows that this
inverted u-shape can simply emerge from an epistatic gene-gene interaction between two dopamine regulating genes. Importantly, this response
pattern was behaviourally relevant as it was paralleled by increased sensation seeking.
Conclusion: Our approach shows the strengths of combining imaging
with genetics in explaining more complex behavioural traits with a genegene interactions. We expect this to be a starting point for revisiting the
genetic basis of polygenic personality traits and psychiatric disorders with
emphasis on gene-gene interactions. In particular, the observed link
between DA regulating genes, sensation seeking and ventral striatal
responsiveness might be relevant for addiction research, because higher
levels of sensation seeking and decreased responsiveness of the mesolimbic reward system are a hallmark of addiction.
P-08-14
Gender differences in pharmacotherapy response to SSRIs
among a group of Latino children
Nikaury Rivera-Antongiorgi
UPR - School of Medicine, Dept. of Psychiatry, San Juan, Puerto Rico
Introduction: Anxiety disorders affect as many as 20% of children and
adolescents (American Academy of Child and Adolescent Psychiatry,
1997). Childhood onset anxiety and depressive disorders cause significant
psychosocial and work impairment during adulthood (Otto et al, 2001;
Pine et al, 1998), indicating the need for early and efficacious treatment.
Selective serotonin reuptake inhibitors (SSRIs) are part of the pharmacotherapy used to treat anxiety disorders but few, if any, studies have
been done to correlate response to treatment and gender differences
between children taking SSRIs or combined therapies. Of children with
anxiety disorders, at least 60% suffer from 2 anxiety disorders and 30%
suffer from 3 disorders (Clark et al 1994, RUPP Anxiety Study Group,
2001).
Method: The goal is to establish a population profile by reviewing the
medical history on record for children age 11 and under (to eliminate the
effect of hormonal changes during puberty), treated with SSRI alone or in
combination with other medications, at the Child & Adolescent Mental

Health Clinic in the Antonio Ortiz Pediatric Hospital. The variables pertinent to our study are the following: - Age -Gender Diagnosis (DSM-IV including comorbid diagnosis) -Severity of illness
(# of symptoms present) and GAF (global assessment of functioning)
 - Age at time of diagnosis -Pharmacotherapy (simple or combined, fixed or flexible dosage, frequency and duration) Psychosocial Therapy Modalities (ex. Cognitive Behavioral Therapy) Response to treatment (based on # symptoms, GAF, and parent/teacher
observations) -Family history of mental illness (including pre-natal or
post-natal exposure through breastfeeding to SSRI) -Socio-economic
level Working Hypothesis: We hypothesized that there are genderspecific differences in diagnosis of anxiety disorders and subtype combinations present (ex. generalized anxiety disorder with co-existing separation anxiety disorder being more common in females and social phobia
with OCD being more common in males). We also expect gender-specific
differences in response to pharmacotherapy (SSRI versus SSRIs + benzodiazepine)
P-15
Neuroimaging II
T10 Neuroimaging
P-15-01
123-i-adam-spect imaging of serotonin transporters in
depressed patients-impact of gender to the relationship
between sert and psychopathological symptoms
Konrad Uebelhack
Charite University Medicine, Department of Psychiatry, Berlin, Germany
Leonora Franke, Natalie Herold, Michail Plotkin, Holger Amthauer, Ralf
Uebelhack
Introduction: In patients suffering from major depression, the availability
of serotonin transporters (SERT) for the binding of SPECT and PET radioligands has been found to be either decreased, increased or unchanged
depending on the brain region investigated, the radiotracer and the study
methodology. The objective of this study was to determine whether characteristics of [123I]-ADAM binding in the midbrain and frontal lobe are
related to different aspects of major depression in the whole group of
patients as well as in males and females separately.
Method: SPECT scans were performed on 32 non-medicated patients
suffering from major depression (14 females and 18 males) after administration of 165-200 MBq [123I]-ADAM. The [123I]-ADAM binding was
assessed 4h after injection using MR-guided regions-of-interest placed in
the midbrain, frontal lobe and cerebellum. The ratios of activities
measured in the midbrain or frontal lobe to those in the reference region,
the cerebellum, (Quomid and Quofro) were calculated and correlated
with the severity of depression as expressed in the HAMD-17 total scores
or with the items of the scale. The effect on these correlations of confounding factors such as age, gender, and activity measured in the cerebellum was analyzed.
Results: There were no significant correlations between HAMD total
score and the ratios Quomid or Quofro, nether in the whole group nor
in males or females separately. However, gender differences in significant
relations between the HAMD items (item 5,6,9,12, and 17) and the
indices of [123I]-ADAM binding were observed. The findings were influenced by the activity measured in the cerebellum, a region which represents per definition the nonspecific binding of the tracer.
Conclusion: The SERT in the midbrain and frontal lobe seems to contribute differently to the severity of several symptoms in depressed males
and females. In the interpretation of these findings, methodical difficulties with the SPECT data should be take into account.
175
P-15-02
Influence of gender on serotonin-1a receptor distribution
in the hypothalamus
Ulrike Moser
Medical University of Vienna, Dep. of General Psychiatry, Austria
R. Lanzenberger, C. Spindelegger, W. Wadsak, M. Mitterhauser, P. Stein,
A. Holik, L. Mien, K. Kletter, S. Kasper
Introduction: Studies in animals have shown that serotonin-1A receptor
(5-HT1A) agonists stimulate the hypothalamic-pituitary-adrenal (HPA) and
the hypothalamic-pituitary-gonadal axis (HPG). Alterations in these hormonal systems as well as decreased 5-HT1A receptor levels were reported
in affective disorders [1]. Depression and some anxiety disorders are much
more common in women. The aim of this PET study was to investigate
gender differences in the hypothalamic 5-HT1A receptor binding potential (RBP).
Methods: 18 healthy males and 18 matched healthy females participated
in this PET study. Dynamic scans were acquired after bolus injection of
[carbonyl-11C]WAY-100635. A series of 30 time frames during 90 minutes was collected. 35 contiguous slices (FWHM = 4.36mm) were reconstructed. Two regions of interest (ROI) were drawn on co-registered
structural MR images (hypothalamus, cerebellum). For quantification of 5HT1A RBP we used the Simplified Reference Tissue Model (SRTM) implemented in PMOD 2.7. An univariate ANOVA with hypothalamic 5-HT1A
RBP as dependent variable, group (females versus males) as fixed factor,
and age, ROI-size and radiochemical variables as covariates was
performed.
Results: The hypothalamic 5-HT1A RBP was 0.810.33 (mean SD) in
females and 1.090.38 in males. The 5-HT1A BP was significantly lower
in females compared to males (-24,8%, p=0.035, ANOVA).
Conclusion: 1) Our results show a sexual dimorphism of the 5-HT1A distribution in the hypothalamus which indicates that sex hormones might
have a regulatory effect on the 5-HT1A distribution consistent to findings
in animals [2]. 2) Gender-related differences in the HPA- and HPG-axis
might be modulated by the 5-HT1A receptor. 3) The 5-HT1A receptor
might be involved in gender-specific differences in the prevalence of
depression, as well as some anxiety disorders.
References: 1. Lanzenberger R, et al. Reduced serotonin-1A receptor binding in social anxiety disorder. Biol Psychiatry, 2006. in press2. Bethea CL,
et al. Diverse actions of ovarian steroids in the serotonin neural system.
Front Neuroendocrinol, 2002. 23(1): p. 41-100
P-15-03
Neuroanatomical basis of behavioural disturbances inpatients with prefrontal lesions
Andrea Slachevsky
U. de Chile, Facultad de Medicina, Santiago, Chile
Carolina Perez, Gonzalo Rojas, Patricia Alegria, Eduardo Bravo, Marcela
Pena
Introduction: The study of patients with prefrontal lesions suggested
that neuropsychological and behavioural evaluations reflect different
aspects of the organization of mind in prefrontal patients. The functional
relationship between cognitive and behavioural abilities and the anatomical correlates subserving them still remain unclear, partly because of the
lack of standard behavioural tests and the scarce number of multiple-case
reports. The recent development of structured questionnaires has allowed
a more reliable assessment of patients with prefrontal lobe lesions, thus
improving the identification and quantification of dysexecutive symptoms
in every day life. However, to the best of our knowledge, no previous multiple-case studies using structured questionnaires to explore deficiencies
in daily life in patients with lesions restricted to the prefrontal cortex have
been reported. In addition, significant advances in neuroimaging techniques allow a more reliable characterization of focal cerebral lesions.
Method: We studied 34 patients with prefrontal lesions and 40 healthy
controls. The neuropsychological assessment included the: a) Frontal
Assessment Battery; b) Modified Version of the Wisconsin Card Sorting
test; c) Verbal fluency; d) Graphic series and e) Frontal behavior.
Behavioural abilities of patients were assessed with the: i) Dysexecutive
questionnaire and ii) Inventaire du Syndrome Dysexecutif
176
Comportemental. All patients received a 3D-MRI

Results: Our results showed that patients with simultaneous lesions in
supero and infero medial areas of the prefrontal cortex exhibited higher
behavioral disturbances. Bilateral lesions were also associated to greater
behavioral troubles. On the contrary, cognitive abilities were globally
impaired in prefrontal patients
Conclusion: Our results suggested that troubles in behaviour were not
related to cognitive troubles. Results were discussed in relation to current
models of the organization of the prefrontal cortex and its role on behavior control.
P-15-04
BDNF Val66Met polymorphism and hippocampal volume in
elderly bipolar patients
Stevin Zung
University of Sao Paulo, School of Medicine, Brazil
Quirino Cordeiro, Fabio Duran, Geraldo Busatto, Homero Vallada
Introduction: The Val66Met polymorphism of the BDNF gene is associated with susceptibility to bipolar disorder and also with variations of hippocampal volume in healthy subjects. The present study investigated
whether this polymorphism was associated with hippocampal volume in
elderly bipolar patients.
Method: Magnetic resonance imaging data were obtained in 49 bipolar
patients aged 60 years or older. Patients were divided in two groups: Val
homozygotes (n=28) and Met homozygotes or heterozygotes (n=21). The
volume of hippocampus was measured and compared between the
groups using voxel-based morphometry (VBM) based upon the Statistical
Parametric Mapping (SPM) technique. The voxels mapped to hippocampus were circumscribed using the small volume correction tool available in the SPM and differences were reported as significant if surviving
family-wise error (FWE) correction for multiple comparisons (p < 0.05).
Results: There was no difference on hippocampal volume between elderly bipolar patients with Val/Val genotype and those with Met alleles.
Conclusion: The volume of hippocampus was not associated with the
BDNF Val66Met polymorphism in our sample of bipolar patients. Studies
with larger samples are required to investigate the possible association
between BDNF Val66Met polymorphism and hippocampal volume.
References: 1- LU B, GOTTSCHALK W. Modulation of hippocampal
synaptic transmission and plasticity by neurotrophins. Prog. Brain Res.
200; 128: 231-241. 2- HARIRI AR et al. Brain-derived neurotrophic factor
val66met polymorphism affects human memory-related hippocampal
activity and predicts memory performance. J Neurosci. 2003; 23: 66906694. 3- SZESZKO PR et al. Brain-derived neurotrophic factor val66met
polymorphism and volume of the hippocampal formation. Mol Psychiatry
2005; 10: 631-636. 4- BUELLER JA et al. val66met allele is associated with
reduced hippoacampal volume in healthy subjects. Biol Psychiatry 2006;
59: 812-815. 5- RASMUSSON AM, SHI L, DUMAN R. Downregulation of
BDNF mRNA in the hippocampal dentate gyrus after re-exposure to cues
previously associated with footshock. Neuropsychopharmacology 2002;
27: 133-142. 6- DUMAN RS. Novel therapeutic approach beyond the
serotonin receptor. Biol Psychiatry 1998; 44: 324-335.
P-15-05
Effects of diazepam on the neuronal response to facial
expressions: A fMRI study
Cristina Del-Ben
FMRP-USP, Division of Psychiatry, Ribeirao Preto, Brazil
Cesar Ferreira, Tiago Sanches, Wolme Alves-Neto, Vinicius Guapo,
Draulio Araujo, Frederico Graeff
Introduction: Abnormalities in fundamental processes underlying the
brains response to environmental threats have been implicated in the
neurobiology of anxiety disorders (Deakin, 1998). The anxiolytic activity of
the benzodiazepines is well established. The aim of this study was to
verify the effects of the diazepam on the modulation of facial emotion
processing using blood oxygen level dependent (BOLD) fMRI.
Method: Nine healthy males volunteers completed two fMRI scanning
sessions each, separated by at least 2 weeks, in a randomised, balanced
order, double-blind design. Images were acquired on a Siemens
Magnetom Vision 1.5 T scanner using single shot echo planar sequences.
An oral dose of diazepam 10 mg or placebo was given 60 minutes before
the scanning. In a blocked design task, subjects were presented with pictures of neutral (A) and aversive (B) (angry, disgusted and fearful) faces
from the Pictures of Facial Affect Series (Ekman and Friesen 1976). The
blocks lasted 30 seconds in an ABABABABA design for each aversive
emotion. Whole-brain images were acquired over 4.5 minutes for each
emotion, in a randomized order. Subjects were asked to identify the gender of the faces not to describe or focus on the emotion pictured. Data
were analysed using BrainVoyager tm (version QX) with a general linear
model and normalized to Talairach space. Group comparisons (multystudy) have been done using a fixed effects analyses.
Results: Preliminary results have shown that, in comparison to neutral
faces, aversive faces enhanced haemodynamic activation in bilateral
amygdala, inferior frontal gyrus (Brodmann area = 46), superior temporal
gyrus (Brodmann area = 22) and fusiform gyrus. Diazepam increased the
activation in amygdala, thalamus and inferior frontal gyrus, bilaterally,
whereas attenuated the neuronal response in the right caudate and right
globus pallidus to aversive faces.
Conclusion: These results suggest that diazepam critically modulates incidental responses to emotional stimuli at a neural level. This could have
implications for our understanding of the neurocircuitary involved in normal and pathological anxiety
References: Deakin JF (1998) The role of serotonin in panic, anxiety and
depression. Int Clin Psychopharmacol;13 Suppl 4:S1-5. Ekman P, Friesen
WV (1976) Pictures of facial affect. Palo Alto: Consulting Psychologists.
P-15-06
White matter and ultrastructural changes in attention
deficit hyperactivity disorder: A Diffusion Tensor Imaging
(DTI) study in adult patients
Thomas F. Dielentheis
Psychiatrische Universittsklinik Mainz, Germany
D. El Masri, G. Vucurevic, M. Mazanek, M. Bayerl, T. Gesierich,
P. Stoeter, L.G. Schmidt
Introduction: Structural and functional neuroimaging studies of subjects
with Attention Deficit Hyperactivity Disorder (ADHD) demonstrated
abnormalities of the frontal-striatal circuitry as well as of other cortical
regions and the cerebellum. Most structural studies have been conducted
in children. The aim of this study was to investigate possible changes of
white matter in adult subjects with ADHD.
Method: 20 (11male, 9 female) ADHD patients and 20 age- and gendermatched healthy controls (age 19-51 years) underwent comprehensive
neuropsychological investigations as well as conventional and DTI scans.
MRI was performed with a 1,5 Tesla MR imager (Vision, Siemens,
Germany). Mean diffusivity (MD) and fractional anisotropy (FA) were
measured in 24 regions of interest (ROIs), e.g. in frontal, parietal, temporal,
cerebellar regions of the brain. For group comparisons, we computed
nonparametric Mann-Whitney U tests. For bivariate correlations, we used
Spearmans rank correlation test.
Results: ADHD patients showed higher diffusivity in the left frontobasal
region; in addition, there was a trend for a higher diffusivity in the right
caudate. Patients showed reduced anisotropy in the left temporal and as trend - in the left frontobasal white matter. Diffusivity and anisotropy
in these regions were correlated with ADHD parameters (WURS, TOVA),
but not with other neuropsychological parameters (e.g. intelligence).
Conclusion: Frontal and temporal ultrastructural and white matter

changes were found in adult ADHD patients and were associated with
test- and neuropsychological parameters of ADHD. These results confirm
frontal dysfunction found in many structural and functional studies in
ADHD patients.
P-15-07
Association between working memory dysfunction and
structural atrophy in schizophrenia
Paik In-Ho
Kangnam St. Marys Hosp, Psychiatry, Seoul, Republic of Korea
Hyun-Kook Lim, Seung-Kyu Bang, Chul Lee, Chang-Uk Lee
Introduction: The inferior frontal cortex and parietal cortex are important in performing working memory tasks. In this study we performed
fMRI studies to compare the activation regions between the schizophrenic
patients and normal controls. Gray matter (GM) loss between these two
groups was compared using the voxel based morphometry (VBM) analysis.
The brain regions showing differences in fMRI and VBM studies were
compared to investigate the consequence of structural atrophy on functional activation.
Method: This study included 14 schizophrenic patients (27.8 7.3y, M/F:
8/6) and 10 normal controls (22.0 6.6y, M/F: 8/2). The fMRI employed
an echo planar imaging (EPI) sequence using a 2-back WM test with
Korean Alphabet (KA). The VBM analysis was performed using the
AnCova model with sex, age, disease onset age, duration and MMSE.
Results: The working memory of schizophrenic patients was significantly
impaired comp! ared to controls. In fMRI schizophrenic patients showed
decreased activity in middle frontal and superior temporal, insula, caudate, hippocampus, parahippocampal gyrus, and fusiform gyrus compared to controls. On the other hand, the patient group showed
increased activity in the inferior frontal and inferior parietal brain. The
VBM results showed GM reductions in Schizophrenic patients in the middle frontal, medial frontal, inferior frontal, inferior parietal, middle temporal, superior temporal brain, and parahippocampal gyrus, lingual,
fusiform gyrus.
Conclusion: The WM impairment was related to the differences in functional activation in fMRI studies, and was associated with structural differences in the VBM analysis. The fMRI reveals that the parietal lobe and
inferior frontal show elevated activation in patients, and interestingly
these regions show corresponding GM loss in VBM analysis. The results
suggest that in order to perform the working memory task, a higher neuronal activity is needed to compensate for the volumetric loss
References: Petrides, M., Alivisatos, B., Meyer, E., Evans, A.C., 1993.
Functional activation of the human prefrontal cortex during the performance of verbal working memory tasks. Proc. Natl. Acad. Sci. 90, 878-882.
Shenton, M.E., Dickey, C.C., Frumin, M., McCarley, R.W., 2001. A review
of MRI findings in schizophrenia. Schizophr. Res. 49 (12), 1-52. Suzuki,
M., Nohara, S., Hagino, H., Kurokawa, K., et al., 2002. Regional changes
in brain gray and white matter in patients with schizophrenia demonstrated with voxel-based analysis of MRI. Schizophr. Res. 55 (12),41- 54.
P-15-08
Cortisole modulates task performance in emotion discrimination during fMRI scanning
Alexander Holik
Rupert Lanzenberger, Christian Windischberger, Christoph Spindelegger,
Susanne Friedreich, Patrycja Stein, Ulrike Moser, Siegfried Kasper
Introduction: The application of functional magnetic resonance imaging
(fMRI) in pharmacological drug research is limited by the fact that the
BOLD signal is an indirect haemodynamic measure of neural activity. As
such, test-retest reproducibility is rather low compared to other brain
mapping methods [1]. Here we investigated the relationship between cortisole and the performance in a frequently used emotion paradigm [2]
during fMRI scanning. Cortisole and its metabolites strongly modulate the
activation in limbic areas by activation of glucocorticoid receptors and
neurosteroidal effects such as GABA antagonism [3].
177
Method: 15 male and 18 matched female healthy subjects (28.17.0

and 23.72.4 yrs) performed both an emotion discrimination task (EDT)
and a cognitive task (Tower of London) during a single fMRI scanning
session at 3T. Blood samples were obtained during pre-examination at
least one week prior to fMRI-scanning at 8 am 1h to quantify basal cortisole levels.
Results: Error rates during EDT and TOL tasks were significantly higher in
females (0.100.05 vs. 0.050.04, p=0.004 and 0.230.14 vs.
0.130.10, p=0.018, ANOVA). Both error-rate (r=-0.75, p=0.001,
Pearsons` correlation) and performance (r=0.72, p=0.003) correlated significantly with cortisole plasma levels in males but not in females. No significant correlations were found in the cognitive paradigm.
Conclusion: The task-specific effects of cortisole do not indicate a significant inhibitory neurosteroidal effect of cortisole. Given the several times
lower frontal level of the mineralocorticoid receptor (MR) in men [4], the
gender-differences in performance might be modulated by MR binding
cortisole with high-affinity. The highly significant correlation between cortisole and performance supports the inclusion of the cortisole plasma level
as covariate in fMRI group analyses using emotion paradigms.
References: 1. McGonigle DJ et al. (2000). Neuroimaging 11: 708-34 2.
Fisher PM et al. (2006). Nat Neurosci 9: 1362-3. 3. Birzniece V et al.
(2006). Brain Res Rev 51: 212-39. 4. Watzka M et al. (2000). Steroids 65:
895-901.
P-15-09
Decreased brain activation in healthy subjects after
clomipramine treatment: An fMRI study during presentation of fear-provoking and neutral images
Jorge R. C. Almeida
University of Pittsburgh, Department of Psychiatry, USA
Carlos T. Cerqueira, Mary L. Phillips, Hermano Tavares, Edson Amaro Jr.,
Clarice Gorenstein, Valentim Gentil Filho, Geraldo Busatto
Introduction: Pharmacological functional magnetic resonance imaging
(fMRI) allows in vivo and non invasive mapping of the effects of centrally
acting compounds in the human brain. Antidepressant agents increment
serotonin and norepinephrine transmission in the brain, but there is not
yet a clear understanding about the pharmacodynamic effects of these
drugs in specific brain systems relevant to emotional processing. In order
to investigate this without the confounding influence of features of psychiatric disorders, we have treated healthy volunteers with an antidepressant agent and acquired fMRI data during presentation of emotion-provoking and neutral stimuli.
Method: Fifteen healthy volunteers were evaluated with fMRI after
receiving low doses of clomipramine for four weeks (time 1) and once
again after four weeks of washout (time 2). Fearful and neutral pictures
from the International Affective Picture System were used as stimuli.
Statistical parametric mapping was employed to analyze the fMRI data
(p<0.05, corrected for multiple comparisons).
Results: Relative to the unmedicated state, performance of the paradigm
in the medicated state was associated with decreased activation of the
right inferior frontal cortex during presentation of fearful stimuli. Also,
there was reduced activation of the left anterior cingulate gyrus during
presentation of neutral stimuli in the medicated state.
Conclusion: The above results are consistent with previous studies
reporting decreased activation of fronto-limbic/paralimbic regions implicated in emotion processing after use of antidepressants. Our findings
also suggest that this may occur not only during presentation of emotionprovoking stimuli, but also in response to neutral stimuli (which, when
contrasted with fear-provoking images, may be seen as positive stimuli).
resonance spectroscopy study (1). With SPECT, an increased striatal

dopamine transporter (DAT) availability has been described in ADHD (2,3);
in this study we looked for differences in the ratio of DAT availability of
the right and left caudate nucleus and the putamen of adult patients with
combined type of ADHD and with the purely inattentive type.
Method: DAT availability was measured by [Tc-99m]TRODAT-1 SPECT in
caudate nucleus and putamen in 20 adult patients with ADHD of inattentive type and in 21 adults with the combined type of ADHD, according to
the DSM IV criteria. For each patient the ratio of pixel per count in the
caudate nucleus and the putamen (CP ratio) was calculated for the right
and the left side. The two groups of patients were compared for possible
differences using t-test.
Results: Mean s.d. for CP ratio was 1.06 0.05 for the right side in the
inattentive group and 1.07 0.05 in the combined group (p = 0.30 in
t test, not significant); for the left side CP ratio was 1.04 0.06 in the inattentive and 1.05 0.05 in the combined group (p = 0.17, not significant).
Conclusion: No differences in the ratio of DAT availability in the caudate
nucleus and putamen could be found between adult patients with ADHD
of combined and inattentive type. Looking at the dopaminergic system,
both parts of striatum seem to contribute in a similar extent to symptoms
of attention deficit and hyperactivity/impulsivity in patients with ADHD.
References: 1. Hesslinger B et al. Neurosci Lett 2001; 304: 117-119 2.
Dougherty DD et al. Lancet 1999; 354: 2132-2133 3. Krause KH et al.
Neurosci Lett 2000; 285: 107-110
P-15-11
Decreased activation on cingulate gyrus to neutral stimuli
in health controls after four weeks of clomipramine treatment
Jorge Almeida
Sao Paulo, Brazil
Carlos Cerqueira, Mary Phillips, Hermano Tavares, Edson Amaro, Clarice
Gorenstein, Valentim Gentil, Geraldo Busatto
Introduction: Pharmacological functional magnetic resonance (fMRI)
allows in vivo and non invasive mapping effects of centrally compounds
in human brain. Antidepressants increase serotonin and norepenephrine
in the brain are effective in depression and anxiety treatment, but there is
no clear understanding so far in the pharmacodynamic effects in specific
brain systems without abnormalities of psychiatric disorders. The aim of
this study is identify the brain activity in healthy volunteers during emotional task performance and the relation with antidepressant treatment.
Method: Fifteen health volunteers were evaluated with fMRI after receiving low dose clomipramine for four weeks (time 1) and after four weeks
of washout (time 2). Fearful and neutral pictures were used as stimuli during the fMRI task. Statistical parametric mapping was used to examine
the fMRI data (p<0.05, corrected).
Results: Medicated subjects showed decreased activation in left anterior
cingulate gyri (t=4.69) to neutral stimuli ( see figure 1). Decreased activation in right inferior frontal (t=5.56) was found to fearful stimuli in the
medicated state.
P-15-10
Dopamine transporter availability of putamen and caudate
nucleus in adult patients with combined and with inattentive type of ADHD
Klaus-Henning Krause
Universitt Munich, Friedrich Baur Institut, Mnchen, Germany
Stefan Dresel, Christian LaFougere, Johanna Krause
Introduction: Adult patients with the inattentive and the combined type
of ADHD differed in the left striatum in a short echo time (1)H-magnetic
178
Conclusion: Our findings are consistent with previous literature reporting

decrease activation in subcortical limbic regions implicated in emotion
processing after use of antidepressants, and suggest that this may also
occur to neutral stimuli rather then fearful stimuli. Contrasted with the
fear stimuli, the neutral condition might be seen as a positive stimulus.
The serotonin role in the process of fearful and happy stimuli has been
shown an increased recognition of these conditions.
References: GORENSTEIN, C., GENTIL, V., MELO, M., LOTUFO-NETO, F. &
LAURIANO, V. (1998) Mood improvement in normal volunteers. J
Psychopharmacol, 12, 246-51. HARMER, C. J., BHAGWAGAR, Z., PERRETT, D. I., VOLLM, B. A., COWEN, P. J. & GOODWIN, G. M. (2003) Acute
SSRI administration affects the processing of social cues in healthy volunteers. Neuropsychopharmacology, 28, 148-52. HARMER, C. J., SHELLEY,
N. C., COWEN, P. J. & GOODWIN, G. M. (2004) Increased positive versus
negative affective perception and memory in healthy volunteers following
selective serotonin and norepinephrine reuptake inhibition. Am J
Psychiatry, 161, 1256-63.
P-15-12
Volume preservation of limbic and paralimbic structures in
aging during adult life: A voxel-based morphometry study
Debora Terribilli
Clinics Hospital, Psychiatry Institute, Sao Paulo, Brazil
Introduction: Previous morphometric MRI studies of elderly individuals
have shown accelerated gray matter (GM) loss with aging involving neocortical regions, but preservation of limbic/paralimbic structures1. We
wished to investigate the relationship between GM volumes and age in a
non-elderly adult population.
Method: A total of 91 healthy individuals (aged 18-50 years,
41 females/50 males), recruited in a circumscribed region of Sao Paulo,
Brazil, were investigated with morphometric MRI. The presence of significant linear correlations between GM volumes and age were investigated
using voxel-based morphometry.
Results: There were significant negative correlations between GM volumes and age across the entire brain. However, when regional GM analyses were performed using the total amount of GM in the brain as a confounding covariate, clusters of significant regional GM preservation were
found in limbic and paralimbic structures, involving the entire cingulate
gyrus and areas of the hippocampus, insula and amygdala (Z>3.09,
p<0.001).
Conclusion: Our results reinforce the notion that non-limbic structures
are more vulnerable to age-related morphometric changes in the human
brain, and indicate that divergent patterns of GM loss between
limbic/paralimbic and neocortical regions are already evident during nonelderly adult life. Such findings may be relevant to the understanding of
adult-onset neuropsychiatric disorders that supposedly involve abnormalities of cortico-limbic connections. Our results also warrant caution in the
interpretation of findings of case-control morphometric MRI studies in
which longitudinal designs are used, with repeated measures separated
by years.
References: Grieve SM, Clark CR, Williams LM, Peduto AJ, Gordon E.
Preservation of limbic and paralimbic structures in aging. Hum Brain
Mapp. 2005 Aug;25(4):391-401. Good CD, Johnsrude IS, Ashburner J,
Henson RN, Friston KJ, Frackowiak RS. A voxel-based morphometric
study of ageing in 465 normal adult human brains. Neuroimage. 2001
Jul;14(1 Pt 1):21-36.
P-15-13
Reduced glutamatergic signals in adult patients with
ADHD - a controlled magnet resonance spectroscopic study
Evgeniy Perlov
University Clinic Freiburg, Psychiatry and Psychotherapy, Germany
Alexandra Philipsen, Bernd Hesslinger, Martin Buechert, Johannes
Ahrendts, Bernd Feige, Emanuel Bubl, Jurgen Henning, Dieter Ebert,
Ludger Tebartz van Elst
Introduction: The dopaminergic system is thought to be essentially
involved in the pathogenesis of attention deficit/hyperactivity disorder
(ADHD). However, there is also evidence for abnormalities in the glutamatergic system and recent theories focus on a disturbed interaction
between the two systems as the essential pathogenetic mechanism of
ADHD. In the present study we wanted to test the hypothesis that prefrontal glutamate signals indirectly indicate dopaminergic dysfunction in
adult patients with ADHD.
Method: Twenty eight adult patients with ADHD and 28 group-matched
controls were studied using chemical-shift MR spectroscopy (TR = 1670 ms,
TE = 3.9 ms) of the prefrontal cortex covering the anterior cingulate gyrus
at 1,5 T hole body system (Magnetom Sonata, Siemens). The acquired
data was analyzed using Lc-Model software.
Results: A significant reduction of the combined glutamate /glutaminesignal in the right anterior cingulate cortex in patients with ADHD was
found (1.680.5 vs 1.930.5; t=0.8, df=61, p=0.05).
Conclusion: Glutamatergic alterations as measured with MRS might play
a role in the pathogenesis of adult patients with ADHD.
References: Carlsson, A., Hansson, L. O., Waters, N., & Carlsson, M. L.
1999, A glutamatergic deficiency model of schizophrenia, Br. J.
Psychiatry Suppl no. 37, pp. 2-6. Carrey, N., MacMaster, F. P., Sparkes, S.
J., Khan, S. C., & Kusumakar, V. 2002, Glutamatergic changes with
treatment in attention deficit hyperactivity disorder: a preliminary case
series, J.Child Adolesc.Psychopharmacol., vol. 12, no. 4, pp. 331-336.
P-15-14
Compensatory activity of cerebellum in cognitive impairment? An emission tomography study
Dario Saferstein
Imat, Neuroimaging, Buenos Aires, Argentina
J. Butman, M. Guirao
Introduction: Until recently, the cerebellum was held to play its role in
motor control. The pourpose of this study is to characterize cerebrocerebellar participation in non vascular cognitive decline. We investigated
asymmetry differences of right and left cerebellum in non vascular cognitive decline patients with left or right frontal hypoactivity.
Method: Twenty brain perfusion studies using 99Tc-Etilen Cistein Dimer
and 21 Fluor Desoxi Glucose studies were performed in 41 non vascular
decline cognitive patients with left or right frontal compromise.
Results: Cerebellum reveals consistently a perfusion asymmetry when
frontal hypoactivity asymmetry is present, compared with a normal database, by statistical parametric mapping.
Conclusion: This results show a trend towards a compensatory role of
cerebellum.
References: 1- Claeys KG, Orban GA, Dupont P, Sunaert S, Van Hecke P,
De Schutter E.Involvement of multiple functionally distinct cerebellar
regions in visual discrimination: a human functional imaging study
Neuroimage. 2003Oct;20(2):840-54. Pages 840-854 2- Chen SH,
Desmond JE. Temporal dynamics of cerebro-cerebellar network recruitment during a cognitive task.Neuropsychologia. 2005;43 (9):1227-37.
3-Mathiak K, Hertrich I, Grodd W, Ackermann H. Discrimination of temporal information at the cerebellum: functional magnetic resonance
imaging of nonverbal auditory memory. Neuroimage. 2004 Jan;
21(1):154-62. 4-Woodward TS, Cairo TA, Ruff CC, Takane Y, Hunter MA,
Ngan ET. Functional connectivity reveals load dependent neural systems
underlying encoding and maintenance in verbal working memory.
Neuroscience. 2006 Apr 28;139(1):317-25. 5-Loose R, Kaufmann C,
Tucha O, Auer DP, Lange KW. Neural networks of response shifting: influence of task speed and stimulus material. Brain Res. 2006 May 23;1090
(1):146-55. 6-Karlsgodt KH, Shirinyan D, van Erp TG, Cohen MS, Cannon
TD. Hippocampal activations during encoding and retrieval in a verbal
working memory paradigm. Neuroimage. 2005 May 1;25(4):1224-31.
7- Hester R, Garavan H. Executive Dysfunction in Cocaine Addiction:
Evidence for Discordant Frontal, Cingulate, and Cerebellar Activity The
Journal of Neuroscience, December 8, 2004, 24(49):11017-11022
8-WISER A. K. ; ANDREASEN N. C. ; OLEARY D. S. ; WATKINS G. L.;
BOLES PONTO L. L.; HICHWA R. D. Dysfunctional cortico-cerebellar circuits cause cognitive dysmetria in schizophrenia 9-Patterson II JC.,
Cerebellar Perfusion Abnormalities Correlated With Change in Cognitive
and Affective State in a 78-Year-Old Man. Am J Geriatr Psychiatry 9:309314, August 2001 Ullsperger M, von Cramon DY (2001) Subprocesses of
performance monitoring: a dissociation of error processing and response
competition revealed by event-related fMRI and ERPs. NeuroImage 14:
1387-1401.
179
P-15-15
Panic disorder and social phobia: Nosological entities or
preponderant symptoms?
Raul Fernando Iserhard
Porto Alegre, Brazil
Introduction: Panic Disorder and Social Phobia do not constitute nosological entities per se. Neurophysiological techniques as the QEEG with
Neurometric analysis seem not support this proposition.
Method: Presentation of the results obtained by means of QEEG with
Neurometric analysis in three patients with diagnoses of Panic Disorder
and/or Social Phobia (DSM-IV and ICD-10 criteria). Demographic and
medications data will be presented in the Poster
Results: The QEEG with Neurometric analysis data obtained from three
patients with the above mentioned diagnoses show a concordant concentration on Major Affective Disorder subtype Unipolar ( Depression).
Images and discriminant analyses will be provided in the Poster
Conclusion: The clinical implications directly derived from this feature
point, on one side, to the use of antidepressants as first choice medication, and perhaps, on the other, to the necessity of psychopathological and further nosological - revision of the basis of these two diagnoses.
180
PSYCHOPHARMACOLOGY - Poster
P-09
Psychopharmacology/Antidepressants
P-09-01
Short-term citalopram augmentation in partial/non responder major depressives: A randomized placebo-controlled
study
Carlo Altamura
University of Milan, Dept. of Psychiatry, Italy
Bernardo DellOsso, Massimiliano Buoli, Monica Francesca Bosi,
Emanuela Mundo
Introduction: Approximately 30%-45% of patients with a Major
Depressive Episode (MDE) do not fully respond to standard recommended treatments1and further strategies of intervention, including pharmacological augmentation, have been proposed for these patients2. The
present study was aimed to evaluate the efficacy of short-term, low-dose
(10 mg/day) iv. Citalopram augmentation vs Placebo in a sample of
patients with MDE and partial or no response to Selective Serotonin
Reuptake Inhibitors (SSRIs).
Method: Thirty-eight patients with a DSM-IV-TR MDE and partial or no
response to SSRIs were selected and randomly assigned to Citalopram
(n=16) or to Placebo (n=22) iv. augmentation. The augmentation regimen
lasted 5 consecutive days during which the patients were maintained on
their current treatment with oral SSRIs. ANOVA with repeated measures
on Hamilton Depression Rating Scale (HAM-D) and Montgomery-Asberg
Depression Rating Scale (MADRS) total scores administered daily were
done.
Results: With regard to the HAM-D total scores, a significant time effect
(F=48.834, p<0.0001), treatment effect (F=5.967, p=0.02), and timextreatment effect (F=25.097, p<0.0001) were found in favour of citalopram. Similar results were obtained from the analyses on the MADRS
total scores: time effect (F=46.532, p<0.0001) and timextreatment effect
(F=21.290, p<0.0001).
Conclusion: Our findings seem to indicate that short-term, low-dose,
intravenous citalopram augmentation may be efficacious in depressed
patients with partial/no response to SSRIs. Further controlled studies are
warranted to confirm these preliminary data.
References: 1. Fava M., Davidson KG. Definition and epidemiology of
treatment-resistant depression. Psychiatric Clinics of North America,
1996; 19 (2): 179-200. 2. Nemeroff CB. Augmentation strategies in
patients with refractory depression. Depress. Anxiety, 1996; 4 (4): 169181.
P-09-02
Atypical antipsychotics association to serotonin reuptake
inhibitors in patients with generalized anxiety disorder
Carlo Altamura
University of Milan, Dept. of of Psychiatry, Italy
Bernardo DellOsso, Massimiliano Buoli, Nazario DUrso, Emanuela
Mundo
Introduction: Recommended treatments for GAD include Selective
Serotonin Reuptake Inhibitors (SSRIs) along with Venlafaxine, Buspirone
and Benzos. Nonetheless, a consistent percentage of patients do not fully
respond to these therapies and specific augmentation strategies including
atypical antipsychotics have been proposed for individuals with partial or
no response. Recent studies1-3 have shown positive results in patients
with refractory GAD treated with augmentative antipsychotics
(Risperidone and Olanzapine). The present study was performed to assess
the efficacy of SSRIs vs SSRIs plus atypical antipsychotics in a sample of
GAD patients.
Method: The sample consisted of 26 patients (8 males and 18 females)
with DSM-IV-TR GAD, who were divided in 2 groups: one treated with
SSRIs in monotherapy for 8 weeks (n=13) and the other with SSRIs plus
atypical antipsychotics at flexible doses for 8 weeks (n=13). At baseline
and endpoint, patients were evalued with the Hamilton Anxiety Rating
Scale (HARS), Hamilton Depression Rating Scale (HDRS) and the Clinical
Global Impression Scale (CGI) . ANOVA with repeated measures were

done on HARS, HDRS and CGI scores. In addition, t-tests for paired data
were applied on pre and post-treatment scores in the two treatment
groups.
Results: The two groups of patients did not show any difference at baseline with respect to demographic and clinical variables including the
severity of illness. All patients were maintained on the same dosage of
SSRIs for all the duration of the study. In the group treated with atypical
antipsychotics plus SSRIs, the mean dose of Olanzapine at study endpoint was 7.08+6.97 mg/day, and 67.86+74.60 mg/day for Quetiapine.
Both groups showed a statistically significant improvement in anxiety
symptoms over time on the HARS (time effect F=89.348, p<0.001), HRDS
(time effect F=64.071, p<0.001) and CGI (time effect F=50.361,
p<0.001) scores. Differences between treatment groups were found in
favour of the combined treatment only in CGI scores (timextreatment
effect F=4.918, p<0.04; t-test for paired data t=5.579, p<0.001). All
patients reported mild to moderate side-effects without showing significant differences between the two groups of treatment.
Conclusion: These preliminary data would indicate a better global
improvement for patients treated with the association of SSRIs plus atypical antipsychotics than for patients treated with SSRIs monotherapy.
References: 1. Brawman-Mintzer O, Knapp RG, Nietert PJ. Adjunctive
risperidone in generalized anxiety disorder: a double-blind, placebo-controlled study. J Clin Psychiatry. 2005;66(10):1321-5. 2. Simon NM, Hoge
EA, Fischmann D, Worthington JJ, Christian KM, Kinrys G, Pollack MH. An
open-label trial of risperidone augmentation for refractory anxiety disorders. J Clin Psychiatry. 2006;67(3):381-5. 3. Pollack MH, Simon NM, Zalta
AK, Worthington JJ, Hoge EA, Mick E, Kinrys G, Oppenheimer J.
Olanzapine augmentation of fluoxetine for refractory generalized anxiety
disorder: a placebo controlled study. Biol Psychiatry. 2006;59(3):211-5.
P-09-03
Clinical characteristics and drug response to mood
stabilizers in late onset bipolar disorders
Carlo Altamura
University of Milan, Dept. of of Psychiatry, Italy
Bernardo DellOsso, Silvia Zanoni, Nazario DUrso, Bassetti Roberta,
Emanuela Mundo
Introduction: The present study was aimed to investigate for differences
in the basic clinical characteristics and drug response to mood stabilizers
between patients with earlier (< 45 years) or later (>45 years) onset
Bipolar Disorder (BD)1
Method: 103 patients with DSM-IV-TR BD I or II diagnosis, were selected. All patients gave their informed consent to participate into the study.
Patients were subdivided in two groups according to the age at onset
(> 45 years or < 45 years). The main demographic and clinical variables
were collected by clinical interviews (SCID-I) or review of the clinical charts
by expert psychiatrists, and then compared between the two groups
(Students t-test and chi-square tests). Response to mood stabilizers was
assessed by computing the number of major mood episodes occurring
during the 24 months before and after the start of Mood Stabilizers
(t-tests for paired data).
Results: 13.8% of patients had an age at onset > 45 years. Patients with
later onset BD had a shorter duration of untreated illness (DUI) (t=4.652,
p<0.04), and a lower number of mixed episodes occurring before mood
stabilizer treatment (t=3.498, p<0.001) than patients with earlier onset.
Patients were treated with lithium, Valproate, or Atypical Antipsychotics
as Mood Stabilizers and followed up for 24 months. In earlier onset BD
mood stabilizers were effective in reducing manic (t=3.749, p<0.001) and
depressive (t=3.323, p<0.001) recurrences, while in later onset BD mood
stabilizers were effective only in reducing manic recurrences (t=2.876,
p=0.01) but not depressive ones (t=0.001, p>0.9).
Conclusion: Patients with later onset BD may have significant clinical differences from patients with earlier onset BD. In addition, the lack of efficacy of Mood Stabilizers in preventing depressive recurrences in later
onset BD suggests that depressive episodes in this sub-group of BD
patients may need a specific clinical and pharmacological management2.
References: 1. Angst J, Gamma A, Sellaro R et al. Recurrence of bipolar
disorders and major depression. A life-long perspective. Eur Arch
Psychiatry Clin Neurosci, 2003; 253(5):236-40. 2. Altamura AC, Bassetti
181
R, Santini A, Frisoni GB, Mundo E. Emotional withdrawal, CT abnormalities and drug response in late life depression. Progr
Neuropsychopharmacol Biol Psychiatry, 2004, 28(2): 349-354.
P-09-04
Open study with escitalopram in depressed outpatients
with seasonal affective disorder
Dietmar Winkler
Medical University of Vienna, Dept. of General Psychiatry, Vienna,
Austria
Introduction: The dual serotonin reuptake inhibitor escitalopram
(Cipralex, Lexapro) has been approved for the treatment of major
depressive disorder, generalized anxiety disorder, panic disorder and social
anxiety disorder [1]. This study evaluated the clinical usefulness and safety
of escitalopram in the treatment of seasonal affective disorder (SAD).
Method: 20 SAD patients (14 females and 6 males) were included in an
8-week drug surveillance. Patients received treatment open-label escitalopram as a daily dosage of 10 to 20 mg. Study visits after baseline were
scheduled at week 1, week 2, week 4, week 6 and week 8. At each of
these visits patients were rated with the Structured Interview Guide for
the Hamilton Depression Rating Scale (SAD version; SIGH-SAD), the
Clinical Global Impression of Severity (CGI-S), the Clinical Global
Impression of Improvement (CGI-I), the CGI efficacy index and the Social
Adaptation Self-Evaluation Scale (SASS) [2]. Side effects were monitored
with the Udvalg for Kliniske Undersgelser (UKU) Side Effect Rating Scale.
Results: Escitalopram significantly reduced the SIGH-SAD score and CGI
severity score from week 2 on (p < 0.001). SASS score significantly
improved from week 4 on wards (p < 0.05). The response rate (SIGH-SAD
< 50% of baseline value) after 8 weeks of treatment was 95%, the rate
of remission (SIGH-SAD = 7) was 85%. Side effects were mild to moderate and did not lead to cessation of therapy.
Conclusion: The results of this open study show that escitalopram is an
effective and relatively well-tolerated psychopharmacological treatment
option for SAD. Further double-blind, randomized, placebo-controlled trials investigating escitalopram in SAD would be useful to confirm these
findings.
References: 1. Winkler D, Kasper S. Escitalopram. Arzneimitteltherapie
2004; 22: 97-102 2. Bosc M, Dubini A, Polin V. Development and validation of a social functioning scale, the Social Adaptation Self-evaluation
Scale. Eur Neuropsychopharmacol 1997; 7(Suppl 1): 57-70; discussion
71-73
P-09-05
Agomelatine in the treatment of patients with fall-winter
depression: Results of an open study
Dietmar Winkler
Medical University of Vienna, Dept. of General Psychiatry, Vienna,
Austria
Introduction: Agomelatine (S-20098, Valdoxan) is a novel antidepressant, which acts as a melatonin (MT1 and MT2) receptor agonist and as
a serotonin (5-HT2C) receptor antagonist [1]. Prior studies have suggested
that agomelatine is apt to restore disrupted circadian rhythms [2], which
have been implicated in the pathophysiology of seasonal affective disorder
(SAD, fall-winter depression). This study was aimed to examine the efficacy
and tolerability of agomelatine in the treatment of SAD.
Method: 37 subjects with a moderate or severe episode of recurrent
major depressive disorder, who fulfilled the criteria for the DSM-IV-TR seasonal pattern specifier, were treated with open-label agomelatine (fixed
dose: 25 mg daily in the evening) over 14 weeks. Efficacy assessments
included the Structured Interview Guide for the Hamilton Depression
Rating Scale (SAD version; SIGH-SAD), the Clinical Global Impression of
Severity (CGI-S) and Improvement (CGI-I) and the Circscreen [3].
Results: SIGH-SAD, CGI-S and CGI-I scores decreased significantly from
week 2 on (p < 0.001). Moreover, scores on the Circscreen (sum of items
1-5) improved significantly during the study (p < 0.001). Treatment with
agomelatine over 14 weeks resulted in a response rate of 75.7% (SIGHSAD < 50% of baseline value) and a remission rate (SIGH-SAD < 8) of
70.3%. Agomelatine was overally very well tolerated: only one adverse
event (fatigue during days 1 to 5) was related to the study drug.
182
Conclusion: Our results demonstrate that agomelatine is an effective and

safe treatment for SAD. Further randomized, placebo-controlled trials are
necessary to ascertain the results of this open study.
References: 1. Den Boer JA, Bosker FJ, Meesters Y. Clinical efficacy of
agomelatine in depression: the evidence. Int Clin Psychopharmacol 2006;
21 (Suppl 1): S21-24 2. Weibel L, Turek FW, Mocaer E, Van Reeth O. A
melatonin agonist facilitates circadian resynchronization in old hamsters
after abrupt shifts in the light-dark cycle. Brain Res 2000; 880: 207-211
3. Laredo J, Quera Salva MA, Falissard B, de Bodinat C. Screening of sleep
and circadian rhythms in major depression. J Sleep Res 2002; 11 (Suppl.
1): 132-133
P-09-06
Early response to venlafaxine antidepressant and remission are correlated with lower ACTH levels previous to the
pharmacological treatment
Jenny Fiedler
University of Chile, Biochemistry and Molecular Bi, Santiago, Chile
Paulina Rojas, Veronica Araya, Rosemarie Fritsch, Romina Rojas, Luisa
Herrera, Graciela Rojas, Hernan Silva
Introduction: Evidences suggest an alteration in the regulation of the
hypothalamic-pituitary-adrenal (HPA) axis associated with an increase in
cortisol secretion in depressive disorder. The goal of this study was to
investigate whether treatment response to venlafaxine antidepressant is
predicted by HPA axis parameters. As arginine-vasopressin (AVP) plays an
important role in the activation of HPA axis during stress, the present
study investigated the ACTH and cortisol secretion induced by AVP analogue desmopressine (ddAVP) in depressive patient and control subjects.
Also endocrinological parameters were correlated with venlafaxine antidepressant response.
Method: 18 depressive patients (with no other psychiatric pathologies)
completed 6 weeks of venlafaxine antidepressant treatment. The 17-item
Hamilton Depression Scale (HAM-D) was used to follow-up the response
to venlafaxine. Early response to venlafaxine was defined as a 25%
decrease in HAM-D during the first week of treatment. Response was
defined as a 50% decrease in HAM-D at week 6 and remission was considered with a HAM-D score = 7. At baseline, 24h urinary cortisol excretion, and cortisol and ACTH concentrations in ddAVP test were measured.
Non-parametric analysis was used to evaluate differences between
groups. In order to assess change over time of the variables between
groups of patients during treatment, repeated measurement analysis of
variance (ANOVA) was used.
Results: After one week of treatment, a 60% of patients behave as early
responder in contrast to late responder group (40%) that started to
reduce their HAM-D after 3 weeks. Both groups respond to treatment
after 6 weeks of treatment. Prior to the pharmacological treatment, late
responder group showed higher basal ACTH than both early responder
and control subjects. The ddAVP promoted ACTH secretion only in late
responder group. Remitters showed lower basal ACTH and cortisol secretion than non-remitters.
Conclusion: The results suggest that ACTH levels could be related with
the rate and treatment outcome. FONDECYT1040937
P-09-07
Relationship between antidepressants and the IGF-1 system in the brain: Possible role in cognition
Nurit Grunbaum-Novak
Felsenst. Inst. Tel Aviv Univ., Lab of Psychobiology, Petach Tiqva, Israel
Michal Taler, Irit Gil-Ad, Hagit Cohen, Avraham Weizman, Ronit Weizman
Introduction: Antidepressants were found to facilitate neuroplasticity
and cognition by stimulating trophic factors. Insulin-like-growth-factor-1
(IGF-1) is a potent neurotrophic factor in the brain. Previous studies have
demonstrated that IGF-1 accelerates brain growth and neuroplasticity.
IGF-1 is regulated by different neurotransmitters such as norepinephrine
(NE) and serotonin (5-HT). We aimed to evaluate the effect of selected
antidepressants, which act differently on 5-HT and on NE neurotransmitters,
on the IGF-1 system in different regions of the rat brain and to assess the
effect of IGF-1 on cognition.
Method: Frontal cortex and hippocampus were dissected from male

Wistar rats treated with reboxetine and fluoxetine given orally (15mg/kg
daily for 3 or 21 days). IGF-1 receptor (IGF-1R) expression was determined
by Western blot analysis. IGF-1 mRNA levels were assessed by semiquantitive PCR reaction. To determine the role of IGF-1 in cognition, rats were
injected with IGF-1 (5mcg/rat icv) and subjected to the Morris Water
Maze (MWM) and to the object recognition task (OR).
Results: In the frontal cortex, both drugs decreased IGF-1 mRNA levels
after 3d, and increased IGF-1 mRNA and receptor levels after 21d. In the
hippocampus, reboxetine increased the receptor expression after 3d. Both
drugs decreased IGF-1 mRNA levels, and reboxetine decreased also the
receptor levels after 21d. In the MWM, acute IGF-1 decreased the latencies to locate the platform. In the OR, the IGF-1 group tended to spend
more time with the new object and showed significantly higher exploration activity in the arena compared to controls.
Conclusion: Our results suggest that IGF-1 possesses a short-term cognitive enhancing effect. Selected antidepressants affect IGF-1 system in the
cortex and the hippocampus differently. After chronic treatment, the system is up-regulated in the frontal cortex, and tends to be down-regulated in the hippocampus. It is possible that antidepressants affect neuroplasticity through the IGF-1 system, and the frontal cortex might be one
of the main regions involved.
References: 1.DSa C., Duman RS. 2002, Antidepressant and neuroplasticity, Bipolar Disord, 4:183-194 2.Brian A. Hoshawa, Jessica E. Malbergb,
Irwin Luckia,c,T (2005) Central administration of IGF-I and BDNF leads to
long-lasting antidepressant-like effects, Brain Research 1037:204-208
P-09-08
Antidepressive treatment of major depression in
Parkinsons disease with venlafaxine
Anna Hoedl
Helmut Schoeggl, Karin M. Reisinger, Raphael M. Bonelli
Introduction: Major depression is a common sign in Parkinsons disease
(PD), but mostly underdiagnosed and undertreated. Although patients
suffer a lot there are little studies on antidepressive treatment in PD.
Method: To assess the efficacy of venlafaxine, a new serotonine and
noradrenaline reuptake-inhibitor, in major depression in PD, 22 inpatients at the Hospital BHB Eggenberg were examined. All patients suffered from idiopathic PD and major depression (mean age 70.11 a). Other
antidepressants were withdrawn at least 7 days before beginning of the
study, if required patients were prescribed a benzodiazepine for insomnia.
11 patients received the extended release preparation of venlafaxine,
11 received the non-retard preparation. Patients were assessed at week 0
and after 3 weeks of treatment with the Becks Depressions Inventar (BDI)
assessing major depression.
Results: Three patients in the non-retard group were withdrawn from the
study because of nausea and emesis. Patients receiving the extended
release preparation tolerated a higher dose of venlafaxine than the nonretard group (156.4 mg [SD 76] vs. 84.4 mg [SD 30]). The mean BDI at
week 0 for both groups was 31.0 (SD 7.92), at week three the mean BDI
was 12.42 points (SD 6.78). In the non-retard group one patient met the
criteria for remission (minimal symptomatic depression or no depression)
and in the extended release group 6 patients.
Conclusion: Venlafaxine is an effective antidepressant in major depression in PD, especially the extended release preparation shows good tolerability. To objectify results a larger, double-blind, placebo-controlled study
is needed.
P-09-09
Organic depressive disorder in Huntingtons disease:
Effective treatment with venlafaxine
Anna Hoedl
Daniela V. Otti, Markus M. Magnet, Raphael M. Bonelli
Introduction: A prominent sign in Huntingtons disease (HD), a hereditary, devastating disorder, is major depression, often caused by organic
malfunction of the brain. Organic major depression is frequently seen in
a prodromal stage of HD, when neurological and cognitive decline is not

present yet. As suicide rate in patients with HD and asymptomatic gene
carriers is much higher than in the general population effective treatment
of major depression in HD is crucial. In advanced stages of HD nearly
every patient suffers from depression, nevertheless only 16 studies on
depression in HD, assessing a total of 40 patients, have been published
until now (Bonelli and Wenning 2006).
Method: 25 in-patients of the Department of Psychiatry of the Graz
Medical University suffering from HD (9 women, 16 men) were treated
with a mean daily dose of 147 mg of venlafaxine (SD 50.7). All patients
were diagnosed as organic depressive after the criteria of ICD-10. A
Hamilton Rating Scale for Depression (HAM-D), a Hamilton Anxiety Scale
(HAM-A) and a Beck-Depressions-Inventar (BDI) were done before treatment and after 4 weeks (1 week) on antidepressive treatment. 3 HDpatients were asymptomatic (Shoulsons clinical stages 1), 9 in stage 3, 6
in stage 4, and 7 of all patients belonged to the most severely handicapped patients in stage 5 (Shoulson 1979).
Results: In one patient venlafaxine had to be withdrawn after five days
due to increasing restlessness. All other patients continued the treatment.
At week 4 1 week HAM-D, HAM-A and BDI showed significant better
results than at week 0 (see table). Clinical signs and symptoms of depression decreased remarkable. Venlafaxine was as effective in those 52% of
HD-patients in stage 4 and 5 who were already severely handicapped as
in the group of asymptomatic patients. m (SD) week 0 m (SD) week 41
p HAM-D 18.04 (6.64) 8.96 (4.40) 0.000* HAM-A 18.60 (9.95) 7.04
(5.15) 0.000* BDI 15.12 (5.50) 7.56 (3.28) 0.000* 0.000*= highly significant
Conclusion: As organic depression in HD is not easy to treat and patients
take mostly numerous drugs, Venlafaxine is an effective treatment in HD
and is well tolerated in those patients. Still suicide and depression are a
common cause of death in HD, therefore right treatment for these
patients and more studies on antidepressive treatment in HD are urgently
needed.
P-09-10
Influence of the antidepressant therapy on apoptosis of
lymphocytes in patients with depressive disorders
Nataliya Rakitina
Svetlana Ivanova, German Simutkin
Introduction: In last years interdisciplinary investigations of psychoneuroimmunomodulation in clinic and therapy of stress-related mental diseases are topical (Ader R., 1995). Apoptosis can be enhanced by a variety
of external stimuli, such as stress, viral infections, medications and pathological conditions. Psychotropic (antidepressant) medications can be
effect on various immune functions, including normal physiological programmed cell death of lymphocytes.
Method: We measured apoptosis in the MNLs (mononuclears lymphocytes of peripheral blood) of 18 patients with depression and in 20 ageand sex-matched controls. The investigation was carried out in dynamics:
before the beginning the pharmacotherapy against the background of
depressive symptomatology and after the course of medication with
selective serotonin re-uptake inhibitors (fluoxetine). We counted number
of leukocytes, percent CD95+lymphocytes and morphological changes
characteristic of apoptosis in lymphocytes.
Results: We observed significantly increased apoptosis in the MNLs of
depressive patients: the percentage of lymphocytes with expression FASreceptors was 19,471,02% ( 12,000,77% in control, p<0,05). Also,
we demonstrated a significant increase of cells with morphological
changes characteristic of apoptosis (nuclear condensation, vacuolation,
and blebbing) in the depressive patients (2,030,72% and 0,970,35%
in control, p<0,05). The normalisation of CD95+lymphocytes was
observed after the conducted treatment with selective serotonin reuptake inhibitors. Also, we demonstrated a significant decrease lymphocytes with fragmented nucleus in schizophrenic patients (0,230,08 %
and 0,970,35% in control, p<0,05).
Conclusion: Antidepressant therapy have potent immunomodulatory
properties, resulting in decreased levels of expressing receptors to Fasdependent death and apoptosis realization of immunocompetent cells.
Our results can explain findings obtained by others that showed reduced
183
NK activity and lower mitogen stimulation in depressed patients. Some of

these observations can be attributed to the increased apoptosis in these
cells. It is not yet clear whether this tendency could be attributed to a certain subpopulation of the MNLs or to the MNLs in general.
References: 1. Ader R., Cohen N., Felten D. (1995) Psychoneuroimmunology: interactions between the nervous system and the immune system //
Lancet. - Vol. 345 (8942). - P. 99-103.
P-09-11
Venlafaxine eficacy and tolerability in treatment of
patients with posttraumatic stress disorder
Alma Bravo Mehmedbasic
Centre for Torture Victims, Sarajevo, Bosnia and Herzegovina
Abdulah Kucukalic, Dubravka Salcic, Sabina Popovic
Introduction: Venlafaxine is an antidepressant with dual reuptake mechanism of action; inhibiting both the reuptake of serotonin and noradrenaline. It exhibits significant antidepressant action and it is a structurally
novel antidepressant. Venlafaxine is a powerful inhibitor of serotonin and
noradrenaline reuptake and a weak dopamine reuptake inhibitor. The
advantage of dual mechanism of action is in increased efficiency of serotonin and noradrenaline reuptake inhibition; this leading to faster and
stronger clinical response in the majority of subjects. Venlafaxine is a first
line treatment option for depression and depression with anxiety symptoms. It is safe and well tolerated in long-term treatment. Its pharmacokinetic and pharmacodynamic properties make venlafaxine an attractive
choice for the treatment of PTSD patients. The efficacy is maintained during long-term treatment. Compared with the SSRIs venlafaxine exhibits
faster clinical response and a higher percentage of clinical remissions. Its
side-effects are rare and time limited. Treatment with higher dozes of venlafaxine can be beneficial in reducing physical (including pain) and anxiety symptoms in PTSD subjects.
Method: The sample consisted of 30 patients with symptoms of
Posttraumatic stress disorder. All subjects received treatment with venlafaxine in therapeutic dose in the period of six months. All subjects were
assessed prior to therapy and in 3 month-follow-up and 6 months followup using of following instruments: Mississippi Questionnaire for PTSD,
The Clinical Global Impressions scale (CGI), and the Hamilton Depression
rating scale (HAM-D-21).
Results: The difference between three assessments with Mississippi
Questionnaire for PTSD was statistically significant. PTSD rate in our sample was reduced from 100% prior to treatment to 53% subsequent to
treatment with venlafaxine. The difference between three assessments
with The Clinical Global Impressions scale was statistically significant. The
results indicate statistically significant reduction of depression on the
Hamilton Depression rating scale (HAM-D-21), following six months
treatment with Venlafaxine. Venlafaxine was administered in daily doze of
112,5 mg in 80% of the subjects, and in the daily doze of 150 mg in the
remaining 20% of subjects. Unwanted effects were registered in three of
the subjects (increased blood pressure) and they were of mild intensity.
Conclusion: Venlafaxine proved to be very efficient, well tolerated and
safe in treatment of patients with Posttraumatic stress disorder.
References: Richard L. Rudolph, MD, Richard Entsuah, PhD, A MetaAnalysis of the Effects of Venlafaxine on Anxiety Associated With
Depression. Journal of Clinical Psychopharmacology;1998;18:212-221
P-09-12
Tianeptine and its neural plasticy effect in patients with
both severe depression and severe somatic i.e. organic
disorders and with cognitive and mnemonic disturbances
Eduard Pavlovic
University Hospital Center, Psychiatric Clinic, Rijeka, Croatia
Suzana Jonovska, Nikola Jonovski
Introduction: Depression can be accompanied by other mental and
physical disorders. The tretment of depression in comorbid patients
requires therapeutic adaption to their overall helth condition. The aim of
this study was to establish the neural plasticy effect of tianeptine in
patients with both severe depression and severe somatic i.e. organic disorders and with cognitive and mnemonic disturbances.
184
Method: This pilot study included 51 participants (17 male and 34

female), 40-61 years of age, suffered from severe depresion (ICD-10:F09)
and one or several severe organic contolled deseases (hepatic, cardiovascular, neurological, metabolic diseases, cancer or allergy) who were controlled during July 2006 at Psychiatric Clinic in Rijeka. Their depression
have been treated with tianeptine (Coaxil) in effective dose of 25 or
37,5 mg\\day within last 6 months. The evalutions included the following
instruments: 1. sociodemographic questionnaire, 2. The Montgomery and
Asberg Depression Rating Scale (MADRS), 3. physical i.e. organic disorder
questionnaire, 4. cognitive and mnemonic questionnaire and 5. compliance questionnaire. In statistic analysis of data were used Student t test
and Fisher exact test.
Results: Most female patients were treated with tianeptine in 25 mg/day
and most male patients were treated with tianeptine in 37.5 mg/day. Both
gender groups have had respondent treatment against physical i.e.
organic disturbances. The most of them are cardivascular patients but
some more male patients have had severe surgical operations. All participants had very severe cognitive and mnemonic disturbances before treatment with tianeptine. After treatment male patients showed better
improvement than female patients. The compliance were good in two
gender groups but female patients collaborated better than male ones.
Conclusion: This study shows that tianeptine (Coaxil) is the medicament
of choise for patients with both severe depression and severe physical i.e.
organic deseases and with cognitive and mnemonic disturbances.
References: Folnegovic-Smalc V., ed. Depressive disorders. Medicus
2004;23(2); Macher PJ,ed. Nauroplasticy. Dialogues in clinical neuroscience 2004;6(2); Novotny V, Faltus F. Tianeptine and fluxotine in major
depression: a 6-week randomised double-blind study. Hum Psychopharmacol Clin Exp 2002:17:299-303.
P-09-13
Duloxetine as an add-on treatment in resistant depression
Patricia Willis
Institute of biological, psychiatry, Buenos Aires, Argentina
Paula Oyhamburu, Andrea Marquez Lopez Mato
Introduction: According to the concept that depression is a systemis disease, duloxetine is considered an excellent antidepressant with a balanced and mixed profile, useful in many types of depression, not only in
that associated with pain or somatic symptoms.
Method: A 6 months open experience with duloxetine after total or partial failure with other treatments, in a population of 28 depressive
patients (20 women, 8 men between 26 and 76 years old), treated with
30 mgs- 120 mgs/day, during 4-6 weeks is presented. population included:unipolar, bipolar, anxiuos, somatic and non anxious patients.
Exclussion criteria were: associated neurologic pathology, involution signs,
pregnancy and lactation period. Clinical evaluation, Hamilton (Ham-D)
and Beck scales were assessed. Results were evaluated as: 1) excellent
response: non symptomatic; 2) very good response: more than 50%
improvement in Ham-D and beck scales: 3) partial response: less than
50% improvement; 4) no response; 5) dsicontinuation.
Results: 24 patients finished the study. 4 patients discontinued treatment
because of intolerable side effects. None of them discontinued treatment
because lack of efficiency. There was a 70% of response to treatment
with no significant differences between gender. Those with depression
associated with pain an d somatic symptoms revealed an excellent
response (21,4 %). Very good response (39,3%) was observed in other
types of depression. Partial response was observed in 5 patients (17,9%),
and only 2 had no response (7,1%). Adverse effects were observed only
in the beginning of treatment and did not last after two-three weeks
treatment. Most frequent were nausea (39,3%), dry mouth (25%), and
sleep changes (25%). Many can be avoided by changing the hour of
administration. Recurrency was not evaluated due to the short period of
time.
Conclusion: Duloxetine is useful in many types of depression (anxious,
inhibited, unipolar, comorbid diseases, and mixed depressions). Yhe effectiveness is observed between 60-120 mgs/day.
References: reference information will be further explained and were
based on the patients clinical evaluation in the Institute of Biological
Psychiatry.
P-16
Psychopharmacology/Antipsychotics
P-16-01
Physicochemical disparities between commercially available olanzapines
Daniel Flores
Eli Lilly Interamerica, Buenos Aires, Argentina
Livio Centanni, Jorge Rovner
Introduction: Olanzapine (2-methyl-4-(4-methyl-1-piperazinyl)-10Hthieno[2,3-b][1,5] benzodiazepine) is a proved antipsychotic agent indicated for the treatment of Schizophrenia and Bipolar I Disorder of the
thienobenzodiazepine class developed by Eli Lilly & Co and commercially
offered for over 10 years worldwide. Recent availability of different kinds
of olanzapines claiming similarity with the original product has been seen
in some countries. We have compared one of such copies regarding its
solubility at different pH and at different points in time within its
approved shelf life.
Method: An in vitro dissolution test was carried out using the USP 29
Apparatus II (paddle) method. Hanson Research equipment has been
used. Dissolution tests were performed in 900 ml of HCl 0.1 N for pH 1
and phosphate buffer of pH 4.5 at 37.0+/-0.5 C at 50 rpm for
30 min. Every point represents 3 to 6 measurements. Percentage of olanzapine dissolved at 15 and 30 minutes was reported.
Results: Dissolution tests performed after 1 year of manufactured at pH
1 have shown statistically significant differences between the original
product (Zyp) and the claimed similar product (Oli). At 15 minutes 93.3%
of Zyp and 76.8% of Oli dissolved (p<0.001). At 30 minutes 96.6% of
Zyp and 89.9% of Oli dissolved (p<0.05) After 18 months of manufactured at pH 1 after 15 minutes 68.8% of Zyp and 54.7% of Oli dissolved
(p=0.063) and after 30 minutes 104.5% of Zyp and 76.1% of Oli dissolved (p<0.001). When analyzed at pH 4.5 at 15 minutes 66.4% of Zyp
and 51.9 of Oli dissolved (p<0.01) and at 30 minutes 102.3% of Zyp and
72.1% of Oli dissolved (p<0.001). Values below 80% after
30 minutes are considered unacceptable for olanzapine.
Conclusion: In products soluble in water, dissolution rates correlates positively with bioavailability of such medications and significant disparities
could account for variations in the clinical effectiveness of the product.
Polymorphism of olanzapine is altered by humidity and in consequence its
solubility. We speculate that found differences in dissolution rates could
be due by differences in the crystallization form of the molecule and
diversity in the primary packaging (Aluminum-Aluminum for Zyp and
Aluminum-PVC for Oli).
P-16-02
Does weight gain affect treatment response in patients
with schizophrenia on olanzapine and haloperidol treatment?
Murad Atmaca
Firat University School of, Medicine, Dept. Psychiatry, Elazig, Turkey
B. Ustundag
Introduction: The relationship between body weight gain and clinical
efficacy of antipsychotics has not been enough analysed (1, 2). Therefore,
we aimed to investigate the relationship betwwen weight gain and antipsychotic efficacy.
Methods: The study comprised 24 patients (range 18-47 years). The
patients were divided into two groups randomizely: olanzapine (n=12)
and haloperidol (n=12) monotherapy. All participants were free of all
medications at least in the previous two weeks. All patients received a
routine hospital diet. The patients were evaluated at the baseline and
eighth week with respect to the Positive and Negative Syndrome Scale
(PANSS), weight, and serum leptinlevels. The leptin levels were measured
using enzyme-linked immunoassay (ELISA) method. All patients completed the 8-week study period as inpatients.
Results: The mean age was 28.35.3 years in the olanzapine group and
30.36.1 years in haloperidol treatment group (p=0.28). At the week 8,
the mean changes in weight for olanzapine and haloperidol groups were
4.83.1 and 1.50.8 kg, respectively (p=0.0023). There was statistically
significant difference regarding decrease in the mean PANSS scores in
olanzapine group compared to haloperidol group (from 95.26.1 to
72.65.2 in olanzapine group and 91.13.9 to 79.74.4; p=0.03). The
mean changes in leptin levels for the olanzapine and haloperidol groups
were 4.12.3, and 1.50.7 mg/dL, respectively (p=0.02). The change in
total PANSS scores correlated with change in leptin levels in olanzapine
group (r=0.58, p<0.05) but not in the haloperidol group (r=0.22,
p>0.05), and also with the change in weight in only olanzapine
group(r=0.75, p<0.01).
Conclusion: Our present study suggests that there may be a link between weight gain and leptin increase, and clinical efficacy of olanzapine.
On the other hand, it has been suggested that leptin could exert central
nervous system effects involved in the beneficial effect of antipsychotics
(3).
References: 1. Jalenques I, Tauveron I, Albuisson E, et al. Weight gain as
a predictor of long term clozapine efficiency. Clin Drug Invest
1996;12:16-25.2. Baptista T. Body weight gain induced by antipsychotic
drugs : mechanisms and management. Acta Psychiatr Scand 1999;100:316.3. Kraus T, Haack M, Schuld A, et al. Body weight and leptin plasma
levels during treatment with antipsychotic drugs. Am J Psychiatry
1999;156:312-314
P-16-03
Olanzapine induces early hyperplasia of subcutaneous
adipocytes in the absence of changes of cytokines in
female Wistar rats
Peter Yu
Neuropsychiatry Research Unit, Psychiatry, Saskatoon, Canada
Wei Tan, Hui Tan
Introduction: Olanzapine, an atypical antipsychotic, does not induce
extra-pyramidal side effects, but often causes weight gain in some
patients. Increase in body weight may lead to more serious health complications, i.e. diabetes and heart diseases. Therefore, it becomes a major
concern in compliance of health. The mechanism how atypical antipsychotics affect weight gain remains unclear.
Method: The present investigation employs female Wistar rats studying
the mechanism of Olanzapine-induced weight gain. Blood levels of glucose, triglyceride, 16 different cytokines, as well as the protein profiles,
morphological and histochemical alteration of the adipose in the
Olanzapine-treated animals were assessed.
Results: Olanzapine increased both feeding and body weight in these
rats, but data vary widely among individual rats and methods of handling
the animals. Data of the increase in adipose mass following chronic treatment was relatively consistent. Olanzapine also induces a dramatic and
highly reproducible morphological changes, i.e. pinkish color with an
appearance fish egg texture of the subcutaneous adipocytes.
Histological examination reveals an increase in hyperplasia of adipocytes.
It was detected as early as third days after treatment and become severe
in a time and dose dependent manner. The protein profiles in the adipose
are significant altered following chronic treatment of the drug. Using a
cytokine antibody arrays Olanzapine fails to show any affect of
16 cytokines in blood and adipose tested.
Conclusion: The occurrence of hyperplasia in the adipose of the
Olanzapine-treated rats in the absence of significant increase in feeding
and alteration of cytokines suggest that Olanzapine may directly affect
the adipose neurotransmitter function, since innervation has been shown
to affect adipocytes proliferation. [Supported by Canadian Institute of
Health Research and Saskatchewan Health Research Foundation]
185
P-16-04
Effect of dopamine D1 agonist A77636 on active allothetic
place avoidance, a spatial cognition task, in an animal
model of schizophrenia
Karel Vales
Institute of Physiology, Dep. Neurophysiology of Memory, Prague 4,
Czech Republic
Ales Stuchlik, Vera Bubenikova-Valesova
Introduction: Administration of noncompetitive NMDA receptor antagonists is used as animal model of schizophrenia-like behaviour. Blockade
of NMDA receptors with MK-801 causes specific behavioural changes,
including deficit in cognitive function. Results of recent experimental
studies have shown that D1-like receptors in prefrontal cortex (PFC) play
a key role in cognitive functions, preferentially for working memory, executive functions and attention. Aim of the present study was investigate
role of dopamine D1 receptors in spatial cognition using systemic administration of D1-specific agonist A77636 (0,1 and 0,5 mg/kg).
Subsequently, animals were tested on cognitive deficit induced by MK801 (0,1 mg/kg, s.c.) in the Active Allothetic Place Avoidance (AAPA) task.
Method: Active Allothetic Place Avoidance (AAPA) task, recently introduced behavioural paradigm, requires animals to actively avoid a roomframe-defined sector on a continuously rotation arena. A unique feature
of this task is that the rats have to solve a conflict between two discordant subsets of spatial stimuli. Information from the room frame is
brought into conflict with information from the arena frame by rotation
of the arena. This requirement that the subject differentiate between relevant and irrelevant stimuli, is similar to the concept that schizophrenic
patients are often unable to differentiate between relevant and irrelevant
stimuli because their information processing is impaired. Data was statisticaly evaluated by two-way ANOVA with MK-801 treatment as one factor and A77636 treatment as the second factor. Comparisons between
treatment groups were conducted using the Student-Newman-Keuls
Method post-hoc test.
Results: The results demonstrate that application of MK-801 increases
locomotor activity and decrease spatial efficiency in AAPA. D1 agonist
A77636 alone at doses 0,1 and 0,5 mg/kg improved the task solution.
But application of higher dose (1 mg/kg) was without effect on spatial
efficiency. Similarly, A77636 delimits cognitive deficit induced by application of MK-801 without effect on locomotor activity.
Conclusion: Our results with active allothetic place avoidance indicate
that activation of D1 receptors improve performance of cognitive functions only in specific concentration range. We conclude that in AAPA task
application of D1 agonist A77636 could improved spatial cognition and
delimit cognitive deficit. These findings support the notion that brain
dopaminergic D1 neurotransmitter system modulates neural processes
underlying spatial cognition in schizophrenia-like behavior. This research
was supported by grant MEYS 1M0517, LC554, GACR 309/06/1231 and
MHCR NR 9178-7.
P-16-05
A study of comparision of risperidone and conventional
neuroleptics in patients admitted to a privet psychiatry
hospital
Arivind Vaithiyam
Ram Psychiatry Hospital, Psychiatry, Madurai, India
Introduction: To compare the safety and efficacy of risperidone with that
of conventional neuroleptics in patients admitted to a private psychiatry
hospital for the treatment of psychotic symptoms and behavior.
Method: Of the 42 patients included in this reterospective chart review
study, 15 were admitted to the hospital for the first time and were treated
with risperidone on admission. The remaining 27 patients had been
admitted previously and had been treated with conventional neuroleptics.
During the current admission, these patients were switched from conventional neuroleptics to risperidone
Results: According to a 5-point clinical global impression scale, the current study found that 9 out of 15 patients (60%) admitted for the first
time showed marked to moderate improvement with risperidone compared with only 6 of the 27 patients (22%) treated with conventional
neuroleptics. When patients receiving conventional neuroleptics were
186
switched to risperidone, 19 (70%) improved. Patients treated with risperidone also showed significant improvement in several psychotic symptoms, including hallucinations, delusions and bizarre behavior. Adverse
effects were more common in patients treated with conventional neuroleptics.
Conclusion: Based on this finding the study concludes that risperidone is
safe and effective for treating psychotic symptoms in patients admitted to
a private psychiatry hospital.
References: Chouinard G,et al. A Canadian Multicenter placebo-controlled study of fixed doses of risperidone and haloperidol in treatment of
chronic schizophrenic patients. journal of clincal Psychopharmacaology
1993:13;25-40
P-16-06
Weight development in patients treated with risperidone:
A five year naturalistic study
Martin Neovius
Karolinska University Hospital, Institution Dept. of Medicine, Stockholm,
Sweden
Jonas Eberhard, Eva Lindstrm, Sten Levander
Introduction: To examine annual weight-development in a sample of
158 psychotic patients treated with risperidone over 5 years.
Method: Naturalistic longitudinal study.
Results: In patients with complete weight data (n=87), approximately
97% of the observed 5y weight gain (4.711.6kg) had been accumulated
after 2y. The dispersion was large in 5y weight and BMI changes
(6.712.9 vs. 3.010.3kg; 2.44.7 vs. 1.03.2kg/m2 for females and
males, respectively) and the gender differences did not reach statistical
significance. Patients becoming drug-free maintained their weight and
the average BMI gain in the study population was twice and 24 times
higher for males and females, respectively, compared to estimates from
the general population (1995-2002). Excessive weight gain (>7%) was
experienced by 40.2% of the patients and was weakly associated with
weight at baseline (=-0.2%; p=0.02), while independent of gender,
symptoms, years of illness, prolactine and nicotine.
Conclusion: Antipsychotic drug treatment resulted in significant weight
gain, which levelled off over time.
P-16-07
Erotomania treated with risperidone
Elvira Koic
General Hospital, Dept. of Psychiatry, Virovitica, Croatia
Introduction: In the case presented the female patient showed a clinical
picture of a pure, primary form of erotomania, i.e., de Clerambaults syndrome.
Method: The condition has been developing for ten years prior to the
first treatment attempt, which was unsuccessful until the psychotherapy
was combined with antipsychotic risperidone at the maintenance dose of
4 mg a day. In addition to risperidone the antidepressant fluoxetine was
used at the dose of 20 mg a day. The patient was treated in both inpatient and outpatient settings.
Results: We used antipsychotic risperidone (4 mg a day), and antidepressant fluoxetine (20 mg a day). After six months of treatment the patients
mental condition improved significantly.
Conclusion: Patient from the case presented suffered from the syndrome
of erotomania. Is a delusional disorder in which patients have delusions
that another person, usually more prominent or of a higher status, is in
love with them. The course of illness may be chronic, recurrent and brief.
The interview with the patient has to be conducted diplomatically. In the
assessment of potentially dangerous patients it is recommended to investigate if there are previous records of antisocial conduct, stalking, abuse,
jealousy, violence, aggression, or the existence of multiple objects of pursuit. Separation from the love object may be the only satisfactory means
of intervention. The combination of psychotherapy and pharmacotherapy
is most effective.
References: 1.de Clerambault GG. Les Psychoses Passionelles (1921), in
Oeuvre Psychiatrique. Paris, Presses Universitaires de France, 1942.
2.Signer SF. Les psychoses passionnelles reconsidered: a review of de
Clerambaults cases and syndrome with respect to mood disorders. J

Psychiatry Neurosci 1991; 16(2):81-90. 3. Muzinic L, Goreta M, Jukic V,
Dordevic V, Koic E, Herceg M. Forensic importance of jealousy. Coll
Antropol 2003; 27(1): 293-300. 4.Barkic J. Filakovic P, Radanovic-Grguric
L, Koic O, Laufer D, Pozgain I, Koic E, Hotujac L. The influence of risperidone on cognitive functions in schizophrenia. Coll Antropol 2003; 27
Suppl 1: 111-8.
P-16-08
Positive correlation between clinical side effects and
hyperprolactinemia among patients on risperidone
Ya Mei Bai
VGH, Taipei, Taiwan, Department of Psychiatry, Germany
Jen-Yeu Chen, Tzu Ting Chen, Wen-Ho Chang
Introduction: Hyperprolactinemia is a frequent side effect of risperidone,
associated with both acute (galactorrhea, amenorrhea, decreased libido
etc.) and chronic (osteoporosis and cardiovascular disease) emergent
effects. The dopamine system theory suggested that dopaminergic antagonism of antipsychotics within the tuberoinfundibular and nigrostriatal
systems were associated with elevated prolactin level and extrapyramidal
side effects, but no reports investigated the correlation of these two side
effects. The present study explored the correlation between porlactin
level, serum concentration of risperidone metabolites, and clinical side
effects, to test the possibility of clinical side effects as an index of hyperprolactinemia.
Method: The study sample was 50 schizophrenic patients who maintained on risperidone for more than three months. Clinical assessment
included Positive and Negative Syndrome Scale, Abnormal Involuntary
Movement Scale, Simpson Angus Scale (SAS), Barnes Akathisia Scale, and
Udvalg for Kliniske Undersogelser (UKU) Side Effect Rating Scale. Serum
concentration of metabolites of risperidone and 9-OH risperidone and
prolactin were measured.
Results: The study sample consisted of 25 male and 25 female patients,
with average age of 46.411.9, and risperidoen dose of 4.3 1.7. The
serum concentration of prolactin, risperidone, 9-OH risperidone, and total
metabolites were 56.335.7, 5.73.6, 8.75.3, and 14.37.2 ng/ml,
respectively. Significantly positive correlation between serum concentration of prolactin and 9-OH risperidoen (r=0.42, p=0.003) and total
metabolites (r=0.33, p=0.022) were noted. The prolactin level were also
positively correlated with side effects profiles: SAS total score (r=0.291,
p=0.062) [gait (r=0.288, p=0.043), wrist rigidity (r=0.263,p=0.065),
tremor(r=0.263,p=0.065), and salivation(r=0.349,p=0.013)] and UKU
total score (r=0.378, p=0.007), [Lassitude (r=0.305,p=0.031), emotional
indifference (r=0.315,p=0.026), hypokinesia (r=0.385,p=0.006), blurred
vision (r=0.346,p=0.014), and increased salivation (r=0.264,p=0.064)],
but without significant association with risperidone dose.
Conclusion: Positive correlations between serum concentration of prolactin, risperidone metabolites and side effects profiles supported the
hypothesis that simultaneous dopaminergic antagonism on the tuberoinfundibular and nigrostriatal systems. The prolactin level was not associated
with risperidne dose suggested inter-individual variation of metabolism
activity. However, the positive correlation of prolactin level and clinical
side effects indicated that when patients experienced more clinical side
effects, the clinicians should consider that the patients might have higher
concentration of risperidone metabolites and monitor the possibility of
hyperprolactinemia.
P-16-09
Long-term efficacy of ziprasidone in treatment-resistant
schizophrenia: Results from the 1-year, open-label mozart
extension study
Method: Subjects who completed a randomized, double-blind, 18-week

trial (MOZART) comparing clozapine and ziprasidone in refractory or
treatment-intolerant patients with schizophrenia and who responded to
treatment with ziprasidone (= 20% reduction in Positive and Negative
Syndrome Scale (PANSS) total score) were enrolled in a 1-year, open-label,
flexible-dose study. Subjects continued to receive the same dose of
ziprasidone (80-160 mg/day) as they were receiving when they completed
the double-blind study. Dose changes were permitted based on clinical
impression of efficacy or adverse events. The change in PANSS total score
from baseline to study end point and the proportion of patients maintaining = 20% PANSS improvement at study end point were recorded. Safety
measures included adverse events, laboratory tests, body weight, vital
signs, and electrocardiograms.
Results: Of 45 patients who completed the initial study, 42 were enrolled
in the extension study and 40 were included in the intent-to-treat analysis.
The mean change from core study baseline in PANSS total score was
37.0 (95% CI, 41.8 to 2.2; P < 0.001) on entry to the extension study.
Following 1 year of oral ziprasidone, the mean change in PANSS total
score from core study baseline was 32.2 (95% CI, 39.1 to 25.3; P <
0.001), a change from extension study baseline of 5.1 16.7 (P = 0.061).
Of the 40 patients, 28 (70%) maintained = 20% reduction in PANSS total
score (vs core study baseline) at the extension study end point. The safety
evaluation showed no detrimental effects.
Conclusion: These findings show that the efficacy and safety of ziprasidone observed in refractory or treatment-intolerant patients with schizophrenia are maintained in a long follow-up period.
P-16-10
Ziprasidone in hospitalized patients with schizophrenia:
Evidence for rapid dose titration
Anil Jina
Pfizer Inc., New York, USA
Lewis Warrington, Doug Vanderburg, Ruoyong Yang
Introduction: Optimal dosing of psychotherapeutic agents has implications for both symptom control and patient compliance. Trials of ziprasidone in bipolar mania and schizophrenia suggest a target dose of 120160 mg/d and that rapid titration to this level provides maximum symptom improvement.
Method: In this report, data from 2 similarly designed fixed-dose, placebo-controlled studies of ziprasidone (rapidly titrated to a target dose of
40, 80, 120, or 160 mg/d) in patients with acute schizophrenia were
pooled. A total of 369 patients received ziprasidone and 171 patients
received placebo. Efficacy was assessed using Positive and Negative
Syndrome Scale (PANSS) at Weeks 1 and 6 (last observation carried forward end point) of treatment. Tolerability was assessed by discontinuations (all-cause and due to adverse events) at the relevant visits.
Results: There was a significant linear dose-response relationship
between ziprasidone dose and PANSS total score (F = 12.32, P = 0.001).
All ziprasidone doses produced statistically significant improvement in
PANSS total score; the largest effect size (0.52) was observed for the
160 mg/d group. At Week 6, least-squares mean PANSS total score
decreases from baseline were 9.98, 9.54, 11.71, and 14.87 in 40, 80,
120, and 160 mg/d groups, respectively. The corresponding placebo
decrease was 2.79. At Week 1, least-squares mean PANSS total score
decreases from baseline were 6.18, 5.70, 7.80, and 8.96 in 40, 80, 120,
and 160 mg/d groups, respectively. The corresponding placebo decrease
was 0.84. Tolerability of ziprasidone 160 mg/d was comparable with that
of lower doses.
Conclusion: Rapid titration of ziprasidone to 160 mg/d was associated
with greater efficacy compared with lower doses and was well tolerated
in these studies.
Emilio Sacchetti
Brescia University School of M, University Psychiatric Unit, Italy
Fabio Romeo, Anil Jina
Introduction: The purpose of the present study was to evaluate the efficacy and safety of ziprasidone over a 1-year, follow-up period, in a sample of treatment-resistant and/or intolerant patients with schizophrenia.
187
P-16-11
The impact of food on absorption of ziprasidone
Anil Jina
Pfizer Inc., New York, USA
Jeffrey Alderman, Jeffrey Miceli, Keith Wilner
Introduction: Oral ziprasidone shows increased bioavailability when
taken with food. Here we describe 2 pharmacokinetic studies to quantify
the impact of food on ziprasidone absorption.
Method: The first study, an open-label, 6-way crossover design, investigated ziprasidone absorption in 8 healthy males. Subjects received oral
ziprasidone (20, 40, and 80 mg) after an 8-hour fast or immediately following an FDA standard meal (60% fat). The second, an open-label, randomized, 3-way crossover study, explored the impact of dietary fat on
ziprasidone absorption in 14 healthy subjects. Subjects received ziprasidone (40 mg) under 3 conditions: fasting, with an FDA standard meal
(60% fat), and with a 30%-fat meal.
Results: In the first study, AUC was greater in fed than fasting states at
each dose (20 mg, +48%; 40 mg, +87%; 80 mg, +101%). Increases in
AUC and Cmax with dose were only linear in the fed state. In the second
study, decreasing the fat content had a modest impact on ziprasidone
absorption. AUC increased by 100% (60%-fat meal) and 80% (30%-fat
meal) relative to the fasting state. These increases can be attributed to
enhanced ziprasidone solubilization, leading to greater intestinal absorption. Less pharmacokinetic variability was observed in the fed state, suggesting more consistent absorption of ziprasidone when taken with food.
Conclusion: These results demonstrate that administration of ziprasidone
with food is crucial to ensure optimal absorption and necessary for linear
pharmacokinetics. Food will also provide greater consistency in daily systemic exposure to ziprasidone and, thus, better symptom control and tolerability.
P-16-12
Association between plasmatic levels of clozapine and his
metabolite: Risk factor study
Cesar Jara
Instituto Psiquiatrico, Psiquiatria, Santiago, Chile
Roberto Gallardo, Juan Soncini, Gustavo Murillo, Diana Penna, Alberto
Salas, Juan Sanchez, Miguel Morales, Maritza Alderete, Eugenio Olea
Introduction: It has been considered in the literature as a important risk
factor when rate is bigger than 0.70 between nor-demethylclozapine/clozapine. It is known that to establish this association can
avoid the intoxication of the patients underwent to a clozapine treatment. The subject of this work is to realized a prospective study in adults,
both sex schizophrenic patients
Method: The sample of 911 schizophrenic patients hospitalised were
analysed. A total of 4442 of plasmatic levels of clozapine and nordemethyl clozapine were studied by HPLC method during ten years
(1996-2006).
Results: The plasmatic levels of Clozapine and nor-demethyl-clozapine
showed a significant correlation with a R of 0.797, p < 0.01 (n = 4440).
Fig1. Global rate between plasmatic level of nor-demethyl-clozapine/
clozapine was 0.53.
Conclusion: Internationally is accepted as risk factor the rate of 0.7
between nor-demethyl-clozapine/clozapine. However, our chronic sample
of patients treated the global rate was 0.53. The variability that present
the relation of nor-demethyl-clozapine/clozapine was increase in great
plasmatic levels.
188
References: Oyewumi L. et al.. Relation of blood counts during

Clozapine Treatment to serum concentrations of Clozapine and nor clozapina. Can J. Psychiatry , 47 (3), 2002. Olesen O.V. et al.. Clozapine serum
levels and side effects during steady state treatment of schizophrenic
patients: a cross sectional study. Psychopharmacology 117 (3): 371-378,
1995.
P-16-13
Clozapine oral dose and plasmatic levels in refractory
schizophrenic patients
Cesar Jara
Roberto Gallardo, Alejandra Armijo, Nour Benito, Mariana Monarde,
Sandra Araya, Patricio Galvez, Ruben Nachar, Diana Penna
Introduction: Clozapine plasmatic levels are relevant to know the patient
adherence to treatment. The interaction with other drugs or concomitant
illnesses can modify these values. The aim of this research was to estimate
clozapine mean and maximun doses. There are scanty data in scientific
literature about these values estimated for chilean population.
Method: Clozapine doses were measured in 911 schizophrenic refractory
patients and their corresponding plasmatic levels were assessed from
4442 blood samples obtained and analysed during ten years (19962006). The group of patients considered only adults and the statistic
analysis was accomplished without considering variables like weight, age
or sex.
Results: The mean oral dose of clozapine was 412158 mg with a median value of 400 mg. The plasmatic mean level of clozapine was 632
389 ng/ml and the median value was 548 ng/ml. Of the entire group, only
8 cases were treated with the maximum dose of 900 mg and their respective 31 blood samples allowed to determine a mean of 1.083 ng/ml and
a median of 911 ng/ml.
Conclusion: It was determined that an exceptionally low number of
patients reached 900 mg of clozapine, the maximum dose internationally
recommended. It is also remarkable that plasmatic levels of clozapine
allowed to know with precision the nature of treatment of each patient
an even to detect patients that were not using it.
References: Greenwood-Smith C. et al. Serum clozapine levels:a review
of their clinical utility.Journal of Psychopharmacology Vol.17,(2).234238.2003 Ulrich et al Therapeutic drug monitoring of clozapine and
relapse a retrospective study of routine clinical data. Int J. Clinical
Pharmacol Ther 41(1):3-13.2003
P-16-14
Clozapine induced anticholinergic effects in geriatric
patients: Plasmatic levels importance. A case report
Cesar Jara
Roberto Gallardo, Diana Penna, Natalia Clavijo, Juan Sanchez, Maria I
Covarrubias, Margarita Faunes, Carlos Cid
Introduction: The efficacy and safety of clozapine is still in evaluation in
geriatric patients who are more sensitive than young patients. They present orthostatic hypotension, anticholinergic symptoms and central nervous system side effects. The aim of this study was to analyze a case of a
female patient that showed an anticholinergic syndrome, in which plasmatic levels were used as guides for diagnosis and treatment
Method: It is presented a 78 years old female patient treated for 10 years
with clozapine. She showed signs of postration and sensorium compromise (delirium), alteration of intestinal transit (ileum and constipation),
with no digestive organic pathology.
Results: Plasmatic levels of clozapine were suddenly doubled
(1330 ng/dl) as compared to previous levels. After drug withdrawal and
replacement with another atypical antipsychotic agent (risperidone), the
patient improved the sensorial and intestinal symptoms until complete
recuperation was achieved
Conclusion: Older schizophrenic patients under pharmacological treatment with clozapine require special controls and permanent plasma monitoring. Plasmatic levels association to physical morbidity can be used efficiently as an alternative.
References: Schneider L et al. Efficacy and adverse effects of atypical

antipsychotics for dementia: meta-analysis of randomised placebo-controlled trials. Am. J. Geriatr. Psychiatry 14 (3): 191-210, 2006 Szymanski
D. O et al. Anticholinergic delirium caused by retreatment with clozapine.
Am. J. Psychiatry 148:1486,1991. Levin et al. Death from Clozapineinduced constipation. Case report. Psychosomatics 43: 71-73, 2002.
P-17
Psychopharmacology/Antidepressants II
P-17-01
Recurrence prevention with 12 months of Venlafaxine XR
treatment in patients with recurrent depression
Jeff Musgnung
Pennsylvania, USA
Martin Keller, Bing Yan, David Dunner, James Ferguson, Edward
Friedman, Alan Gelenberg, Robert Hirschfeld, James Kocsis, Susan
Kornstein
Introduction: Introduction: We report results from the first 12 months of
a 2-year maintenance study evaluating long-term efficacy of venlafaxine
extended-release (XR) in preventing recurrence of MDD.
Method: Patients with recurrent unipolar MDD (N=1096) were randomized in a 3:1 ratio to receive 10-week acute phase treatment with venlafaxine XR (75 mg/d to 300 mg/d) or fluoxetine (20 mg/d to 60 mg/d),
followed by a 6-month continuation phase for responders. Subsequently,
at the start of 2 consecutive, double-blind 12-month maintenance phases,
venlafaxine XR responders were randomized to venlafaxine XR or placebo.
Time to recurrence was evaluated using Kaplan-Meier methods and compared between groups using log-rank tests.
Results: In this phase, 129 patients in each group were evaluated for efficacy. The probabilities of recurrence through 12 months were 23.1%
(95% CI: 15.3, 30.9) and 42.0% (95% CI: 31.8, 52.2) for venlafaxine XR
and placebo, respectively (P=0.005).
Conclusion: Twelve months of venlafaxine XR maintenance therapy was
effective in preventing recurrence in depressed patients who responded
to acute and continuation therapy with venlafaxine XR.
P-17-02
Two years of maintenance treatment in patients with
recurrent unipolar major depression: Efficacy of
Venlafaxine xr 75 mg/d to 225 mg/d
Jeff Musgnung
Pennsylvania, USA
James Kocsis, Susan Kornstein, Saeed Ahmed, Tahmina Ferdousi,
Michael Thase, Edward Friedman, Boadie Dunlop, Bing Yan, Ron
Pedersen
Introduction: The efficacy of venlafaxine extended-release (XR) at doses
between 75 mg/d and 300 mg/d has been demonstrated in patients with
recurrent major depressive disorder (MDD) over 2.5 years. As 300 mg is
above the maximum approved dose for venlafaxine XR in most countries,
a reanalysis was undertaken focusing on the patients taking
=225 mg/day.
Method: In the primary multicenter, double-blind trial, outpatients with
recurrent MDD (n=1096) were randomized to 10-week acute phase treatment with venlafaxine XR (75 mg/d to 300 mg/d) or fluoxetine (20 mg/d
to 60 mg/d), followed by a 6-month continuation phase. Subsequently, at
the start of 2 consecutive, double-blind, 12-month maintenance phases,
venlafaxine XR responders were randomized to venlafaxine XR or placebo.
Data from 24 months of maintenance treatment were analyzed for the
combined end point of maintenance of response (ie, no recurrence of
depression and no dose increase >225 mg/d), and each component individually. Time to each outcome was evaluated with Kaplan-Meier methods and compared using log-rank tests.
Results: The analysis population included 114 venlafaxine XR patients
who had received doses =225 mg/d prior to maintenance phase baseline
(venlafaxine XR: n=55; placebo: n=59). During the 24-month maintenance phase, 7 venlafaxine XR patients required a dose increase above 225
mg/d, 4 had a recurrence; 16 placebo patients required a dose increase,
7 had a recurrence. Probability estimates for maintaining response were
70% for venlafaxine XR and 38% for placebo (P=0.007), for no dose
increase above 225 mg/d were 76% and 58%, respectively (P=0.019),
and for no recurrence were 87% and 65%, respectively (P=.099).
Conclusion: These data confirm venlafaxine XR is effective maintaining
response at doses =225 mg/d for up to 2.5 years in patients with MDD.
P-17-03
Brain-derived neurotrophic factor gene polymorphisms and
mirtazapine response in Korean with major depression
Min-Soo Lee
Korea University, Psychiatry, Seoul, Republic of Korea
Myoung-Jin Choi, Mi-Young Ji, Sang-Woo Hahn
Introduction: This study was to determine the relationship between the
Val66Met polymorphism in the BNDF gene and the response to mirtazapine in a Korean population with major depressive disorder (MDD).
entered the study. Their clinical symptoms were evaluated with the HAMD-21 scales at baseline and after 1, 2, 4 and 8 weeks of treatment.
Results: Main effect of genotype or effect of genotypetime interactions
on the decrease of HAMD score over the 8 weeks follow-up was not
found. However, significant effect of genotype or allele carrier on the
decrease of psychic anxiety score over the 8 weeks was also found
(Genotype: F=5.593, p=0.004; Allele carrier: F=11.074, p=0.001). But
effect of genotype - time interactions on the decrease of HAMD score
over the 8 weeks follow-up was not found. T-test was used the evaluation the effect of the Val66Met polymorphism on the psychic anxiety
improvement at each of time period. There were significant differences in
the anxiety scores after 1th week and 2nd week of mirtazapine administration. The anxiety scores were lower for with the Met allele group than
for without the Met allele group after 1th week (p=0.007) and 2nd week
(p=0.028) of mirtazapine administration.
189
Conclusion: However Val66Met polymorphism is affecting the psychic

anxiety improvement, our results do not support the hypothesis that the
Val66Met polymorphism is involved in the therapeutic response to mirtazapine in Korean patients with major depressive disorder.
References: S.J. Tsai, C.Y. Cheng, Y.W. Yu, T.J. Chen, C.J. Hong,
Association study of a brain-derived neurotrophic-factor genetic polymorphism and major depressive disorders, symptomatology, and antidepressant response, Am. J. Med. Genet. 123B (2003) 19-22.
P-17-04
Two-year placebo-controlled maintenance study with
Venlafaxine XR in patients with recurrent major depression
Jeff Musgnung
Pennsylvania, USA
Martin Keller, Bing Yan, David Dunner, James Ferguson, Edward
Friedman, Alan Gelenberg, Robert Hirschfeld, James Kocsis, Susan
Kornstein
Introduction: To evaluate efficacy and safety of venlafaxine extendedrelease (XR) in preventing recurrence of depression.
Method: Patients with recurrent unipolar MDD (n=1096) were randomized in a 3:1 ratio to 10-week acute phase treatment with venlafaxine
XR (75 mg/d to 300 mg/d) or fluoxetine (20 mg/d to 60 mg/d), followed
by a 6-month continuation phase for responders. Subsequently, at the
start of 2 consecutive, double-blind, 12-month maintenance phases, venlafaxine XR responders were randomized to venlafaxine XR or placebo.
Time to recurrence was evaluated using Kaplan-Meier methods and compared between groups using log-rank tests.
Results: In this phase, the probabilities of recurrence through 12 months
in the venlafaxine XR (n=43) and placebo (n=40) groups were 8.0% (95%
CI: 0.0, 16.8) and 44.8% (95% CI: 27.6, 62.0), respectively (P<0.001).
Conclusion: An additional 12 months of venlafaxine XR maintenance
therapy was effective in preventing recurrence in depressed patients who
had responded to venlafaxine XR after acute, continuation, and
12 months of initial maintenance therapy.
P-17-05
G-protein Beta 3 Subunit C825T polymorphisms and mirtazapine response in Korean with major depression
Sang Woo Han
Soon Chun Hyang University, Psychiatry, Seoul, Republic of Korea
Min-Soo Lee, Rhee-Hun Kang
Introduction: G-protein 3 Subunit (GNB3) gene is a candidate gene for
influencing the clinical response to treatment with antidepressants. This
study was to determine the relationship between the C825T polymorphism in the G-protein 3 Subunit gene and the response to mirtazapine
in a Korean population with major depressive disorder (MDD)
entered the study. Their clinical symptoms were evaluated with the HAMD-21 scales at baseline and after 1, 2, 4 and 8 weeks of treatment. DNA
was extracted from the peripheral blood and all polymorphisms were
examined using a polymerase chain reaction (PCR) method.
Results: There was a significant main effect of time (p<0.0001) and, as
expected, a significant effect on the decrease in the HAMD score over the
8-week follow-up. But a main effect of or an interaction of genotype with
time on the decrease in the HAMD score over the 8-week follow-up was
not found. ANOVA test-based evaluation of the effect of the GNB3
T825C polymorphism on the decrease in the HAMD score at each time
period did not reveal significant differences.
Conclusion: However C825T polymorphism of the G-protein b3 subunit
gene(GNB3) is affecting the pathogenesis of major depressive disorder,
our results do not support the hypothesis that the C825T polymorphism
is involved in the therapeutic response to mirtazapine in Korean patients
with major depressive disorder.
190
P-17-06
Clinical efficacy of combined application of hypericum
extract and light therapy in depressive disorders
German Simutkin
Mental Health Institute, Affective States Department, Tomsk, Russia
S. Vasilyeva, L. Gorshkova
Introduction: Comparative assessment of efficacy of monotherapy with
Negrustin (preparation on the base of hypericum extract made by firm
Hexal AG, Germany; 1 capsule Negrustin corresponds to 1300 mcg
of Hypericini) and combination of Negrustin with light therapy in
depressive disorders.
Method: in the course of 4 weeks of an open controlled randomized
investigation of 20 inpatients (2 men and 18 women) aged 44,212,7
years, suffering from depressive disorders (depressive episode - 3 persons;
recurrent depressive disorder - 2 persons, dysthymia - 10 persons and
depressive reaction - 9 persons; severity of depression in 12 cases was
regarded as mild, and in 8 cases as moderate), were distributed into two
matched groups basic (Negrustin and light therapy) and control
(Negrustin). Dose of Negrustin constituted 2 capsules a day. Light
therapy was conducted with lamps of daylight (2500 luxes, morning and
evening sessions, 90 minutes each). In dynamic of treatment total score
according to SIGH-SAD (Structured Interview Guide for the Hamilton
Depression Rating Scale, Seasonal Affective Disorders Version; Williams J.
et al., 1991) and level of severity of disease according to CGI were identified.
Results: In basic group total score according to SIGH-SAD at baseline
constituted 23,33,1, at day 14 of the investigations 11,92,0, at day 28
of the investigation 3,41,3 scores. In control group respective indices:
20,21,5; 11,81,7; 6,31,4 scores. In basic group trend to more severe
reduction of degree of severity of depression was noticed to week 4 of
the therapy (p=0,1). Severity of disease according to scale CGI reliably
(p<0,01) reduced from 3,90,2 to 1,60,2 scores to the end of the treatment for basic group and statistically insignificantly (p>0,05) from
3,40,2 to 1,40,2 scores for control group. In the course of conducted
therapy in no case phototoxic reactions were observed.
Conclusion: Trend to higher clinical efficacy of combined application of
Negrustin and light therapy as compared with monotherapy with
Negrustin in relation to depressive disorders. Better clinical effect of
combination of light therapy and Negrustin in treatment of depressive
disorders may be associated with their mutual potentiation as well as with
possible decrease of the threshold for biological action of bright light
against the background of intake of hypericum.
P-17-07
Efficacy of duloxetine in the treatment of unspecific pain
associated with depression
Stefan Brecht
Boehringer Ingelheim GmbH, Dept Medical Affairs, Ingelheim, Germany
Christine Courtecuisse, Catherine Debieuvre, Jens Croenlein, Durisala
Desaiah, Joel Raskin, Koen Demyttenaere
Introduction: Painful physical symptoms (PPS) in major depressive disorder (MDD) can obscure the diagnosis and impair treatment outcome.
Antidepressants inhibiting serotonin and norepinephrine reuptake (SNRI)
can be effective in the treatment of both emotional and PPS in MDD. This
study evaluated efficacy and safety of duloxetine, an SNRI, in the treatment of patients with moderate pain associated with depression.
Method: In this double-blind, placebo-controlled, European, 8-week
study, outpatients _18 years of age, presenting with major depression
(Montgomery-Asberg Depression Rating Scale [MADRS] _20 and Clinical
Global Impression-Severity [CGI-S] _4) and moderate pain (brief pain
inventory [BPI] average pain score _3) not attributable to a diagnosed pain
syndrome were randomized to either placebo (N=165) or duloxetine
60 mg (N=162) once daily. Primary outcome measure was the BPI average pain score at endpoint. Secondary measures were MADRS total score,
CGI-S, PGI-I, SCL-90 R, response and remission in MDD, safety, and tolerability.
Results: Duloxetine compared with placebo significantly (P <.001) improved the mean change of both BPI average pain (-2.57 vs. -1.64) and
MADRS total scores (-16.69 vs. -11.31) with significant separation after
1 or 2 weeks. Remission in MDD (53% vs. 29%) and response rates in
pain (60% vs. 44%) and MDD (55% vs. 35%) were significantly higher
in duloxetine-treated patients as compared with placebo. Duloxetine
separated on most secondary outcome measures from placebo.
Treatment-emergent adverse events (_10%) observed in duloxetine- treated patients were nausea, hyperhydrosis, and dry mouth.
Conclusion: These results support duloxetines efficacy and tolerability in
the treatment of PPS and emotional symptoms in patients with moderate pain associated with depression.
with psychotic features and N=40 patients with nonpsychotic depression.

Medication dosage was started at 50 mg daily raised up to 100 mg daily
after one week period.If patients had not remitted we raised 50 mg every
two weeks.
Results: Response rate was significantly higher in nonpsychotic depressive patients 75% than in psychotic depressive patients 32%.
Nonpsychotic depressed patients responded earlier than patients with
psychotic features.
Conclusion: Response rate in patients with psychotic depression to
Sertraline therapy is lower than in nonpsychotic depressed patinets.The
psychotic features were a predictor of response independant on degree
of depression.
P-17-08
Switching to duloxetine from other antidepressants:
A regional multicenter trial comparing two switching
techniques
P-17-10
The optimal dose of sertraline in the treatment of depression
David Perahia
Eli Lilly & Company, Surrey, United Kongdom
Deborah Quail, Durisala Desaiah, Kurt Rasmussen
Introduction: To compare 2 methods of switching selective serotonin
reuptake inhibitor (SSRI) non- or partial responders to duloxetine.
Method: Adult outpatients with major depressive disorder (MDD), a
Hamilton Depression Rating Scale (HAMD17) total score of 15, and a
Clinical Global Impression of Severity (CGI-S) score of 3 despite at least
6 weeks of SSRI treatment, were randomized to either abrupt discontinuation of SSRI immediately followed by initiation of duloxetine (direct
switch; DS) or tapered discontinuation of SSRI over 2 weeks and simultaneous administration of duloxetine (start-taper switch; STS). The primary
outcome was non-inferiority of DS compared with STS as measured by
comparison of mean change in HAMD17 total score after 10 weeks of
duloxetine treatment. Other efficacy measures included response rates
(50% decrease in HAMD17 total score), remission rates (HAMD17 total
score 7 at endpoint), and visual analogue scales for pain. Safety and
tolerability were assessed via adverse events (AEs), vital signs, and labs.
Results: There was a significant improvement in depressive symptom severity in both switch groups as measured by mean change in HAMD17 total
score, but no difference between the groups (-10.23 DS vs -10.49 STS; P
= .698). Criteria for non-inferiority of the DS group were met. The switch
groups also were similar with respect to response (54.4% DS vs 59.6%
STS; P = .360), remission (35.7% DS vs 37.2% STS; P = .849), and other
secondary measures. There was a significant within-group improvement
for all efficacy measures (P <.01). Few patients experienced a serious
adverse event, and there was a low rate of discontinuation due to AEs
(6.6% DS vs 3.8% STS). Headache, dry mouth, and nausea were the most
frequently reported AEs. Subgroup analysis according to SSRI at study
entry did not suggest differential efficacy, safety or tolerability associated
with any particular SSRI following duloxetine switch.
Conclusion: Switch to duloxetine was associated with significant improvements in both emotional and painful physical symptoms of depression,
and was well tolerated and safe, regardless of which switch method was
used and which SSRI the patient was taking at study entry.
P-17-09
The efficacy of sertraline in the treatment of psychotic and
nonpsychotic depression
Valentina Calovska Samardziska
Clinic of Psychiatry, Biological Psychiatry, Skopje, Macedonia, Republic of
the former Yugoslav
Elizabet Miceva Velickoska, Nensi Manuseva, Branko Stefanovski,
Mirjana Polazarevska, Vilma Videnova
Introduction: Sertraline is a antidepresant used in the treatment of
depression.Our investigation is a commparative study of the efficacy of
Setraline in both psychotic and nonpsychotic depressed patients.
Method: In our study we analysed 80 patients treated with Sertraline
within a eight week period on the Clinic of Psychiatry. For diagnostic criteria we used MKB 10 and Hamilton Rating Scale that was repeated in a
two week period.The patients were divided in two droups. N=40 patients
Elizabet Miceva Velickoska

Clinic of Psychiatry, Biological Psychiatry, Skopje, Macedonia, Republic of
the former Yugoslav
Valentina Calovska Samardziska, Viktorija Vujovic, Antoni Novotni, Nensi
Manuseva, Mirjana Polazarevska
Introduction: Sertralin is a SSRi antidepressant commonly used in
Macedonia in the treatment of depressive patients.Our study was in order
to determine the optimal dose and suitable duration of Sertraline in the
treatment of depression.
Method: In our retrospective study we treated 120 depressed outpatients
at the Clinic of Psychiatry during a 3 month period, 2006.The comparation during the study was between the dose responce and the initial clinical action of Sertraline.
Results: Our results improved that high daily doses (100 mg) Sertraline
were more effective than lower doses (50-75 mg).The percentage of
improved patients was more than 75% in a five week period.
Conclusion: Sertraline is a effective antidepresant in the treatment of
depression in a recommended daily dose of 100 mg.If improvement has
not been seen within five weeks the daily doses should be increased in a
next 3-4 week period. After this period Sertraline should be altered.
P-17-11
A case of seizure activity after use of low dose bupropion
Sehoon Shim
Soonchunhyang Univ. Hospital, Psychiatry, Cheonan, Republic of Korea
Young-Joon Kwon, Hee-Yeon Jung, Seo-Young Kim, Ho-Joon Jang
Introduction: To report a case of seizure development in a patient with
major depressive disorder treated with NDRI (norepinephrine & dopamin
reuptake inhibitor) bupropion.
Method: A 19-year-old female with Depressed mood, feeling of worthlessness, recurrent suicidal ideation, diminished interest, and insomnia
was diagnosised for major depressive disorder, based on DSM-IV diagnostic criteria and hospitalized for the treatment of depression symptoms in
closed wards. Her Neurologic examination, Brain Computed Tomography,
and electroencephalogram(EEG) routinely taken at the time of admission
was normal. First she was prescribed with Mirtazapine 15mg orally daily.
then increased to 45mg. but symptoms improved partially, so bupropion
150mg a day was added. This combination therapy produced a significant
improvement in her symptoms. However, after 3 days of treatment, she
experienced a seizure without preictal event (auras) that started from the
legs and arms in a generalized tonic-clonic seizure feature. It lasted for a
minute and 40 seconds with only salivation but without tongue biting,
eyeball deviation, and urination. Postictal confusion was observed but
physical, neurologic, and EEG findings were normal. Considering many
case reports of bupropion induced seizures, we immediately discontiued
the usage of bupropion and started with a combination therapy of mirtazapine 45mg and venlafaxine 37.5mg. And then depressed symptoms
improved without seizure activity.
Results: This report is an example of the many case reports of bupropion
induced seizures, more interesting because of the low dosage of bupropion which induced seizures. Bupropion blocks reuptakes of dopamine
mainly also with blockage of norepinephrine and serotonin which is called
a NDRI that is effective for depression. Combimation therapy of SSRI and
191
bupropion seems to increase the antidepressant effect but is contraindicated in patients with a history of a head trauma, brain tumor, organic
mental syndrome and abnormalities in EEG and also in patients with alcohol withdrawal and sedatives withdrawal symptoms.
Conclusion: Low doses of bupropion can cause seizures even in patients
with no head trauma and normal EEG.
References: 1. Johnston JA, Lineberry CG, Ascher JA, et al. A 102-center
prospective study of seizure in association with bupropion. J Clin
Psychiatry. 1991; 52:450-456. 2. Van Wyck Fleet J, Manberg PJ, Miller LL,
et al. Overview of clinically significant adverse reactions to bupropion. J
Clin Psychiatry. 1983;44: 191-196.
P-17-12
Randomized trial of pharmacotherapy with telephone
monitoring to improve treatment of depression in primary
care in Santiago, Chile
Rosemarie Fritsch
Ricardo Araya, Jaime Solis, Elena Montt, Daniel Pilowsky, Graciela Rojas,
Manuel Fuentes
Introduction: Depression constitutes a public health problem due to its
high prevalence and its associated disability. Ministry of Health has made
important efforts to aboard this pathology. In order to improve the assistance of this disorder, a randomized clinical trial that compared a pharmacoterapeutic intervention controlled by phone from a central level (TM)
and the usual treatment (TH) was performed
Method: Sample: 345 women, average age of 37,4 (IC95%:36,6-38,1).
Age range was between 22 and 59 years. Women were blind evaluated
at 3 and 6 months with the HDRS and the SF-36 for rating depressive
simpthomathology and quality of life respectively.
Results: It both evaluations, improvement was significantly greater in the
TM group than the TH group. At 3 months evaluation improvement was
higher in TM group in the subscales of physical function, pain, general
health, energy, emotional role, mental health and standardized physical
and psychic scales of SF-36. At 6 months of treatment, this significant difference in favor of TM was maintained for energy, mental health and the
standardized psychic scale.
Conclusion: This clinical trial gives us evidence for simplifying and
improving interventions that are carried out in primary care.
References: 1. ARAYA R, ROJAS G, FRITSCH R, ACUNA J, LEWIS G.
Common mental disorders in Santiago, Chile: prevalence and socio
demographic correlates. Br J Psychiatry. 2001; 178:228-33 2. MURRAY
C, LOPEZ A. Alternative projections of mortality and disability by cause
1900 2020: Global Burden of Disease Study. Lancet. 1997;
349:1498504. 3. WHO. The WORLD HEALTH REPORT. Mental Health:
New Understanding, New Hope. World Health Organization 2001.
Switzerland. 2001. 4. BADAMGARAV E, WEINGARTEN S, HENNING J,
KNIGHT K, HASSELBLAD V, GANO A, et al. Effectiveness of Disease
Management Programs in depression: a systematic review. Am J
Psychiatry. 2003; 160:2080-2090. 5. SIMON G, VON KORFF M, RUTTER
C, WAGNER E. Randomised trial of monitoring, feedback, and management of care by telephone to improve treatment of depression in primary
care. BMJ. 2000; 320:550-4. 6. SIMON G, REVICKI D, VONKORFF M.
Telephone assessment of depression severity. J Psychiatr Res 1993;
27:247- 7. Hamilton M. A rating scale for depression. J Neurol Neurosurg
Psychiatry 1960; 23:56-62.
P-17-13
Assessment compliance to antidepressant drug by measuring plasma drug level
Michael Wong
Queen Mary Hospital, Psychiatry, Hong Kong, Peoples Republic of
Siu W. Tang, T Lee, Emily Chu
Introduction: Poor drug compliance may lead to relapse of depression
and may even be the real cause of treatment-resistance. The measurement of plasma antidepressant level may be more accurate than the
patients self report or the physicians own judgment of drug compliance.
192
Method: Patients age 18-65 on Citalopram/Escitaloproam were recruited

at public specialist psychiatric outpatient clinic and private clinic at community. At the day of study recruitment, 15 ml of blood sample is collected
by vacutainer. Plasma drug concentration assay is performed using high
performance liquid chromatography (HPLC) method. The treating physician completes a data collection form which capturing the subjects report
and the physicians estimate of drug compliance, clinical status, global
improvement of the psychiatric condition and the treatment regimen. The
subjects report and the physicians estimate on drug compliance are compared against the plasma drug level.
Results: Results show total unreliability of patients own report of drug
compliance and physicians judgment of patients compliance.
Conclusion: Patients report of compliance and treating physicians judgment of compliance are both unreliable. This might result in the erroneous impression of drug resistance resulting in unnecessary switching or
augmentation and false positive and false negative data in drug trials.
Measuring the plasma level of drug is not only of value in telling drug
compliance but also of great value before drug switching or augmentation. Measuring of drug level should be mandatory in clinical trials to
avoid inclusion of false response or non-response data.
References: Maddox, J. C., Levi, M., Thompson, C. (1994). The compliance with antidepressants in general practice. Journal of
Psychopharmacology 8, 48-53. Baumann, P., Hiemke, C., Ulrich, S.,
Gaertner, I., Gaertner, M. L., Rao, M. L., Eckermann, G., Gerlach, M.,
Kuss, H. J., Laux, G., Muller-Oerlingausen, B., Riederer, P., & Zernig, G.
(2004). Therapeutic monitoring of psychotropic drugs: An outline of the
AGNP-TDM Expert Group Consensus Guideline. Therapeutic Drug
Monitoring 26, 167-170.
P-17-14
Effect of stress during brain development on the forced
swimming behavior of barakol-treated rats
Sompop Sooampon
Introduction: Stress during brain development such as social isolation
rearing from weaning has been reported to alter the behavior of adult
animals and modify the responsibility to many psychotropic agents (1-3).
Barakol, 3a,4-dihydro-3a,8-dihydroxy-2,5-dimethyl-1,4-dioxaphenalene,
was isolated from the fresh young leaves of Cassia siamea, a plant used
in Thai traditional medicine. This compound has been reported to have
the anxiolytic and antidepressant properties (4). The aim of the present
experiment was to investigate the effect of social isolation rearing from
weaning on the forced swimming behavior in barakol-treated rats.
Method: Male Wistar rats were obtained from weaning, and housed
either alone (isolation rearing) or in groups of five-six rats/cage (social
rearing). Six weeks later, these rats were tested for their sensitivity to
barakol using the forced swimming test (5).
Results: The results demonstrated that the forced swimming behavior of
the saline-treated isolation reared rats was not significantly difference
from the socially reared controls. Sub-chronic administration of barakol (5
and 10 mg/kg i.p.) 24, 5 and 1 h to both isolation and socially reared rats,
significantly reduced the immobility time (antidepressant-like effect) and
increased struggling (P<0.05) compare with the saline treated isolation
reared rats. However, the antidepressant-like effect of barakol (5 and
10 mg/kg i.p.) was not observed in the socially reared rats.
Conclusion: These results indicate that stress during brain development
such as social isolation rearing alters the forced swimming behavior,
enhances the antidepressant-like effect in barakol-treated rats. Future
experiments will need to determine whether there are alterations of neurotransmitters in the central nervous system of the isolation stress rats.
Behav. Brain Res. 167: 232-236. 2. Wongwitdecha, N., Ngamnawakul,
B., Thaidee, H. and Soo-ampon, S. (2005) World J. Biol. Psychiat. 6
(Suppl.): 321. 3. Soo-ampon, S. and Wongwitdecha, N. (2002)
Pharmacologist 44(Suppl 1): A250. 4. Wongwitdecha, N., Soo-ampon, S.,
Ritilert, P. and Verawatanapakul, V. (2006) The International Journal of
Neuropsychopharmacology 9(Suppl 1): S67. 5. Porsolt et al., (1978) Eur J
Pharmacol 47, 379-391
P-17-15
Paroxetine in the treatment of depression and anxiety in
primary care
Rok Tavcar
Univ. Psychiatric Hospital, Ljubljana-Polje, Slovenia
Introduction: The first aim of this research was to increase the awareness
of primary care physicians to the whole spectrum of signs and symptoms
of depression which is often combined with anxiety. The second aim of
the study was to increase the knowledge of primary care physicians to
particular symptoms that need adjusted drug regime and appropriate
length of treatment. The third aim was to analyse treatment in the first
week of therapy.
Method: During the first visit the primary care physician recorded basic
information about a patient (gender, age), years of education (in our
country this index still reflects socio-economic status) and full description
of depression and anxiety symptoms using Hamilton depression scale
(HAM-D) and Hamilton anxiety scale (HAM-A). At the second visit questions about compliance, patients well-being, difficulties they have had in
the first week, additional questions they have about mental disorder or
antidepressants, and their willingness to continue the treatment. This visit
could be done also as a phone contact. The third visit included repeated
assessment of symptoms (HAM-D, HAM-A), assessment of treatment efficacy and further plans for treatment. The HAM-D and HAM-A total scores
were calculated. The therapy with the antidepressant paroxetine was documented since this drug is effective in anxiety and depressive symptoms.
The research was carried out in 60 centres across Slovenia.
Results: A total of 422 patients (mean age 49,8 14.23) with depression were included. HAM-D score at first visit was 23.2 and at the end of
the study it decreased to 10.2 (p<0.0001). The same was true for HAMA scores (18.9 vs. 8.3, p<0.0001).
Conclusion: Patients with higher rates of depression and anxiety symptoms at the beginning have had more additional questions and have more
often misinterpreted symptoms of mental disorder with side effects of
prescribed drug. Therefore we must provide them more information on
illness and medication side effects.
References: Kupfer DJ. Long term treatment of depression. J Clin
Psychiatry 1991; 5: Suppl 7: 28-34. Filteau MJ. Optimizing therapeutic
outcomes in the management of depression. Can J Diagnosis 2001; suppl
1: 1-8.
P-18
Psychopharmacology
P-18-01
Demystification of the fear of taking methylphenidate in
children with ADHD
Eunice Yuk Chun Wong
Lane Crawford House, Room 1408, Hong Kong, Peoples Republic of
Introduction: Although methylphenidate has been known over fifty
years in medicine, its usage in ADHD is still alarming not only to parents,
but to educators and even to physicians. It is striking that in Hong Kong
over 99% of ADHD children and adults have not been diagnosed or treated.
It is important to assess commonly worried side effects of the stimulant in
Hong Kong and to review positive outcome of treatment in order to
demystify the fear of the medication here.
Method: Out of the total number of clinic patients, 94 patients were
selected for the study. The inclusion criteria included age range from 6 to
18 years old; minimum five visits; treatment duration minimum of three
months. The exclusion criteria included patients who received other medications for co-morbidities. The retrieval of clinic data included socioeconomic data, the entry of data of each patients height, weight measured
in each visit; the complete sleep history, verbal report from the child, the
parent(s), and /or the teacher(s) about his/ her academic performance,
mood and socialization. For example, in review of academic performance,
the most recent test or examination results were documented and compared with previous results.
Results: The height, weight and sleep were found to be affected in the
initial period, but the adverse effects were found to be transient and they
became normalized after the initial period of time. On the other hand, the
positive outcome was found remarkable in academic performance,
improvement of mood, and socialization.
Conclusion: From the review of the treatment outcome of
methylphenidate on 94 ADHD clinic patients in Hong Kong, the widely
believed adverse side effects on growth and sleep were only transient. In
addition, the remarkably positive outcome of methylphenidate made the
medical treatment worthwhile as a starter of the comprehensive management plan, which included behavioral modification and training of learning skills.
P-18-02
The safety of topiramate in pregnancy
Salvatore Gentile
Asl salerno 1 operative, Unit n.4, Mental Health, Cava de Tirreni, Italy
Introduction: The reproductive safety of psychotropic drugs is becoming
a focus of growing interest, as several neuropsychiatric disorders are common in women in childbearing age. However, a paucity of studies have
been focused on topiramate, a new antiepileptic drug also effective in the
prophylactic treatment of migraine. Hence, aim of the study is to investigate the safety of topiramate in pregnancy and breastfeeding.
Methods: Computerized search via MEDLINE/Pubmed databases (19962006).
Results: Pregnancy. Treatment of pregnant mice, rats, and rabbits with
topiramate increases the rate of skeletal-craniofacial anomalies in the offspring.(1) Human data are summarized in Table 1.Breastfeeding. Limited
information suggests a free transfer of TPM into breast milk. The
Milk/Plasma ratio and the maternal weight-adjusted relative infant dose
ranges between 0.67 and 1.1 and from 3% to 23%, respectively. The
approximate absolute dose for infants ranges between 0.1 and
0.7 mg/kg/day. No adverse events were observed in 5 infants.(2) Table:
TABLE 1. Topiramate-induced fetal malformations and perinatal complications Study/Sample size (n)Malformations/ Peri-natal complications
Morrow, 2006 (35) 2 cases of fetal malformationsMorrell, 1996 (3)No
Vajda, 2003 (8)NoOhman, 2002 (5)NoCissoko, 2002 (1)1 case of neonatal distressVila Ceren, 2005 (1)1 case of fetal malformationsHoyme,1999
(1)1 case of fetal malformationsSee the Poster for the description of fetal
malformations
Conclusion: The teratogenic potential of the majority of the other old
and new antiepileptic drug is well-known.(3) Moreover, no conclusions
can be drawn about the reproductive safety of topiramate. Hence, there
is an urgent need for further data to be collected to estimate the safety
of the drug in pregnancy and lactation. Meanwhile, the use of topiramate in these female conditions should be taken into consideration only if
the expected benefits for the mother largely overweigh the unknown
potential risks for the fetus and newborn.
References: 1.Physicians Desk Reference, 2001. Montvale, NJ. Medical
Economics.2.Ohman I, Vitols S, Luef G, et al. Topiramate kinetics during
delivery, lactation and in the neonate: preliminary observations. Epilepsia
2002; 43 (10): 1157-60.3.Gentile S. Prophylactic treatment of bipolar disorder in pregnancy and breastfeeding: focus on emerging mood stabilizers. Bipolar Disord 2006; 8: 207-220.
P-18-03
Cognitive behavioural therapy for antipsychotic induced
weight gain: A preliminary randomized controlled trial
Yasser Khazaal
Emmanuelle Fresard, Anne Chatton
Introduction: Antipsychotic (AP) drugs frequently induce weight gain (1).
This phenomenon lacks current management, and, no previous controlled
studies seem to use cognitive therapy in order to modify eating and
weight related cognitions. Moreover, none of these studies consider outcome in terms of binge eating or eating and weight related
cognitions.The main aim of this study is to assess the effectiveness of a
cognitive and behavioural treatment (CBT) on eating and weight related
193
cognitions, binge eating symptomatology and weight loss in patients who

reported weight gain during an AP treatment.
Method: A randomized controlled study ( 12 weeks CBT vs. Brief nutritional education) was carried out on 61 patients treated by an antipsychotic and having reported weight gain following treatment. Binge eating symptomatology, eating and weight related cognitions, weight and
body mass index were assessed before treatment, at week 12 and 24.
Results: The CBT group improved on binge eating symptomatology, and
weight related cognitions whereas the control group did not. Weight loss
occured more progressively and was higher in the CBT group at week 24.
Conclusion: The proposed CBT treatment seems to be of particular interest for patients suffering from weight gain associated to an antipsychotic
treatment.
References: 1.Baptista,T., Kin,N.M., Beaulieu,S., and de Baptista, E.A.,
2002a. Obesity and related metabolic abnormalities during antipsychotic
drug administration: mechanisms, management and research perspectives. Pharmacopsychiatry. 35, 205-219.
P-18-04
Use of high doses of quetiapine in bipolar disorder
episodes are not linked to high activity of cytochrome
P4503A4 and/or cytochrome P4502D6
Yasser Khazaal
Chin Eap
Introduction: The use of quetiapine for treatment of bipolar disorders at
a higher dosage than the licensed range is not unusual in clinical practice.
Quetiapine is predominantly metabolised by cytochrome P450 3A4
(CYP3A4) and to a lesser extent by CYP2D6. The large interindividual variability of those isozyme activities could contribute to the variability
observed in quetiapine dosage.
Method: CYP3A4 activities were determined using the midazolam metabolic ratio (1,2) in 21 bipolar and schizoaffective bipolar patients genotyped for CYP2D6. 9 patients were treated with a high quetiapine dosage
and 11 with a normal quetiapine dosage.
Results: One patient in the high dose and one patient in the normal dose
groups were genotyped as CYP2D6 ultrarapid metabolizers. CYP3A4
activities were not significantly different between the two groups, with
even a trend for a higher CYP3A4 activity in the normal dose group as
compared to the high dose group (midazolam metabolic ratio: 9.4 8.2;
6.2; 1.7-26.8 versus 3.9 2.3 ; 3.8; 1.5-7.6, respectively, p = 0.06).
Conclusion: The use of high quetiapine dosage for the patients included
in the present study cannot be explained by variations in pharmacokinetics parameters such as a high activity of CYP3A4 and/or of CYP2D6.
References: 1.Eap CB, Buclin T, Cucchia G, et al. Oral administration of
a low dose of midazolam (75 microg) as an in vivo probe for CYP3A activity. Eur J Clin Pharmacol 2004;60:237-246 2.Eap CB, Bouchoux G, Powell
GK, Baumann P. Determination of picogram levels of midazolam, and
1- and 4-hydroxymidazolam in human plasma by gas chromatographynegative chemical ionization-mass spectrometry. J Chromatogr B Analyt
Technol Biomed Life Sci 2004;802:339-345
P-18-05
Switching to olanzapine among adolescents with schizophrenia nonresponsive to risperidone: An open trail
Evgeny Koren
Moscow Research Institute of Psychiatry, Moscow, Russia
Introduction: Based on chemical structure differences, it was hypothesized that the two compounds would show distinct efficacy in treatment of adolescents with schizophrenia. Published experience of switching with newer atypical antipsychotics is still lacking in this age range Use
of olanzapine in adolescent age not yet officially permitted in Russia and
risperidone allowed only from 15 years.
Method: To test this hypothesis, inpatient and outpatient adolescents
(mean age 16,2 years) with ICD-10 schizophrenia (N=12) currently unsuccessfully treated with risperidone were switched to olanzapine (initial
dose 5 mg/day, mean dose 13,4 mg/day) for 8 week. The primary efficacy
variable was baseline to end point change in PANSS and CGI score.
194
Results: Dropped out 2 patients due with intolerability and adverse

events (somnolence and weight gain) and 10 patients (83,3%) completed
the full trial. Responder rate (at least 20% decrease in PANSS total score
and final CGI of 3 or less) was 66,7%. On average, the total scores of
PANSS were reduced from baseline to endpoint by 36.9% (p<0,05) after
8 weeks of olanzapine therapy. These clinical improvements occurred
across a broad range of symptom domains and especially included reductions in positive, negative and general psychopathology subscores.
Weight gain occurred in significantly greater proportion of patients and
no incidents of extrapyramidal side effects were reported.
Conclusion: These findings support the efficacy of the switching to olanzapine due with unsuccessful treatment of risperidone and could be one
of the treatment strategy in this population. However, differential preclinical profiles of this two drugs need to be also evident in a controlled clinical investigations.
P-18-06
Taurine: Stabilizer of membranes and hydrotropic substance. Its application in neuropsychiatric disorders and
aging
Iris Lieber
Argentina
Aaron Epelbaum
Introduction: Purpose We suggest the implementation of Taurine,amino
2 - ethan sulphonic acid, for the prevention and treatment in patients that
are with aging and for neuro - psychiatric disorders. It increases the vitality, immunity, acts as osmotic regulator ,as an inhibitory neurotransmitter
and modulator, hydrotropic, tension active substance and as stabilizer of
membranes. Considerations: Taurine is a conditional natural essential
amino acid .It is found in abundance in the liver, heart muscle, retina, the
brain, pituitary gland,, hypothalamus, pineal gland, olfactory bulb, in the
central nervous system, platelets and leukocytes We consider that it participates in the psychoneuroinmunoendocrinological PNIE system.
Taurine which is found naturally in bile salts, as taurocholate, it is a
hydrotropic and tensioactive substance which facilitates the emulsification of fats. Hydrotropy refers to the significant increase in the solubility
of poorly soluble substances, with the presence of an hydrotropic substances ,maintaining in solution all the elements ,even in a reduced volume of water making the blood less viscose, more fluid. In this way would
prevent the deposit of insoluble substances such cholesterol esters, lipids
in atherosclerosis and beta amyloid in Alzheimer disease and in aging.
Taurine is an inhibitory neurotransmitter and stabilizer of membranes,
therefore could be used where there is an excess of excitability or alteration in the membranes, to counteract and balance the excitatory amino
acids such as glutamate and aspartate. It would be useful in aging where
there is less synthesis of taurine, in hypomania, anxiety, bipolar disorders
and in epilepsy. Clinical Experiences: We realized a preliminary clinical
experience administering as adjuvant taurine in patients suffering from
bipolar disorder, comparing with patients taking placebo. According to a
daily diary and with the evaluation with Hamilton Scale, we saw a reduction in their symptom,with a stabilization of mood without adverse
reactions.
Conclusion: We consider that the supplementation of taurine could be
useful for the elderly, and for prevention and treatment of neuro -psychiatric disorders, because of its multiple functions.
References: Lieber I.I. Hydrotropy in Medicine? Semana M dica 1
23,18l0-18l6,1963 Lieber I.I.,Epelbaum A, Epelbaum C.A.,Epelbaum
D.M. Hydrotropy as a factor of prevention and treatment in brain atherosclerosis and Alzheimer disease Argentine Journal of Psychiatric
Biology XI,81,12-24, 2004-
P-18-07
Omeprazole-induced delirium
Dimos Dimellis
Maxima SA, Kalamaria Thessalonikis, Greece
Dimitris Mpalaskas, Nikos Kofidis
Introduction: Omeprazole is a commonly used proton pump inhibitor
with rarely reported psychiatric adverse effects. Current literature contains
only one other case-report of omeprazole-induced delirium.
Method: We present the case of a 33-year old (actively) schizoprenic
patient who while on an antipsychotic regimen (amisulpride), received
omeprazole.
Results: The day after, the patient presented with confusion, daytime
sleepiness, disorientation to time and place (especially near bedtime) and
disorganised behaviour. Laboratory tests and neurological clinical evaluation were normal. Two days later we discontinued omeprazole and on
the third day Mr A was alert and orientated with good attention and concentration.
Conclusion: Omeprazole-induced delirium has been previously reported
by Heckmann et al (Heckmann et al, 2000). As far as we know, our case
is the first report of delirium that occurred to a psychotic patient during
active schizophrenic phase, while receiving omeprazole. There is no bibliographical support for possible pharmacokinetic or pharmakodynamic
interactions between haloperidol, amisulpride, biperiden and omeprazole. Other organic or functional causes contributing to mental status
alterations were excluded. Moreover, the delirium started and subsided in
relation to omeprazoles introduction and discontinuation implicating a
temporal and possible etiological relation between omeprazole and delirium. Although we are not able to propose the underlining mechanism we
suggest extra cau-tion when administering omeprazole to actively psychotic patients already receiving antipsychotic treatment.
References: Heckmann JC, Birklein F, Neundorfer B (2000) Omeprazoleinduced delirium. J Neu-rol. Jan; 247 (1):56-7
P-18-08
Pregabalin in Geriatric Psychiatry
Wolfgang Wittgens
VKKD, Dep. of Geriatric Psychiatry, Meerbusch, Germany
M. Schreiber
Introduction: The goal of our katamnestic study was to examine efficacy,
tolerability and dose range of Pregabalin given as mood stabilizer to aged
psychiatric patients.
Method: During one year we treated 38 aged patients with Pregabalin
because of affective symptoms in depression, anxiety disorders or dementia.
Nearly all patients showed a high comorbidity with internal diseases and
had a complex comedication. The age ranged between 66 and 94 years
(mean: 78,6 years), male: 8, female: 30. The dose ranged from 25 to
300 mg (mean: 121,05 mg). Excepting a mild dizziness we didnt notice
any side effects. Especially with regard to the renal elimination of
Pregabalin no interaction of drugs could be found. Pregabalin was effective even in low dose to the leading affective symptoms.
Conclusion: As a result of study we think that Pregabalin is also effective
in affective symptoms of geriatric psychiatric patients, well tolerable and
unproblematic with regard to the interaction of drugs which is all-important in the treatment of aged patients.
P-18-09
Trazodone as prophylactic treatment of classic migraine in
a patient with bipolar disorder and epilepsy: Systematic
review and a case report
Vitor Hugo Sambati Oliva
Federal University of Parana, Dept. of Psychiatry, Curitiba, Brazil
Cristiano Alvarez, Osmar Ratzke
Introduction: Some scientific data have shown a high prevalence of
migraine in patients with bipolar disorder. Considering the severity of
these diseases, the current study aims are: 1) accomplishing a systematic
review about Trazodone (TZD) for prophylaxis of classic migraine in adults
with bipolar disorder and epilepsy; 2) illustrating its effect with a case
report.
Method: Methods and results: We searched MEDLINE and the main term
has been Trazodone in combination with bipolar disorder, migraine and
epilepsy. From 28 selected articles, none has approached TZD for prophylaxis of migraine in adults and only 7 studies have considered this action
in children and adolescents. Among the latter, there was one study in
favor of TZD, two against it and two with inconclusive results. However,
TZD showed efficacy in the following case: a 43-year-old woman has
received the diagnosis of recurrent depressive disorder since her adolescence. She has been in a current depressive episode, severe without psychotic symptoms for 4 years. She has had 3 suicide attempts, besides classic migraine, corioretinome cicatrix and hypothyroidism. Although
Fluoxetine and Clonazepam use, there was no improvement. Moreover,
syncope, increased generalized irritability and persistence of headache
appeared. After important electroencephalogram changes were noticed,
preliminary diagnosis of epilepsy was made and Valproic Acid was initiated. Depressive symptoms have persisted and the patient became very irritable and agitated. Therefore, bipolar spectrum was considered and confirmed by no suicide self agression crisis throughout the follow-up. Thus,
the treatment has aimed at 4 effects: anticonvulsivant, antimigrainous,
mood stabiliser and antidepressant. In that case, Lithium, Carbamazepine, Topiramate, Propranolol and Sertraline were unsuccessfully
tried in therapeutic doses. Anticonvulsivant and mood stabiliser effects
were achieved with Valproic Acid. In order to have antimigrainous and
antidepressant actions, TZD was prescribed at therapeutic dose.
Conclusion: Despite the missing data from the literature about this
effect, we noticed that TZD was effective in the current case not only in
the treatment of a depressive episode of bipolar disorder but also in prophylaxis of classic migraine. Finally, we suggest further studies to sustain
or not these findings.
References: Headache. 1993 Jan;33(1):36-9. Cephalalgia. 2006
May;26(5):497-505. Cochrane Database Syst Rev. 2003;(4):CD002761.
Neurology. 2004 Dec 28;63(12):2215-24. Paediatr Drugs. 1999 JanMar;1(1):7-18. Br J Psychiatry. 1991 Feb;158:275-8. J Affect Disord. 1990
Apr;18(4):253-7.
P-18-10
Trends in sedative-hypnotic drugs prescription in Croatia
from 2001 to 2005
Dinko Vitezic
Univ. of Rijeka Medical School, Clinical Pharmacology, Croatia
V. Matkovic, T. Buble, D. Ljubicic, V. Dordevic, J. Mrsic Pelcic, G. Zupan,
A. Simonic
Introduction: The aim of this study is to analyze the trends in prescription of sedative-hypnotic drugs in Croatia during the five-year period.
Method: The information data on sedative-hypnotic drugs utilization for
the period 2001-2005 were obtained from the Croatian National Health
Insurance Company. According to WHO Collaborating Centre for Drug
Statistics Methodology, the drug utilization data are presented in defined
daily doses/1000 inhabitants/day (DDD/1000/day).
Results: During the investigated period sedative-hypnotic drugs utilization increases from 29.76 DDD/1000/day in the year 2001 to 50.33 (69%
increase) in the year 2005. The most widely used sedative-hypnotic drug
in Croatia was diazepam (five-years average 12.99), followed by
oxazepam (9.14), alprazolam (8.47), lorazepam (4.62), zolpidem (2.86)
and nitrazepam (2.64). There is significant increase for the diazepam
(from 8.56 in 2001 to 15.85 in 2005), alprazolam (from 4.48 to 12.19),
and zolpidem (from 0.6 to 5.67), while there was decrease in utilization
of oxazepam (9.53 to 8.34). The usage of nitrazepam, meprobamate and
clonazepam was low and remains steady during the investigated period.
Conclusion: During the five-year period there was a considerable
increase in prescription of all sedative-hypnotic drugs. According to these
results the educational efforts, information campaigns and therapeutic
rationalization should be implemented in Croatia in the following years in
order to slow down sedative-hypnotic drugs usage. There is also obvious
need for more complex research in order to investigate reasons for this
drug utilization increase.
195
P-18-11
Atomoxetin as a treatment option for attention deficit/
hyperactivity disorder (adhd) and comorbid addiction
Martin Ohlmeier
Hannover Medical School, Psychiatry and Psychotherap., Germany
B. T. e. Wildt, M. Ziegenbein, H. M. Emrich, N. Buddensiek
Introduction: Attention deficit/hyperactivity disorder (ADHD) is a common affliction in adults with a 2-4% prevalency. Several studies reported
a 3-4 fold increased prevalency for alcohol and drug addiction among
ADHD patients. Due to the supposed addictive potential of the amphetamine derivative methylphenidate, there are controversial discussions concerning the treatment of ADHD using drugs, particularly in the therapy of
comorbid addiction. Just recently, a possible alternative has been made
available for the treatment of ADHD in infancy in the form of a noradrenergic receptive inhibitor, atomoxetin.
Method: Four young adult male ADHD patients presenting with comorbid addiction (alcohol, cannabis and/or cocaine) underwent a detoxification programme. Atomoxetin was then administered according to the
individuals requirement. The dosage was gradually increased. Clinical follow-ups and examinations were carried out using the Brown ADD Scales.
Results: Even with the initial dosage of 18mg/die the patients reported
improvement of their ADHD symptoms. This was also confirmed by the
Brown ADD Scales. An increase in dosage of 40-80mg/die resulted in further clinical improvement. The patients complained initially of side effects
such as dizziness, nausea and increased sweating but these symptoms
regressed after a while. Three patients demonstrated considerable
improvement and one patient only moderate change in the intrinsic
symptoms of ADHD.
Conclusion: The results of various studies on the effect of atomoxetin on
adult ADHD patients were in accordance with our own study. Several
patients were found to benefit from this treatment. No alcohol or drugs
were consumed whilst under therapy with atomoxetin and this, in turn,
had a positive effect on the addiction itself. It also demonstrates that several ADHD patients turn to drugs and/or alcohol as a form of self therapy.
Atomoxetin is now recognized as an effective therapy option in the treatment of ADHD and comorbid addiction. It is essential to administer the
correct dosage for each individual patient in order to avoid any unwanted
side effects.
References: Heil SH, Holmes HW, Bickel WK, Higgins ST, Badger GJ, Laws
HF, Faries DE. Comparison of the subjective, physiological, and psychomotor
effects of atomoxetine and methylphenidate in light drug users. Drug and
Alcohol Dependence 67, 2002, 149-156. Michelson D,Adler L, Spencer T,
Reimherr FW, West SA, Allen AJ, Kelsey D, Wernicke J, Dietrich A,Milton
D. Atomoxetine in adults with ADHS: two randomized, Placebo-controlled studies. Biological Psychiatr. 53, 2003, 112-120. Ohlmeier M,
Peters K, Buddensiek N, Seifert J,teWildt B, Emrich HM, Schneider U.
ADHS und Sucht. Psychoneuro 31, 2005, 554-562.
P-18-12
The evaluation of Analgesics use (and abuse) in patients
with haemophilia
Bojana Avgustin
University Psyhiatric Hospital, Ljubljana, Slovenia
Zdenka Cebasek Travnik, Brigita Novak Sarotar
Introduction: Haemophilia is a life threatening, life long condition
caused by absence of or defective coagulation factors. People with
haemophilia tend to bleed internally into joints and muscles, which can
lead to pain. Pain is a distressing symptom that can affect people with
haemophilia in a number of ways. A bleed into a joint can cause acute,
severe pain whereas the long-term effects of recurrent bleeds can lead to
chronic and disabling symptoms. People with haemophilia use different
types of analgesics for pain relief. On the other hand, patients with
haemophilia need to manage psychological pain, too. A high percentage
of hemophiliac patients suffer from different psychological problems,
most common anxiety, depression and somatization disorders. Physical
and psychological pain need to be differentiated and assessed correctly in
order to be managed properly.
196
Method: According to our clinical experiences, several patients with

haemophilia were abusing analgesics to reduce and control co-morbid
anxiety or depression.
Results: Aim of our study is to evaluate the use of analgesics in patients
with haemophilia. We will evaluate the medical records of 180 patients
with haemophilia from Slovenian Haemophilia society and search for type
of analgesics, indications for their prescription and potential complications: physical and psychiatric side effects (overdoses, analgetic abuse or
misuse according to the DSM - IV criteria. The pattern of the analgetic use
will be compared to the results of the quality of life questionnaire and
functional parameters of the large joints.
Conclusion: Will be presented at the conference.
References: Canclini M, Saviolo-Negrin N, Zanon E, Bertoletti R, Girolami
A, Pagnan A. Psychological aspects and coping in haemophilic patients: a
case-control study. Haemophilia 2003; 9:619-624. Elander J, Barry T.
Analgesic use and pain coping among patients with haemophilia.
Haemophilia 2003; 9: 202-213. Fakhari A, Dolatkhah R. Psychiatric disorders in Haemophilic patients. Haematol 2004; 26:243-51. American
Psychiatric Association. Diagnostic and statistical manual of mental disorders, 4 rd Ed, Washington, DC: American Psychiatric Press, 1994. Dersh
J, Polatin PB, Gatcel RJ. Chronic pain and psychopathology: research findings and theoretical considerations. Psychosom Med. 2002; 64: 773-786.
Patt S, McDiarmid T. Tramadol addiction. J Fam Pract 2005;54:356.
P-18-13
Double blind trial of amantadine and haloperidol for treatment of delirium
Hanyong Jung
Soonchunhyang University, Neuropsychiatry, Bucheon-Si, Gyeonggi-Do,
Republic of Korea
Kim Yangrae, Lee Soyoung
Introduction: The purpose of this study is to compare the clinical efficacy
of amantadine with haloperidol in the treatment of delirium.
Method: 19 patients with delirium were randomly assigned to receive a
flexible-dose regimen over 7days. The 10 subjects received amantadine
while the other 9 received haloperidol. The delirium rating scale (DRS) was
used as a specific tool to rate the severity of delirium. The neurobehavioral rating scale (NRS) was used for psychiatric and behavioral symptoms.
MMSE-K (mini-mental status examination Korea version) was used to rate
the cognitive functions. One psychiatrist, blind to the status of treatment,
measured the changes of symptoms at the baseline, and on the third and
seventh day after starting medication.
Results: There were no significant differences in the mean baseline scores
of DRS, NRS and MMSE-K between the haloperidol group and the amantadine group. Compared with the baseline (mean=9.83, SD=5.49),
MMSE-K score of the amantadine group significantly improved (t=-2.69,
p=.043) on the seventh day (mean=15.33, SD=4.84). In addition, the NRS
score of the amantadine group also exhibited a tendency (t=2.17,
p=.082) to improve on the seventh day (mean=26.67, SD=8.89), compared with the baseline (mean=47.00, SD=22.30). In the haloperidol
group, the DRS scores were decreased significantly (t=2.90, p=.027;
t=3.69, p=.010) on the third (mean=14.29, SD=7.74) and seventh day
(mean=12.29, SD=8.28), compared with the baseline (mean=17.14,
SD=6.15). Likewise, the MMSE-K scores were significantly improved (t=2.99, p=.024; t=-2.46, p=.049) on the third (mean=12.71, SD=10.14)
and seventh day (mean=15.29, SD=11.53), compared with the baseline
(mean=10.29, SD=8.81). In addition, The NRS scores showed a tendency
to improve (t=2.41, p=.053; t=2.24, p=.066) on the third (mean=43.29,
SD=23.73) and seventh (mean=41.29, SD=26.98) day, compared with the
baseline (mean=51.14, SD=17.91).
Conclusion: Haloperidol group showed significant difference in DRS and
MMSE-K scores and amantadine group showed improvement in NRS and
MMSE-K scores. But there was no significant difference between those
two groups in comparation of the effects. Likewise, it can be suggested
that each medication has its own property and different effects on symptoms.
P-28
Psychopharmacology II
P-28-01
Serotonin transporter polymorphism and fluoxetine effect
on impulsivity and aggression in borderline personality
disorder (*).(*) Proyecto FONDECYT N 1030307
Hernan Silva
Patricia Iturra, Aldo Solari, Juana Villarroel, Sonia Jerez, Wilson Vielma,
Cristian Montes, Lorena Pumarino, Natalia Roa
Introduction: In depressive patients short (S) allele of the serotonin transporter promoter gene (5-HTTLPR) predicts a poorer response to selective
serotonin reuptake inhibitors (SSRI). The purpose of this work is to study
those polymorphisms in order to predict SSRI anti-aggressive and antiimpulsive effect in borderline personality disorder patients.
Method: 59 borderline personality disordered patients according to the
International Personality Disorder (IPDE) for DSM-IV and without axis I disorders were treated for 12 weeks with flexible doses of fluoxetine. All
subjects were evaluated with Overt Aggression Scale Modified (OAS-M)
at the entry and 2, 4, 8 and 12 weeks of treatment. L and S polymorphisms of the serotonin transporter promoter were determined.
Fluoxetine response was compared for LL versus S carriers (LS+SS).
Statistical analysis was performed using the Statistical Package for the
Social Sciences (SPSS).
Results: The reduction of OAS-M total scores and of the Aggression and
Irritability components scores shows a better response to fluoxetine in
LL carriers than in S carriers.
Conclusion: Similarly to depressive patients L carriers have better
response to fluoxetine than S carriers. S allele may be a common factor
of poor response to SSRI in disorders related to a serotonergic dysfunction.
References: 1- Lesch KP, Bengel D, Heils A, Sabol SZ et al. Association of
anxiety-related traits with a polymorphism in the serotonin transporter
gene regulatory region. Science 1996;274:1527-31 2- Lesch KP,
Gutknecht L. Pharmacogenetics of the serotonin transporter. Prog
Neuropsychopharmacol Biol Psychiatry 2005;29(6):1062-1073. 3- Kim
DK, Lim SW, Lee S, Sohn SE, Kim S, Hahn CG, Carroll BJ. Serotonin transporter gene polymorphism and antidepressant response. Neuroreport
2000;11(1):215-219. 4- Serretti A, Benedetti F, Zanardi R, Smeraldi E. The
influence of Serotonin Transporter Promoter Polymorphism (SERTPR) and
other polymorphisms of the serotonin pathway on the efficacy of antidepressant treatments. Prog Neuropsychopharmacol Biol Psychiatry
2005;29(6):1074-1084
P-28-02
A randomized, double-blind, comparison of sertraline with
early alprazolam xr co-administration vs sertraline/placebo
for panic disorder: Preliminary data
Andrew Goddard
Indiana University, Psychiatry, Indianapolis, USA
Elizabeth Hay, Anantha Shekhar, Karl Rickels, David Sheehan
Introduction: Several studies have suggested the early clinical benefit
and tolerability of brief benzodiazepine (BZD) co-administration with the
SSRI therapy for the stabilization treatment of acute panic disorder (PD)
(Goddard et al., 2001)(Pollack et al., 2003). In order to retest these initial
results, and enhance their generalizability, we are conducting a SSRI/BZD
treatment study, involving 3 sites, with the aim of enrolling 150 PD
patients with multiple psychiatric and medical co-morbidities.
Method: Patients have a current principal DSM-IV diagnosis of PD confirmed by MINI interview. They receive open-label, flexible-dose sertraline
for 12 weeks (target dose=150 mg/d; range 25-200 mg/d), and, in addition, are randomized to either active alprazolam XR for 4 weeks (flexibledosing; target dose 3 mg/d, range 1-4 mg/d) or matching placebo (PLAC)
tabs. Alprazolam XR/PLAC is then tapered over 3 weeks and discontinued. The PDSS scale (Shear et al., 1997)(scoring range 0-28) is one of the
primary efficacy measures. Study data are captured in real time using
direct data entry into a tablet PC. A follow-up visit is performed 3 months
after completion of the acute 12-week trial.

Results: 63 patients have been randomized to study treatment thus far
(meanSD total PDSS score at baseline=14.04.3). 23/63 patients (36%)
were early withdrawals from the acute trial, with 8 of these dropping out
due to adverse events. 40 patients completed week 12 and were significantly improved from baseline (meanSD total PDSS score at wk
12=4.54.6)(paired t-test t=9.3, df,39, P<0.0001-blinded pooled data).
27/63 patients (43%) came back for the 3-month follow-up visit
(meanSD total PDSS score=3.53.7). Inspection of aggregate PWC
mean scores by visit did not reveal dramatic increases in scores during BZD
tapering.
Conclusion: Patients are generally making expectable clinical improvements during the course of the study with the regimens used. The 3-week
BZD tapering schedule appears to be well tolerated.
References: Goddard A W; Brouette T; Almai A; Jetty P; Woods S W;
Charney D. Early co-administration of clonazepam with sertraline for
panic disorder. Archives of General Psychiatry, 58, 681-686, 2001.
Pollack MH, Simon NM, Worthington JJ, Doyle AL, Peters P, Toshkov F,
Otto MW. Combined paroxetine and clonazepam treatment strategies
compared to paroxetine monotherapy for panic disorder. J
Psychopharmacology, 17(3) 276-282, 2003.
P-28-03
Acute neuroendocrine response to IV citalopram and treatment response in OCD
Fabio Corregiari
Instituto de Psiquiatria, Amban, Sao Paulo, Brazil
Wagner Gattaz, Marcio Bernik
Introduction: Serotonergic pharmacological challenges have failed to
produce consensual results in patients with OCD diagnosis, suggesting a
heterogeneous 5-HT activity in this disorder.The aim of the present study
was to compare the neuroendocrine response to a serotonergic challenge
in serotonin reuptake inhibitors treatment resistant and responsive OCD
patients and healthy volunteers.
Method: Thirty OCD treatment resistant patients, thirty responsive and
30 controls paired for sex and age were included. Each subject received
20 mg of IV citalopram. Prolactin, cortisol and GH plasma concentration
were measured at times - 20, 0, 20, 40, 60, 80, 100, 120, 140 and 160
minutes after the onset of citalopram infusion.
Results: Citalopram did not induce OCD symptoms in patients. The drug
induced a larger peek of prolactin in control group (max%=65.76
105.1) than in resistant (max%=17.41 31.06) and responsive groups
(max%=15.87 31.71; p=0.032; Friedman qui2=6.87; df=2). However,
the cortisol response did not differ between Control and Responsive
groups and was attenuated in the treatment resistant group (RT
max%=20.98 58.14 versus RP max%= 47.69 66.94; CN max%=
63.58 88.4; p=0.015; Friedman qui2=8.60; df=2).
Conclusion: We concluded that either treatment resistant or responsive
patients have blunted prolactin response to citalopram, but only resistant
patients also show an attenuated cortisol response, suggesting a more
disrupted central serotonergic transmission in this group.
P-28-04
Platelet serotonin concentration and behavioral therapy
response in obsessive-compulsive disorder
Thiago Sampaio
Instituto de Psiquiatria, Amban, So Paulo, Brazil
Cristiane Pinheiro, Fabio Corregiari, Mrcio Bernik
Introduction: Serotonin reuptake inhibitors and behavioral therapy with
exposure and response prevention [ERP]) are similarly effective for OCD.
Studies have demonstrated similar neurobiological changes eliciated by
these different treatments in OCD patients, suggesting that ERP could
involve serotonergic mechanisms. Platelet 5HT concentration is a representative measure of central serotonergic system used as a biological
marker of the synaptic transmition.The aim of this study was to compare
the platelet 5HT concentration (basal and variation in 8 weeks of ERP)
among responders and non-responders, as well as among adherent and
non-adherent patients.
197
Method: 27 OCD patients were included and submitted to a 16 weeks

ERP standard protocol. The basal and final (after 8 weeks) platelet 5HT
concentrations were dosed and the clinical response measured by YBOCS.
Results: There were higher basal concentration and reduction in 8 weeks
of platelet 5HT concentration in the responders group compared with
non-responders and higher basal platelet 5HT concentration in adherents
compared with non-adherents. Nevertheles, any one of this differences
was significant (p>0,05).
Conclusion: In the studied sample the platelet 5HT concentration did not
predict the clinical response or adherence to ERP, and there wasnt relationship between the platelet 5HT variation and the clinical response to
ERP.
P-28-05
Treatment resistant obsessive-compulsive disorder:
An investigation of co morbid personality disorders
Cristina Rosenthal
Instituto de Psiquiatria, Amban, So Paulo, Brazil
Mrcio Bernik, Fabio Corregiari
Introduction: There is limited experience reported in the literature about
the influence of personality disorders on the treatment response of subjects with obsessive-compulsive disorder (OCD). Jenike et al(1986) verified
that a subgroup of patients resistant to conventional treatment met the
diagnostic criteria for schizotypal personality disorder. Baer & Jenike
(1992) suggested that the subjects who are comorbid for any of the personality disorders in Cluster A - which comprise Paranoid, Schizoid, and
Schizotypal Personality PDs - have a worse prognostic. In previous
research, applying the Structured Interview for DSM-III Axis II Personality
Disorders (SIPD-R). Subsequent findings have shown that the totality of
the cases met the criteria for at least one PD, predominantly from cluster C,
which includes obsessive-compulsive personality disorder (OCPD),
dependent and avoiding PDs.
Method: This study presents findings from a sample of ten adult subjects
with treatment-resistant OCD. The inclusion criteria were: at least 6 years
of diagnostic and treatment of the disease; a Yale-Brown ObsessiveCompulsive Scale (Y-BOCS) score of >= 20; and a (1994) DSM-IV Axis V
Global Assessment of Functioning (GAF) score >=50. To investigate the
personality disorders, the Structured Interview for Personality Disorders as
defined by DSM III-R was used.
Results: The final results showed the most prevalent PDs were from cluster
C (84, 22% of the subjects), followed by cluster A (19,52% of the subjects)
and to a lesser degree, cluster B (5,26% dos cases), which includes the diagnoses of anti-social, borderline, histrionic, and narcissistic PDs.
Conclusion: The most prevalent PDs among patients with treatment
resistant OCD were from cluster C, followed by cluster A personality disorders.
References: Baer L, Jenike MA. Personality disorders in obsessive compulsive disorder. Psychiatr Clin North Am. 1992 Dec;15(4):803-12. Jenike
MA, Baer L, Minichiello WE, Schwartz CE, Carey RJ Jr. Coexistent obsessive-compulsive disorder and schizotypal personality disorder: a poor
prognostic indicator. Arch Gen Psychiatry. 1986;43(3):296.
P-28-06
Transition from immediate-release methylphenidate (irmph) to extended-release methylphenidate improves quality of life of patients with adhd - results from a naturalistic study (42603-att-4001)
Ludger Hargarter
Martin Gerwe, Joerg Czekalla, Fritz Mattejat
Introduction: To investigate the effectiveness, tolerability, functionality
and quality of life (QoL) under naturalistic conditions of once daily extended
release methylphenidate (OROS-MPH - CONCERTA) in children and
adolescents with attention-deficit/hyperactivity-disorder (ADHD), who
had previously been treated with IR-MPH.
Method: Interim analysis of an open-label, prospective, multicenter
observational study (42603-ATT-4001)in children and adolescents aged
6-18 years with ADHD (DSM-VI). After transition patients were treated
198
with OROS-MPH in flexible doses for 3 months. Primary documentation

parameters were change in IOWA Conners parent rating scale, C-GAS,
and inventory for the assessment of quality of life (ILK). Statistical analyses based on ITT population (LOCF, Wilcoxon-test for dependent samples).
Results: Data from 296 patients (mean age 10.42.5 years; 85% male)
were documented with 85% completing the study. There was a marked
reduction in symptomatology from 2911 to 1911 points at endpoint
on the IOWA Connors parents rating scale (p<0.0001). QoL significantly
improved from 174 to 204 points on the ILK parent rating scale
(p<0.0001). Functionality showed a significant improvement of 1214
points in C-GAS (p<0.0001). 19.3% of the patients had at least one
adverse event (AE). In 2 patients serious AE were documented and were
rated as unrelated to OROS-MPH. Most frequent AEs were insomnia
(5.7%) and nervousness (2.7%). Quality of sleep and appetite of the
patients did not change after transition to OROS-MPH. Tolerability was
rated as good or very good by 85% of the parents.
Conclusion: In this naturalistic study the transition to OROS-MPH led to
a significant improvement in clinical symptomatology, functionality and
quality of life in patients with ADHD pretreated with IR-MPH. Treatment
with OROS-MPH showed to be safe and well tolerated.
P-28-07
Early life stress increases the effect of valproic acid on the
rat elevated plus maze
Introduction: Early life stress e.g. social isolation rearing from weaning
may alter the behaviors and the neurochemical properties of the adult
animals and modifies the responsibility to many psychotropic agents (1-3).
The aims of the present experiments were to investigate the effect of
early life stress on anxiety using the rat elevated plus-maze, and to compare the effect of valproic acid on the plus-maze behaviors in rats reared
with different stress conditions.
Method: Male Wistar rats obtained at 21 days of age and housed either
in groups of five rats/cage (social rearing) or singly (isolation rearing) for
five weeks. These rats were placed individually onto the elevated plusmaze following intraperitoneal injection of saline or valproic acid (100
and 400 mg/kg) 30 min before a 5 min test.
Results: The results demonstrated that social isolation rearing had no
marked effect on the rat elevated plus-maze behavior. Pretreatment with
valproic acid (100 and 400 mg/kg i.p.) produced a dose related anxiolytic
effect in both socially and isolation reared rats. This effect was indicated
by increasing in the percentage of open:total arm entries and time, and
significantly increase in time spent and the number of the end of open
arm entries (P< 0.05) on the elevated plus-maze. These anxiolytic profiles
of valproic acid were more pronounced in isolation reared rats.
Conclusion: The present results show that early life stress such as social
isolation rearing from weaning enhances the anxiolytic effect of valproic
acid in the adult rats. This abnormality may reflect alterations in central
neurotransmitters such as GABA and glutamate etc.
Behav. Brain Res. 167: 232-236. 2. Wongwitdecha, N. and Marsden, C.A.
(1996) Brain Res., 715, 119-124. 3. Wongwitdecha, N., and Marsden,
C.A. (1996) Behav. Brain Res., 75, 27-32.
P-28-08
Influence of rearing conditions on the anxiolytic profile of
nitric oxide synthase inhibitor, l-name
Introduction: Rearing conditions during the early stage of life have been
known to exert effects on animals emotionality, behavioral difference
and responsively to several psychoactive drugs (1-5). The purpose of the
present experiments was to investigate the influence of rearing conditions
on the anxiolytic profile of nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) in the adult rats.
Method: Male Wistar rats were obtained at 21 days of age and reared
either alone (isolation rearing) or in groups of five rats/cage (social rear-
ing) for five weeks. These rats were placed into a circular open field arena
following intraperitonean injection of either saline or L-NAME 30 min
before a 5 min test.
Results: Under high light condition, untreated isolation reared rats exhibited hypolocomotor activity (indicated by reduction of total zone transitions) and reared less than socially reared rats. Both socially and isolation
reared rats spent more time in the outer zone (P<0.05), however, isolation reared rats spent longer time in the inner zone than the social reared
rats. Systemic administration of L-NAME (10 and 25 mg/kg i.p.) decreased
locomotor activities (total zone transitions) in socially reared rats, in a
dose-related manner, but had no effect on the isolation reared rats.
L-NAME significantly reduced the number of reared and time spent on
the inner zone in both socially and isolation reared rats, however, these
effects were greater in the isolation reared rats.
Conclusion: The present results indicate that rearing rats in social isolation alter the open field behavior and increase the anxiolytic-like effect of
L-NAME in the mature rats. This abnormality may reflect alterations of
nitric oxide and other central neurotransmitters such as GABA, 5-HT and
NA in the central nervous system of isolation reared rats.
References: 1. Nikolaev, E., Kaczmarek, L., Zhu, S.W., Winblad, B.,
Mohammed, A.H. (2002) Brain Res. 957:91-98. 2. Wongwitdecha, N.,
Kasemsook, C., Plasen, S. (2006) Behav. Brain Res. 167: 232-236.
3. Wongwitdecha, N., and Thaidee, H. (2006) The International Journal of
Neuropsychopharmacology 9(Suppl 1): S208. 4.
Wongwitdecha, N.
and Marsden, C.A. (1996) Brain Res., 715, 119-124. 5.
Wongwitdecha, N. and Marsden, C.A. (1996) Behav. Brain Res., 75, 27-32.
P-28-09
Selective antiaggressive effect of partial alpha-2 agonist
naphtylmedetomidine in mice
Martin Votava
Charles University, 3rd Faculty of Medicine, Prague 10, Czech Republic
Ladislav Hess, Miloslav Krsiak
Introduction: The aim of the present study was to ascertain behavioral
profile of naphtylmedetomidine. Naphtylmedetomidine is a partial alpha2 adrenoreceptor agonist. Full alpha-2 adrenoreceptor agonists are clinically used e.g. to induce sedation in patients in the intensive are units.
Behavioural effects of partial alpha-2 adrenoreceptor agonists have been
little studied so far.
Method: Behavioral effects of naphtylmedetomidine were studied in the
activity cage and in the social conflict test in mice which provides a wide
spectrum of behavioural activities in two types of animals (aggressive and
sociable mice) and in the activity cage.
Results: Naphtylmedetomidine (150-1200 g/kg i.p.) dose-dependently
decreased locomotion in the activity cage, but the lower doses of the
drug did not reduce locomotion during social conflict. The significant
effect during social conflict was a selective and dose dependent antiaggressive effect in aggressive mice observed already after the lowest dose,
while the sociability and locomotion were attenuated only after the highest dose of naphtylmedetomidine. In the sociable mice, the reduction of
social investigation (sociability) was observed after the lowest dose,
while the locomotion was reduced after the higher doses of
naphtylmedetomidine.
Conclusion: Naphtylmedetomidine showed a very selective antiaggressive effect, observed already after the lowest dose used in the study. This
effect is more selective than that observed with dexmedetomidine, suggesting promising role of partial alpha-2 adrenoreceptor agonists in the
treatment of aggressive states.
References: Supported by the grants GACR 305/05/P003, GACR
305/06/0283 and the VZ MSMT 0021620816
P-28-10
Sertindole in Huntingtons disease: The first case report
Markus Magnet
Universityclinic Graz Austria, Psychiatry, Austria
Anna Hdl, Raphael Maria Bonelli, Hans Peter Kapfhammer
Introduction: HD is a neurodegenerative disorder which is autosomal
dominantly inherted. The genetic defect is located on the short arm of the
fourth chromosome and leads to an increased number of Cytosine
Adenine Guanine (CAG) base triplets. HD clinically shows a trias of symp-
toms. Hyperkinesia, psychiatric symptoms like depression and psychosis,

and ultimately dementia. It is wellknown and documented that neuroleptic drugs reduce hyperkinetic movement in HD.
Method: We describe the case of a 36 year old woman with genetically
proven HD. When she was referred to our department she showed severe
hyperkinetic movements which were evaluated with the UHDRS. Chorea
scored to 25 points which is severe. Sertindole 16 mg/d was given for a
one week periode. The effects of the treatment were evaluated by another
UHDRS after five days.
Results: . The score for chorea improved significantly to 3 points but only
due to highly increasing rigidity (parkinsonism from 6 to 9 points) which
worsened life-quality for our patient. She was no longer able to get out
of bed without assistance and activities of daily life such as cutting food
by herself were no longer possible. Choreatic hyperkinesias are commonly
treated with atypical neuroleptics. There are some reports on olanzapine,
quetiapine, clozapine and zotepine, but, to our knowledge, sertindole has
not been described before.
Conclusion: As an atypical neuroleptic drug sertindole has good antipsychotic effects and very few EPS-side-effects, but, as we could see in our
case, it can induce rigidity. This is only an anecdotal case report and further study is needed. Nevertheless the authors suggest that sertindole
should not be the treatment of choice for choreatic movement in HD.
P-28-11
Anxiolytic and panicolytic effects of escitalopram in the
elevated t-maze
Frederico Graeff
University of Sao Paulo, Psychiatry, Ribeirao Preto, Brazil
S. Pinheiro, C. Del-Ben, H. Zangrossi
Introduction: Escitalopram is a highly selective inhibitor of serotonin
reuptake that is used to treat anxiety disorders. In the present study, we
investigated the effects of escitalopram in the elevated T-maze (ETM), an
animal model of anxiety and panic.
Methods: The ETM has one arm enclosed by walls that is perpendicular
to two opposed open arms, all elevated from the floor. Inhibitory avoidance of the open arms, trained in the enclosed arm, has been related to
generalised anxiety disorder, while one-way escape from one open arm,
to panic disorder. After the ETM test, locomotion was measured in a
square arena. Rats were randomly allocated to five groups, respectively
administered with 15 mg/kg imipramine, 2, 4 and 8 mg/kg escitalopram
or saline, orally. Three regimens of drug administration were used: acute
(single), subchronic (once daily for 14 days) and chronic (21 days). ANOVA
statistics was used.
Results: After acute administration, the three doses of escitalopram
impaired avoidance (anxiolytic effect), while imipramine was ineffective.
Escape was unaffected by either drug. With subchronic administration,
both drugs were ineffective on either avoidance or escape. After chronic
treatment, avoidance was impaired by imipramine and by the two highest
doses of escitalopram. In addition, escape was impaired (panicolytic
effect) by imipramine and by the highest dose of escitalopram.
Locomotion measured in a square arena was increased by the three doses
of escitalopram, given chronically.
Conclusion: Both imipramine and escitalopram had anxiolytic and panicolytic effects in the ETM after chronic administration. Acutely, only escitalopram decreased anxiety. Since no such effect was observed following
subchronic administration, the mechanisms of the early and late anxiolytic actions of escitalopram are likely to be different. Chronic escitalopram
had a psychostimulant-like effect in the arena.
P-28-12
Ziprasidone in the treatment of borderline personality disorder: A double-blind, placebo-controlled study
Juan Carlos Pascual
Joaquim Soler, Thais Tiana, Judith Barrachina, Dolors Puigdemont,
Rosario Prez-Egea, Enrique Alvarez, Vctor Perez
Introduction: Ziprasidone is an atypical antipsychotic with a favorable
efficacy and safety profile due to its lower risk of inducing extrapyramidal
symptoms. Only one open-label, uncontrolled study have been published
199
on the use of ziprasidone to treat Borderline Personality Disorder (BPD)

patients attending the emergency psychiatric units for a crisis. Results
from this uncontrolled study appear to support its efficacy and safety for
treating acute BPD patients (1). The aim of this study was to determine
the efficacy and safety of ziprasidone versus placebo in the treatment of
adult patients with BPD.
Method: A total of 60 BPD patients were included in a single-center,
double-blind, placebo-controlled study. The subjects were randomly
assigned to ziprasidone or placebo in a 1:1 ratio following a two weeks
baseline period. The study duration was 14 weeks and all subjects
received psychotherapy. Measures included scales and self-reports related
to affective, behavioral, psychosis and general psychopathology
domains.This report presents data from clinical measures of safety and
treatment response.
Results: The sample consisted in mild-severe BPD patients (7.38 DIB-R)
with moderate affective and psychiatric sintomatology. At the baseline,
those clinical and sociodemographic variables are comparable and no statistically significance is observed between ziprasidone and placebo
samples. At the end of the study, the global retention rate after 3 months
of treatment was 48,3 %. Further analysis comparing both conditions of
treatment will be included in the poster.
Conclusion: This is the first double-blind, placebo-controlled study on
the effect of ziprasidone in BPD patients. Conclusions will be commented
in the poster.
References: 1 Pascual JC, Oller S, Soler J, et al. Ziprasidone in the acute
treatment of borderline personality disorder in psychiatric emergency
services. J Clin Psychiatry. 2004 Sep;65(9):1281-2.
P-28-13
Gender differences in consumption of benzodiazepines by
human population and in their effects on mice and rats
Viktor Goudochnikov
UNIJUI, DCSa, Ijui - RS, Brazil
Introduction: At present, only scarce literature data exist on gender differences in psychotropic drug consumption in some countries. Besides,
possible causes and consequences of such differences are not clear yet.
Method: In order to resolve partially a problem, we have evaluated consumption of benzodiazepines (BZD), according to prescription data of
controlled medications in commercial pharmacies. As a whole, a number
of pharmacies in many small towns were sampled during the years 2004
and 2005 in North-Western region of the state of Rio Grande do Sul (RS),
Brazil. Anxiolytic effects of alprazolam were evaluated in adult male and
female mice, using elevated plus maze test. Effects of diazepam (alone
and in combination with dexamethasone or methylprednisolone) on body
growth, organ weights and other indices were evaluated in male and
female rats of different age groups. Data were treated by means of
Student t, Mann-Whitney and exact Fisher tests.
Results: The results collected in human population have demonstrated
higher consumption of diazepam, bromazepam, alprazolam and
lorazepam, as well as feminine predominance in the consumption of the
majority of BZD. In general, our results confirmed literature data on gender differences in psychotropic drug use. Female mice have shown significantly higher response to anxiolytic action of alprazolam, as compared to
males. Several gender differences were observed also in the effects of
diazepam on various parameters in rats. For example, diazepam was able
to diminish some glucocorticoid effects only in female rats.
Conclusion: Since females consume more BZD, then, perhaps, they
should demonstrate higher and/or more specific responses to their pharmacologic action. Indeed, it may be the case, according to our data on
experimental models employed. In conclusion, both pharmacoepidemiological data on psychotropic drug consumption and drug surveillance
results in experimental models on laboratory animals are equally important, in order to justify and promote rational use of BZD and other psychotropic drugs, especially in women.
References: Kapczinski, F. et al. Use and misuse of benzodiazepines in
Brazil: a review. Substance Use & Misuse, v.36, p.1053-1069, 2001. Lima,
M.S. et al. Gender differences in the use of alcohol and psychotropics in
a Brazilian population. Substance Use & Misuse, v.38, p.51-65, 2003.
200
P-28-14
Using pattern and potential inappropriate use of benzodiazepines in Taiwan
Erin Chia-Hsuan Wu
Sun Yat-Sen Cancer Center, Department of Pschiatry, Taipei, Taiwan
I-Shou Chang, Fang-Yu Tsai, Kehming Lin
Introduction: Benzodiazepines(BZDs) are the most frequently prescribed
psychotropic drugs in Taiwan, but inappropriate prescribing is not uncommon. Therefore, the aims of the study were to investigate (1) the prevalence of BZD use; (2) the pattern of use, and (3) the potentially inappropriate prescriptions.
Method: We applied a computerized dataset named Longitudinal
National Health Insurance Database 2003 to investigate the utilization of
BZDs in 2003. The samples were representative of the insured, as well as
the general population in Taiwan. According to the WHO anatomical
therapeutic chemical classification system, we analyzed the prevalence of
BZDs use, the usage level, expressed in defined daily dose (DDD) per 1000
inhabitants per day, and the prescription patterns. We identified the
potential inappropriate use of BZDs in terms of the simultaneous use of
multiple BZDs and the users with large annual amount (>360DDD/personyear).
Results: The one-year prevalent rate of BZD use was 18.63% for the
whole sample and 41.8% in those 65 years and older. Female consumed
more BZDs than male in all of the age groups. The DDD per 1000 inhabitants per day was 35.74. The top three prescribers in terms of frequency
were internists (29.41%), psychiatrists (18.11%), and general practitioners (15.91%). Regarding to potential inappropriate use, though short-acting BZDs were prescribed more often than long-acting ones, 25.53% of
the elderly still took long-acting BZDs. 20.34% of the users were once
prescribed more than one BZD in a medical visit. In the visits with any BZD
prescription, 18.87% were with more than one BZD prescription, 2.35%
were written 3 BZDs or more. 5.11% of users consumed more than
360 DDD/person-year; and there were more female users than males.
People taking BZDs had higher medical utilization than the general population (26.4 v.s.14.3 medical visits per year)
Conclusion: BZDs use was prevalent and increasing in Taiwan. Female
and elderly were prone to use more BZDs. Though there still was no consensus on the operating criteria for potentially inappropriate use, according our definitions, it was not uncommon. This issue deserves further
exploration especially in regard to the associated sociodemographic and
clinical variables, as well as the users medical cost and health outcomes.
References: 1. Su TP, et al. Utilization of psychotropic drugs in Taiwan:
An overview of outpatient sector in 2000. Chin Med J 2002; 65: 378-391
P-29
Psychopharmacology/Antipsychotics II
P-29-01
Randomised, double-blind clinical trial of clonazepam versus carbamazepine as add-on to lithium in acute mania
Amresh Shrivastava
University of Western Ontario, London, Ontario, Canada
J. K. Trivedi, Nimesh G. Desai, K. Krishna Murthy, Ram Avatar Singh,
Rajul Tandon, Virendra Singh Yadav
Introduction: Several limitations in management of acute mania continue to confront clinicians, in spite of a range of new molecules being available. g. Rapid resolution of manic symptoms. Benzodiazepines have been
reported to be effective in tranquilising the manic state. Clonazepan represents unique benzodiazepines, which have been evaluated in mania,
and requires further investigation. The present mutlicentric, study has
been undertaken to evaluate efficacy and safety of clonazepam as an
additional pharmacological agent to Lithium carbonate as compared to
carbamezapine.
Method: In a multicentric study Randomized, Double-blind, Parallel

Group Trial was conducted using Lithium and Clonazepam verses Lithium
and Carbamazepine in a 33 weeks trial. Haloperidol for Excitability and
Promethazine for EPS was used whenever required only. Efficacy and outcome Evaluation was done Using BPRS, BMRS, CGI, and SADS-C. Side
effects were recorded using a checklist. Data was pooled and analysed.
The study was carried out in three centers in India
Results: In a comparable study groups it was observed that 52 patients
in Carbamazapine (CBZ) group and 53 in clonazepam group (CNP) completed the trial, The average duration of therapy in the carbamazepine
groups was 19.25 days as compared to 19.41 days in the clonazepam
group. The average dose of lithium per day in the carbamazepine and the
clonazepam group was 1184.83 (53.44) mg and 1193.14 (42.73) mg
respectively. he average dose of carbamazepine per day was 439.27
(150.05), and that of clonazepam was 2.70 (1.52) mg. on Total Brief
Psychiatric Rating Scale scores a reduction of 32.20% ( 13.85%) and
34.58% (16.40%) was found in the clonazepam and carbamazepine
group respectively. The difference was statistically non-significant in both
the intent-to-treat and in the completed-patients populations. In each
group there was a significant decrease in the total scores of median CGIS
scores, which declined from 4 (Moderately ill) to 3 (Mildly ill) and from 5
(Markedly ill) to 2 (Borderline mentally ill) in the carbamazepine and clonazepam group respectively. On total Beech Refuels Mania Rating Scale
(BRMS) scores, there was a 67.49% (26.57%) and 65.16% (27.29%)
decrease in the symptoms of acute mania in carbamazepine and clonazepam group respectively. On total SADS-C Mania Component scale
scores, there was a 67.23% (25.82%) and 64.62% (26.33%) decrease
across both the groups. Each group showed significant improvement,
however there was no significant difference in the extent of improvement
between the two groups on any measure. Less than 5% of the patients
had the any signs of depression or abnormal involuntary movements. 36
events in adverse event profile were noted in the carbamazepine group as
compared to 25 events in the clonazepam group. In none of the patients,
the dose of carbamazepine or clonazepam had to be reduced due to the
observed adverse events.
Conclusion: The present study highlights that efficacy and outcome are
favourable to clonazepam as on no parameter any statistically significant
difference was observed between clonazepam and carbamezapine group
when added to lithium carbonate. Clonazepam appears a promising molecule because of variety of mechanism of action to be effective in treating acute mania. Acknowledgement: The study was sponsored by
research grant from Nicholas-Piramal India limited
P-29-02
Effectiveness of quetiapine treatment in patients with
manic episode who didnt respond well to previous treatment
Oliver Kozumplik
Vrapce Psychiatric Hospital, University Department, Zagreb, Croatia
Suzana Uzun, Ninoslav Mimica, Vera Folnegovic-Smalc
Introduction: Bipolar disorder is a serious public health problem with significant morbidity and mortality, and typically recurrent with lifelong vulnerability. Previous investigations showed that quetiapine has efficacy
against manic symptoms in patients with bipolar I disorder. Objective: to
assess the effectiveness of quetiapine treatment in the open-label, noncomparative, 12-week study with flexible doses of quetiapine in patients
with manic episode who had inadequate response to or intolerance of
their previous therapy.
Method: Thirty patients with manic episode according to DSM-IV TR
diagnostic criteria were switched to quetiapine during hospitalization in
Vrapce Psychiatric Hospital in the period from April to July 2006. Patients
were switched due to inadequate response to or intolerance of their previous therapy. The Clinical Global Impression (CGI) and Young Mania
Rating Scale (YMRS) were used in order to assess effectiveness of treatment with quetiapine. Quetiapine was introduced at dose of 50 mg on
day one, followed by 100 mg, 200 mg and 300 mg on days 2, 3, and 4.
After day 4, the daily dosage was between 300 mg and 900 mg. The
patients were assessed prior to initiation of quetiapine treatment, on
weekly basis during first four weeks and later every four weeks of continuous therapy with quetiapine. Statistical significance was set to p<0.05.
Results: After twelve weeks of continuous therapy with quetiapine,

YMRS total score significantly decreased in the group of patients who
were switched to quetiapine because of inadequate response to previous
therapy, but not in the group of patients with intolerance of their previous therapy. The mean CGI severity score for all patients improved from
3.9 (moderately ill) to 2.4 (mildly ill).
Conclusion: Administration of quetiapine was clinically beneficial for the
patients with manic episode who had inadequate response to or intolerance of their previous antipsychotic therapy.
References: 1. Jarema M. Atypical antipsychotics in the treatment of
mood disorders. Curr Opin Psychiatry 2007;20(1):23-29. 2.
GUY W
1976 Clinical global impressions. In: ECDEU Assessment Manual for
Psychopharmacology Revised, US Department of Health, Education and
Welfare, Rockville, Maryland, p 217. 3. Young RC, Biggs JT, Ziegler VE,
Meyer DA. A rating scale for mania: reliability, validity and sensitivity. Br J
Psychiatry 1978;133:429-435. 4. Kozumplik O, Folnegovic-Smalc V, Jukic
V, Mimica N, Uzun S. Quality of life in patients with paranoid schizophrenia treated with typical and atypical antipsychotics. Sch Research
2004;67(1):228.
P-29-03
Amisulpride versus risperidone treatment for behavioral
and psychological symptoms in patients with dementia of
the Alzheimers type: A randomized, open prospective
study
Paik In-Ho
Kangnam St. Marys Hosp, Psychiatry, Seoul, Republic of Korea
Seung-Kyu Bang, Hyun-Kook Lim, Chul Lee, Chang-Uk Lee
Introduction: The aim of this study was to evaluate the effectiveness and
tolerability of both amisulpride and risperidone for treating the behavioral
and psychological symptoms of dementia (BPSD) in patients with dementia
of the Alzheimers type (DAT).
Method: Twenty-eight patients with DAT were randomly assigned to
treatment with either amisulpride or risperidone for 8 weeks. The effectiveness of the treatments was assessed with the Neuropsychiatry
Inventory (NPI) and the Clinical Global Impression-Severity of Illness (CGI-S)
scale. The Simpson-Angus Rating Scale, the Barnes Akathisia Rating Scale
and the Abnormal Involuntary Movement Scale were used for the assessment of side effects.
Results: The NPI and CGI-S scores were significantly decreased over time
in both treatment groups without any significant group difference and
time by the group interaction effect (F=71.85, P<0.0001). There were no
serious adverse events in both groups.
Conclusion: This study showed that either amisulpride or risperidone
would be effective and tolerable for treating patients with DAT.
Adequately powered studies with a head-to-head comparison design will
be mandatory to draw any definite conclusion.
References: Kindermann SS, Dolder CR, Bailey A, Katz IR, Jeste DV, et al.
(2002). Pharmacological treatment of psychosis and agitation in elderly
patients with dementia: four decades of experience. Drugs Aging 19:257276. McKeage K, Plosker, GL (2004 ). Amisulpride A Review of its Use in
the Management of Schizophrenia. CNS Drugs 18: 933-956.
P-29-04
Involvement of adenosinergic receptor system in an animal model of tardive dyskinesia and associated behavioural, biochemical and neurochemical changes
Shrinivas Kulkarni
University Institute of, Pharmaceutical Sciences, Chandigarh, India
M. Bishnoi, K. Chopra
Introduction: Tardive dyskinesia is a syndrome characterized by repetitive involuntary movements usually involving mouth, face and tongue. It is
considered as the late onset adverse effect of prolonged administration of
typical neuroleptic drugs. Adenosine is now widely accepted as the major
inhibitory neuromodulators in the central nervous system besides GABA.
Both, agonists of adenosine A1 and A2 receptors and the antagonists of
A2A receptors are known to protect against neuronal damage caused by
toxins as well as they can also protect against the cell damage inflicted by
reactive oxygen species.
201
Methods: The present study investigated the effect of adenosine and

A2A receptor antagonist, caffeine in an animal model of tardive dyskinesia by using different behavioural (orofacial dyskinetic movements, stereotypic rearing, locomotor activity, % retention), biochemical (lipid peroxidation, reduced glutathione levels, antioxidant enzyme levels (superoxide
dismutase and catalase) and neurochemical (neurotransmitter levels)
parameters.
Results: Chronic administration of haloperidol (1 mg/kg i.p. for 21 days)
significantly increased vacuous chewing movements (VCMs), tongue protrusions, facial jerking in rats which was dose dependently inhibited by
adenosine and caffeine. Chronic administration of haloperidol also resulted in an increased dopamine receptor sensitivity as evident by increased
locomotor activity and stereotypic rearing after day 14. Chronic administration of haloperidol also decreased % retention time on elevated plus
maze paradigm. Treatment with adenosine or caffeine reversed these
behavioural changes. Besides, haloperidol also induced oxidative damage
in all regions of brain which was prevented by caffeine and adenosine,
especially in striatum. On chronic administration of haloperidol there was
a decrease in dopamine and norepinephrine turnover which was dosedependently reversed by treatment with adenosine or caffeine. When caffeine and adenosine were co-administered, there was no synergistic
effect, possibly due to mutual antagonistic effects.
Conclusion: The findings of the present study suggested the involvement
of adenosinergic receptor system in the genesis of neuroleptic- induced
tardive dyskinesia.
P-29-05
The opposite effect of a low and a high dose of serotonin1A agonist on deficit in sensorimotor gating induced by
NMDA antagonist
Vera Bubenikova-Valesova
Jiri Horacek, Martin Votava, Tomas Palenicek
Introduction: Several antipsychotic drugs have partial agonistic actions
on serotonin 5-HT1A receptors, and it is believed that a 5-HT1A receptor
agonist might improve the negative symptoms and cognitive function
deficits in schizophrenia [1]. We investigated the effect of different dose
of 5-HT1A agonist on deficit in information processing in animal model
of schizophrenia-like behavior (induced by administration of NMDA
antagonist; MK-801).
Method: Male Wistar rats received two doses (0.025 and 1 mg/kg) of
5-HT1A receptor agonist 8-OH-DPAT and/or MK-801 in two different
doses, 0.1 mg/kg or 0.3 mg/kg. We measured sensorimotor gating by
testing prepulse inhibition of acoustic startle response (PPI).Data was
evaluated bt two-ways ANOVA with 8-OH-DPAT treatment as one factor
and MK-801 treatment as the second factor. Comparisons between treatment groups were conducted using the Student-Newman-Keuls Method
post-hoc test.
Results: We found an opposite effect of the low and high 5-HT1A receptor agonist dose on MK-801 induced deficit in PPI. The low dose of 8-OHDPAT, which preferentially acts on presynaptic 5-HT1A receptors, restored
the deficit in PPI in MK-801 (0.1 mg/kg) treated rats. However, the high
dose of 8-OH-DPAT, which activates both pre- and postsynaptic 5-HT1A
receptors, decreased PPI after administration of MK-801.
Conclusion: Based on our results we suggest that the low dose of 8-OHDPAT, which activates predominantly presynaptic 5-HT1A receptors [2]
with subsequent decrease of serotonin release in synaptic terminals, has
an antipsychotic-like profile in our model of schizophrenia-like behavior.
These results are interesting in relation to its possible utilization to restore
deficits in information processing in patients with schizophrenia.This
research was supported by grant GACR 305/06/0283, MEYS 1M0517
and MHCR MZ0PCP2005 .
References: [1] Roth BL, Hanizavareh SM, Blum AE (2004),
Psychopharmacology 174: 17-24. [2] Yocca FD, Iben L, Meller E (1992),
Mol Pharmacol 41:1066-1072.
202
P-29-06
Long-term antipsychotic monotherapy: Clinical outcomes
from the 3-year Intercontinental Schizophrenia Outpatients
Health Outcomes Study (IC-SOHO)
J. Rovner
Eli Lilly, Interamerica, Capital Federal, Argentina
H. I. Silva, J. Zarra, S. Zamora, S. Battaglia, T. West, Amanda Lowry,
M. Dossenbach
Introduction: Schizophrenia commonly follows a remitting course requiring life-long management. The observational design of IC-SOHO allows
us to explore treatment strategies and outcomes in a diverse real-life
population over a 3-year period. Here we describe the comparative effectiveness of antipsychotic monotherapies.
Method: Clinical and functional assessment of outpatients initiating or
switching to olanzapine (olz, n=2641), risperidone (ris, n=863), quetiapine (quet, n=142) and haloperidol (hal, n=189) monotherapy for schizophrenia was made at 0, 3, 6, 12, 18, 24, 30, and 36 months. KaplanMeier estimates of time to discontinuation, response, relapse, and remission were calculated while patients remained on their baseline (B)
monotherapy. Response=Clinical Global Impressions (CGI) total score
decreased by >2 points lower than B, if the B CGI total score was =4, or
>1 point lower if the B CGI total score =3. Remission=CGI total, positive,
negative, and cognition scores =2 for 2 consecutive visits > 6 months post
baseline and no inpatient admissions.
Results: Patients on olanzapine were more likely (p<.001) to maintain
their monotherapy than patients on risperidone, quetiapine, or haloperidol; and were also more likely (p<.001) to respond than risperidone, quetiapine or haloperidol patients, with median response times (months) of:
olz 5, ris 6, quet 11, and hal 12. Median times to remission (months) were
- olz 25, ris 36, and quet 36; patients on olz were more likely (p<.001) to
experience remission than ris or hal patients. For haloperidol, the risk of
relapse was 2.8 times that (p<.001) of olanzapine, and 2.1 times that
(p=.006) of risperidone.
Conclusion: Antipsychotic monotherapy is a viable treatment strategy for
schizophrenia, however there appears to be variable effectiveness across
compounds.
P-29-07
Case report: Late respiratory dyskinesia, an unusual
adverse effect
Erika Quintanilla
Universidad de Chile, Residente de Psquiatria, Santiago, Chile
Maritza Castiglioni
Introduction: An older woman who has schizophrenia was diagnosed
with late respiratory dyskinesia (LRD). Before this diagnosis was made, this
patient was considered to have a chronic respiratory insufficiency during
at least 5 years, but with no a clear illness that explain that condition. LRD
is a very rare adverse effect that occurs usually in older people exposed to
classic antipsychotics for a long time, which usually have other types of
dyskinesia. Here we exposed a bibliographic review of this uncommon
complication of antipsychotics.
Method: The medical history of the patient with LRD was analyzed and
compared with the information found in the bibliographic review.
Results: There are scarce publications about LRD. In a few reports is
described a prevalence of 1.2 to 2.3% between patients who use chronically classics antipsychotics. Because of the lack of suspicion of this illness, it is infrequently reported. In most cases patients are considered to
have a malfunction of the respiratory system but with a no anatomical
substrate, receiving inappropiate treatments.
Conclusion: Symptoms associated with the respiratory system among
chronic users of classical antipsychotics make necessary the differential
diagnosis between respiratory syndromes and LRD. It is very important the
suspicion and the earlier diagnosis of LRD to offer an effective treatment
to a serious adverse effect.
P-29-08
Aripiprazole in treatment of schizophrenia with comorbid
heroin dependence
Vyacheslav Sushko
Odessa State Medical Univ., Chair of Psychiatry, Ukraine
Introduction: Comorbid heroin abuse adversely affects clinical outcomes
in schizophrenia. The debilitation of schizophrenia worsens markedly with
comorbid heroin dependence. To date, no medications have conclusively
demonstrated effects against both schizophrenia and comorbid heroin
dependence simultaneously. People with schizophrenia and comorbid
heroin abuse may require considerable support from health care professionals, in most cases over a long period. The aims of this study were to
assess the efficacy, safety, and tolerability of aripiprazole, 30 mg, for alleviate heroin craving in patients with schizophrenia and comorbid heroin
dependence. Secondary objectives were to assess heroin craving longitudinally in comorbid schizophrenia patients and to describe its time course
by means of the Heroin Craving Questionnaire (HCQ).
Method: Twenty-three heroin-dependent males with comorbid schizophrenia who met IDC-10 criterias for schizophrenia and heroin dependence were seeking treatment. Patients remained hospitalized for at least
4 of the weeks. They were interviewed by psychiatrists and tested using
Heroin Craving Questionnaire, Brief Psychiatric Rating Scale, Positive and
Negative Syndrome Scale (PANSS) scores in the beginning and at the end
of treatment. Each received aripiprazole as their sole neuroleptic agent at
a maximum dose of 30 mg once daily. Maintenance doses were individual for each patient according to their response to treatment after a
satisfactory stabilization.
Results: The results suggest that aripiprazole is well tolerate in schizophrenia and comorbid heroin-dependent individuals and may reduce
heroin-related withdrawal symptoms and schizophrenia symptoms simultaneously. Mean heroin craving scores declined significantly (P = 0.028).
Declining psychosis scores were associated with declining heroin craving
(r = 0.84, P < 0.01). Patients with schizophrenia treated with aripiprazole
have reduced heroin craving.
Conclusion: Aripiprazole, may provide new avenues for pharmacological
treatment of heroin dependence in comorbid schizophrenia subjects.
Aripiprazole is effective, safe, and well tolerated for the positive and negative symptoms in schizophrenia and heroin-related withdrawal symptoms. Aripiprazole, 15 mg once daily, is an effective, well-tolerated treatment for prevention of relapse in patients with chronic, stable schizophrenia and comorbid heroin dependence. Aripiprazole represents a promising new option for the long-term treatment of schizophrenia and comorbid heroin dependence. Aripiprazole may further decrease the potential
for abuse, especially among heroin-dependent injection-drug users.
P-29-09
Antimanic efficacy of amisulpiride
Lorenzo Livianos-Aldana
Hospital Universitario La FE, Psiquiatria, Valencia, Spain
Sergio Arques Egea, Javier Castello Gasco, Pilar Sierra SanMiguel, Teresa
Rubio Granero, Alejandro Povo Canut, Luis Rojo Moreno
Introduction: The clinical experience acquired in every day practice at
our Bipolar Disorder Unity, show us that the second generation antipsychotic Amisulpride has an important antimanic action. The aim of this
study is to test this clinical impression.
Method: The retrospective analysis was performed on the clinical records
of 54 patients from our Bipolar Disorder Unity. The measures include the
rating from the Chinese Polarity Inventory (CPI) and Numeric Evaluation
Scale (NES) questionnaires and the clinical evaluations. Whenever possible, each patient was compared with himself at different manic episodes
(treatment with Amisulpride or other antipsychotics). The statistical analysis were performed with the SSPS v12.0
Results: Patients who received Amisulpride for the manic episode shown
faster normalisation of the CPI and NES questionnaires scores than
patients who received other antipsychotic. We observed a faster clinical
improvement of the Amisulpride treatments group than the other
antipsychotic group.
Conclusion: The antipsychotic Amisulpiride seems to have an antimanic

effect superior to those of other antipsychotics. Double-bind clinical trials are needed to test it.
References: Carta MG, Zairo F, Mellino G, Hardoy MC, Vieta E. An open
label follow-up study on amisulpride in the add-on treatment of bipolar I
patients. Clin Pract Epidemol Ment Health. 2006 Aug 24;2:19. Vieta E,
Ros S, Goikolea JM, Benabarre A, Popova E, Comes M, Capapey J,
Sanchez-Moreno J. An open-label study of amisulpride in the treatment
of mania. J Clin Psychiatry. 2005 May;66(5):575-8.
P-29-10
Amisulpride in the treatment of depression with psychotic,
melancholic and catatonic features
Maria Ladea
Clinical Hospital, Prof. Dr. Al. Obregia, Bucharest, Romania
Mihaela Ruxandra Dumitrescu
Introduction: Amisulpride is a unique atypical antipsychotic which at low
doses, selectively blocks D2/D3 dopamine receptors presynaptically in the
frontal cortex, possibly enhancing dopaminergic transmission. The
dopamine deficit in cortical prefrontal areas can explain both some symptoms of depression and negative symptoms of schizophrenia. In the present study we investigated the effects of amisulpride in depression with
psychotic, melancholic and catatonic features and especially its efficacy in
psychomotor retardation.
Method: In an open-label, non-blinded study, 17 patients with DSM-IV
major depressive disorder (MDD) with psychotic features, melancholic
features and catatonic features were treated with amisulpride and an
antidepressant for 6 weeks. All patients were evaluated regarding their
clinical improvement using the Hamilton Rating Scale for Depression
(HAM-D-17 items), and Positive and Negative Syndrome Scale (PANSS).
Secondary efficacy measures included scores on the Clinical Global
Impressions-Improvement (CGI-I) and -Severity (CGI-S) scales. Clinical
response was defined as a 50% or greater decrease in depressive symptoms during the course of the trial (baseline to endpoint), as measured by
the HAM-D-17 total score. Decrease in PANSS score was also registered
at the end of the period.
Results: Fourteen of 17 patients completed the trial. All 14 completers
achieved remission 6 weeks after the initiation of the treatment (HAM-D
score = 7). Common adverse effects were mild akathisia and nausea.
Conclusion: These results indicate that the combination of amisulpride
with antidepressants is a good therapeutic option in obtaining a rapid
amelioration of severe depression with marked psychomotor retardation.
Based on this clinical signal, randomized controlled trials are necessary to
evaluate this role of amisulpride.
References: 1. Montgomery SA: Dopaminergic deficit and the role of
amisulpride in the treatment of mood disorders. Imperial College,
University of London, UK. Int Clin Psychopharmacol. 2002 Dec;17 Suppl
4:S9-15. . Quintin P, Thomas P: Efficacy of atypical antipsychotics in
depressive syndromes. Encephale. 2004, Nov-Dec, 30(6):583-9.
P-29-11
Age-related susceptibility to chronic haloperidol-induced
orofacial dyskinesia: Biochemical and neurochemical
evidence
Mahendra Bishnoi
Panjab University, Cpebs, Chandigarh, India
S. K. Kulkarni, K. Chopra
Introduction: Aging is a continuous and intrinsic process of systems
deterioration with time. Although mean prevalence of tardive dyskinesia
(TD), a neurological disorder associated with chronic haloperidol administration is 20-25 % but cumulative rates of this disorder increases significantly in patients aged 55 or more.
Methods: The present study investigated the effect of aging on spontaneous development of orofacial dyskinesia and tried to find out the interactive substrate which is activated by chronic neuroleptic treatment and
result into premature emergence of tardive dyskinesia in adult animals.
Various behavioural (orofacial dyskinetic movements, stereotypy, locomotor activity, % retention), biochemical (lipid peroxidation, reduced glutathione levels, antioxidant enzyme levels (SOD and catalase) and neurochemical (neurotransmitter levels) parameters were assessed in young
(60-80 g), mature adult(180-200 g) and aged (380-400 g) rats.
203
Results: Aging resulted in significant increase in hyperkinetic motor activities, vacuous chewing movements (VCMs), tongue protrusions, facial
jerking and development of dopamine supersensitivity (increased locomotor activity and stereotypy) associated with oxidative damage in all regions of brain. The extracellular dopamine levels were also significantly
decreased (45 %) in forebrain of aged animals. Chronic administration of
haloperidol to aged animals further significantly increased all the parameters as compared to age matched control animals. Chronic administration
of haloperidol to matured adult animals showed similar changes especially hyperkinetic movements and oxidative damage in different parts of
brain. There was no significant change in young animals on chronic administration of haloperidol.
Conclusion: The findings of the present study suggested that free radical generation and development of dopamine supersensitivity are the
prime interactive substrates which are activated by chronic neuroleptic
treatment in matured animals and causing the development of tardive
dyskinesia where as these paradigms are increased with aging and result
into spontaneous orofacial hyperkinetic movements.
P-29-12
Assessment of a risk of venous thromboembolism and its
possible prevention in psychiatric patients
R. Maly
University Hospital, Psychiatry, Hradec Kralove, Czech Republic
J. Masopust, L. Hosak, K. Konupcikova
Introduction: Venous thromboembolism (VTE) is a multifactorial disease
which belongs to the main causes of morbidity and mortality in hospitalized non-surgical patients. The risk of a pathological blood coagulation
in psychiatric patients, especially those hospitalized and treated with antipsychotics, is important particularly in the first months of the treatment.
Methods: Based on the literary evidence on effective VTE prevention in
non-psychiatric patients, and our knowledge of specific VTE risk factors in
psychiatric patients (physical restraint, catatonia, hypohydration, obesity,
antipsychotic treatment), we constructed the algorithm of VTE prevention applicable exclusively in psychiatry.
Results: We suggest a five-step algorithm of prevention of venous thromboembolism in mentally ill people. Based on the magnitude of risk of
venous thromboembolism, we recommend regime (physical exercises),
mechanic (compressive tights), metabolic (hydratation) or pharmacological (low molecular weight heparin, unfractionated heparin) measures.
Conclusion: According to our knowledge, this is the first attempt to
design specific guidelines for thromboprophylaxis in psychiatry. We assume the suggested prevention to be safe, cheap, and effective.
P-29-13
Efficacy of quetiapin and combination of flufenazin and
one SSRI (paroxetin or sertralin) in treatment of PTSD
patients with psychotic symptoms
Vladimir Grosic
PB, Zagreb, Croatia
Anamarija Bogovi, Mate Mihanovi, Vera Folnegovsmalc, Petra Folnegovi
Grosi
Introduction: Aim of this paper is to evaluate efficacy of treatment of
examined patients treated with quetiapin as monotherapy and patients
treated with both flufenazin and one of SSRIs (paroxetin or sertralin).
Method: The patients have been diagnosed by criteria of DSM-IV classification. PANSS has been used to evaluate psychotic symptoms. Risk of
suicide has been evaluated too. Efficacy has been evaluated by PANSS and
CGI-I and CGI-S scales. Evaluation is conducted at the beginning of the
study and after that each two weeks during the 6 months period.In addition to the efficacy estimation, safety, tolerability and compliance have
been also estimated.
204
Results: Final results will be summerized at the end of March, 2007,

when the study will be completed.
Conclusion: The safety and tolerability profile of quetiapin monotherapi
is better then in combination therapy. Effective dose range in the majority of patients of 400 to 800 mg/day. Quetiapin is effective, fast acting
and well tolerated for the treatment of PTSD with psychotic simptoms.
References: 1. Naber D (1995) A self-rating to measure subjective effects
of neuroleptic drugs, relationship to objective psychopathology, quality of
life, compliance and other clinical variables. 2. Breznik D. Demografija:
Analiza, metodi i modeli. Beograd: Naucna knjiga, 1980 3. Bedenic B,
Kesic B., Korbar M, et al. Differential rates of psychoses in Croatia. Final
Report PL 480 02-276-2. Zagreb: Andrija tampar School of Public Health,
Medical faculty University of Zagreb, 1972. 4. DSM-IV, Naklada Slap,
Jastrebarsko, 1996.
P-29-14
Effects of clozapine in inmunological system. A clinical
study in schizophrenic patients
Alejandra Armijo
Santiago, Chile
Hernan Silva, Miguel Prieto, Alberto Bienna
Introduction: Clozapine is associated to inmunological adverse effects,
specially agranulocytosis in 0,8% of patients, potentially lethal, reason
why it requires strict hematological control. The mechanism is not completely elucidated. Althoughthe frequency of agranulocytosis has been
widely explored, there are not studies showing clinical inmunological
effects (recurrent infections) in schizophrenic patients in treatment with
clozapine, even being the hematological parameters within normal limits.
Objetives: to determine the frequency of pathologies secondary to
inmunological alterations in schizophrenic patients in treatment with
clozapine.
Method: A sample of 400 schizophrenic patients in treatment with clozapine controled in the Ambulatory Program of Atypical Antipsychotics.
Results: In process
Conclusion: In process
References: Multiples studies of clozapine and inmunological system.
OTHER - Poster
P-10
Other
T12 Other
P-10-01
Comorbidity between mood and substance dependence
disorders: Behavioral and neurochemical phenotyping in
laboratory rats
Francesco Leri
University of Guelph, Psychology, Canada
Craig Allen, Martin Sticht, Shabdis Djazayeri
Introduction: These experiments were designed to test the self-medication hypothesis of comorbid mood disorders and substance dependence, and to explore the involvement of the mesocorticolimbic dopamine
system in linking these disorders.
Method: Using the forced-swim test, 27 male Sprague-Dawley rats were
assessed for their individual predisposition to actively struggle to escape
from a cylinder filled with water. Five days following this test, rats underwent two consecutive tests of locomotion; the first following a saline
injection, and the second following a 15 mg/kg cocaine (IP) injection.
Three days following this test, the hot-plate test was used to assess their
analgesic threshold. All rats were then implanted with intravenous
catheters and, following recovery from surgery, tested in operant chambers for responding to: 1) a novel audio-visual cue; 2) the same cue after
its association with intravenous infusions of cocaine (150 in total,
0.05 mg/kg/inf); and 3) the same cue after a priming injection of cocaine
(15 mg/kg, IP) and after exposure to foot-shock stress. Following these
behavioral tests, the animals were sacrificed and the expression of mRNA
for the D1, D2 and D3 receptors, as well as for the dopamine transporter,
was measured within the ventral tegmental area, the dorsal and ventral
striatum, the amygdala, and the frontal cortex.
Results: Our behavioral data are partially consistent with the predictions
of the self-medication hypothesis of comorbidity. In fact, those rats
showing the least amount of struggling in the forced-swim test (i.e.,
depressive-like behavior; p<0.001), showed the highest responding for
novel stimulation (p<0.001), as well as the highest level of spontaneous
and precipitated cocaine-seeking behavior (p<0.05). Performance on the
forced-swim test, however, was not predictive of exploratory behavior,
sensitivity to the stimulatory action of cocaine, or analgesic threshold.
The data from the neurochemical essays will be available in March of
2007.
Conclusion: It is therefore possible to demonstrate the existence of a particular group of individuals predisposed both to behavioral depression and
to novelty- and drug-seeking behaviors using out-bred laboratory rats.
An understanding of the specific neurobiological profile of this group is
necessary to identify specific pharmacological interventions to effectively
manage substance abuse and relapse in individuals suffering from comorbid mood disorders.
P-10-02
Disorders of attention in dual diagnosis patients
Maciej Matuszczyk
Department of Psychiatry, Katowice, Poland
Krzysztof Krysta, Irena Krupka-Matuszczyk, Adam Klasik, Jacek Przybylo,
Zdzislawa Pilarz
Introduction: Most patients suffering from this disorder achieve worse
results in neuropsychological tests measuring attention than healthy controls. These results are also worse in comparison with patients suffering
from affective disorders. According to the literature these deficits remain
relatively stable over the course of the disease, however they may periodically increase and decrease according to the current clinical state. The
studies show that among the patients suffering from schizophrenia,
about 50% abused psychoactive substances during their lives. The data
concerning the impact of substance abuse on attention in schizophrenia
are inconsistent.
Method: The objective of this study was to examine continuous attention

differences between subjects with and without a dual diagnosis. A group
of 80 patients with schizophrenia were examined. 40 of them never used
illicit drugs, the other 40 also received a diagnose of addiction to psychoactive substances. The group with a comorbid addiction was examined after 6 weeks of detoxification and treatment in a therapeutic community. Continuous Performance Test was applied to for the neuropsychological assessment. The CPT-IP version of this test was used. The
patients were presented 450 stimuli in three groups.
Results: No statistically significant differences were found between two
groups when they had to omit the identical pair stimuli (finger-up). The
same happened in case of false alarms stimuli. However statistical significance appeared when the patients had to react to random stimuli. This
part of the test was performed better by the group of schizophrenic
patients without addiction.
Conclusion: The above inconsistence of the results may be due to the
complexity of attention deficits. It is possible that the impacts of psychoactive substances may be different on the mechanism responsible for
reaction to the sequence of experimentally important stimuli than to for
ignoring those stimuli, which originally were defined as unimportant.
References: 1. Pencer A., Addington J., 2003 Substance use and cognition in early psychosis. J Psychiatry Neurosci. 28, 48-54. Serper M.R.,
Bergman A., Copersino M.L., Chou J.C., Richarme D., Cancro R., 2000
Learning and memory impairment in cocaine-dependent and comorbid
schizophrenic patients. Psychiatry Res. 14, 21-32.Serper M.R., Copersino
M.L., Richarme D., Vadhan N., Cancro R., 2000 Neurocognitive functioning in recently abstinent, cocaine-abusing schizophrenic patients. J Subst
Abuse. 11, 205-213.
P-10-03
The role of serotonin 5-HT2A/C receptors in the behavioral
action of the synthetic drug 2C-B
Tomas Palenieek
V. Valesova-Bubenikova, J. Hora
Introduction: 2C-B (4-bromo-2,5-dimethoxyphenethylamine) is a psychedelic drug with an abuse potential. Whether it is used recreationally by
humans, almost no data about it?s pharmacology are available to date.
We have concentrated on the role of serotonin 5-HT2A/C receptors in
the behavioral action of 2C-B in two distinct behavioral testing procedures in rats - on the deficits in sensorimotor gating and on induced
changes in the locomotor activity.
Method: All experiments were carried out on male Wistar rats
(200-250g). In behavioral experiments each animal was tested only once.
Sensorimotor gating was tested in the test of Prepulse inhibition of
acoustic startle reaction (PPI)(SR-LAB, San Diego Instruments, USA) and
the locomotor activity in the open field test (Ethovision Color Pro. V3.1.1,
Noldus, NL). Animals were injected single subcutaneous dose (10, 25 or
50 mg/kg) of 2C-B hydrochloride salt 15 minutes before testing.
Antagonists of serotonin 5-HT2A/C receptors MDL-100907 (0.5 mg/kg),
SB-242084 (1.0 mg/kg) and ritanserin (2.5 mg/kg) or vehicle were injected s.c. 15 min and 60 min prior testing. For statistical analyses Analysis of
variance (ANOVA) was used (SigmaStat v.3.0) with p<0.05 considered as
significant.
Results: 2C-B significantly disrupted acoustic startle as well as PPI and
inhibited locomotion of animals in the open field. None of the three
antagonists restored the startle reaction; however selective antagonist at
serotonin 5-HT2A receptors MDL-100907 and mixed antagonist at serotonin 5-TH2A/C receptors ritanserin prevented the deficits in PPI while
selective serotonin 5-HT2C receptor antagonist SB-242084 had no effect
on PPI. In locomotor experiments MDL-100907 and ritanserin slightly
potentiated the hypolocomotor effect of 2C-B, on the contrary administration of SB-242084 antagonized the effects of 2C-B and had even produced hyperlocomotion.
Conclusion: Our results indicate that 2C-B influences both subtypes of
serotonin 5-HT2 receptors. While the disruption of PPI is associated predominantly with the 5-HT2A stimulation, the locomotor effects of 2C-B
are mediated via action at 5-HT2C receptors. The effect on acoustic startle
is suspiciously mediated by different serotonin receptors. This work has
been supported by the grant IGA MHCR NR-8785-3.
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OTHER - Poster
P-10-04
Mental and behavior disorders caused by the psychoactive
substance consumption as psychopatologies most found in
an psychiatric urgency and emergency service
Universidade Federal, do Rio Grande do Norte, Natal, Brazil
Introduction: The objective of this work is to analyze the prevalence of
the psychopathologies diagnosed in the patients assisted at the psychiatric urgency and emergency service of the psychiatric hospital Dr. Joo
Machado, located in Natal-RN - Brazil.
Method: Prospective work, according to International Classification of
Disease ICD, with protocol application to 80 patients assisted in the psychiatric urgency and emergency service at the hospital Dr. Joo Machado,
between the months of November and December of 2004.
Results: F00-F09 Organic Mental Disorder, besides the symptomatic ones
(6.25%); F10-F19 Mental and Behavior Disorders caused by the
Psychoactive Substance Consumption (33.75%), of the which F10.2
Mental and Behavior Disorders caused by the Alcohol Consumption Dependence Syndrome (22.22%) was the most found; F20-F29
Schizophrenia, Schizotypal and Delirious Disorders (26.25%); F30-F39
Humor and Affective Disorder (15%), being F31.2 Bipolar Affective
Disorder, Maniac Current Episode with Psychotic Symptoms (33.33%) the
most prevalent; F40-F48 Neurotic Disorders, Disorders Related with Stress
(6.25%), with 60% for F41.2 Anxious and Depressive Mixed Disorder.
More than one diagnosis (11.25%), in that 66.67% were related F10
Mental and Behavior Disorders caused by the Alcohol Consumption. And
patients without diagnosis - 20%.
Conclusion: A larger prevalence of patients could be observed with diagnosis of Mental and Behavior Disorders caused by the Psychoactive
Substance Consumption, being followed by Schizophrenia, Schizotypal
and Delirious Disorders, and Humor and Affective Disorder, being, therefore, the most found in this study. It is still valid to point out the important percentile value of patient with more than one diagnosis and the
important amount of patients without diagnosis.
P-10-05
Sweet related visual cue reactivity fades out until adulthood
Daniele Fabio Zullino
University Hospitals of Geneva, Division of Substance Abuse, Geneva,
Switzerland
Emmanuelle Fresard, Riaz Khan, Djamel Benguettat, Fabian Clays, Yves
Montagrin, Farfalla Ribordy, Sophie Taparel, Sonia Krenz, Yasser Khazaal
Introduction: Psychological and physiological responses associated with
craving has been shown in experimental studies to be elicited by cue
exposure to addiction related stimuli, but also to natural rewards. Skin
conductance activity is a sensitive measure of autonomic nervous system
activity that correlates well with other physiologic measures and the subject arousal associated with craving. This is due to ability of skin conductance to abruptly rise and fall in response to stimuli (within two seconds
delayed peaking in five seconds after presentation of stimulus) and to
delayed habituation of skin conductance response to arousal. The objective of the present study was to explore possible factors modulating the
cue related psychophysiological reactivity in response to images of
sweets.
Method: 166 volunteers (12 children [age < 12], 48 adolescents [age 1217], 99 adults [age 18-64], and 7 elderly subjects [age >64]) recruited during a scientific exposition for the general public, participated in a
3-minute laboratory session, during which they were submitted first to a
60-second presentation of neutral pictures (landscapes), which was followed by a 120-sec presentation of slides depicting different types of
sweets (i.e. chocolate, soft-ice, cookies etc). Skin conductance data was
collected via a ProComp+/Biograph system (Thought Technology).
Repeated measures GLM were computed. Initial cue reactivity (last 30 sec
of the neutral phase vs first 30 sec of the tobacco phase) and habituation
(last 30 sec vs first 30 sec of tobacco phase) were defined through contrast calculations.
206
Results: While BMI, current craving for sweets (VAS scale), hunger (VAS)
and time since the last meal were without effect on the reactivity, the
effect of the factor age class was significant with regard to the initial
cue reactivity (F(3)=5.52; p=0.001) and habituation (F(3)=5.25; p=0.002).
The contrasts between the children and each of the 3 other age groups
were significant (for all contrasts p<0.005)
Conclusion: While childrens psychophysiological activation seem not to
habituate in front of sweets, adolescents and adults reactions fade out
within few minutes. As a possible explanation one can hypothesize a
more developed cognitive control over the reactivity from adolescence on.
P-10-06
COMT val158met polymorphism is associated with coldpain response in Chinese heroin-dependent subjects
Alfreda Stadlin
Griffith University, School of Medical Science, Southport, Australia
Ada M. C. Ho, Ben K. L. Cheung
Introduction: Opioid users were particularly sensitive to cold-pressor
pain than other forms of pain induction methods such as mechanical
pressor and electrical stimulation. It has been suggested that chronic opioid administration can induce cold-pain hyperalgesia (Doverty et al.
2001). The present study aims to examine whether pain threshold and
tolerance are different between heroin-dependent subjects and controls
in a Chinese population. The COMT val158met polymorphism has been
shown to be associated with substance abuse as well as pain response.
This study further attempts to explore this correlate.
Method: Thirty-seven male Chinese subjects who fulfilled DSM-IV criteria for heroin-dependence and 63 age-matched healthy male subjects
with no history of substance use were recruited as controls. Cold-pressor
test was administered to all participants to ascertain both pain threshold
and tolerance. Subjects provided blood samples for DNA extraction.
Results: Results showed that pain tolerance of controls was significantly
higher than heroin-dependent subjects (P = 0.022) although no significant difference in pain threshold was observed. Pain tolerance/threshold
(tol/thr) ratio of heroin-dependent subjects was significantly lower than
controls (P < 0.0001). COMT val allele frequency of all subjects was
>70%. The val allele is shown to be associated with a lower pain tolerance and threshold in a gene dosage-dependent manner in all subjects
studied with heroin-dependent subjects having a significantly lower
tol/thr ratio when compared to controls (P=0.001).
Conclusion: This study suggested that COMT val158met may be influential in the temporal summation of pain, thus further suggests that
although the val allele is associated with a lower total pain tolerance (the
total time exposed to the painful environment) and a lower pain threshold (i.e. higher pain sensitivity), it is actually associated with the maintenance of a high net pain tolerance in healthy controls, which may be disturbed by chronic opioid administration. This may in turn affect the pain
maintenance of heroin-dependent subjects.
References: Doverty M. et al. (2001) Pain 93, 155-163.
P-10-07
Facets of impulsivity in club drug use: Genetic and personality correlates in a chinese population
Alfreda Stadlin
Griffith University, School of Medical Science, Southport, Australia
Natalie Loxton, Venice LN Wan, Ben KL Cheung
Introduction: The present study investigated the relationship between
two biologically-based dimensions of impulsivity, reward drive and
rash impulsiveness, and the COMT and MAOA gene variants in Hong
Kong Chinese club drug users.
Method: 360 club drug users and 303 non-users completed measures
of rash impulsivity (Zuckermans Sensation Seeking Scale, Zuckerman,
1994) and reward drive (BAS Scales, Carver & White, 1994). A related
personality dimension, behavioural inhibition, was also assessed (BIS
scale, Carver & White). COMT and MAOA gene variants were studied to
explore their correlates with personality traits.
OTHER - Poster
Results: Club drug users were found to be more rash impulsive,

reward-driven and less inhibited than non-users in that drug users scored
significantly higher on the total Sensation Seeking Scale (SSS) and the SSS
disinhibition scale than non-drug users, they also scored higher on BAS
Fun seeking and BAS Drive. Drug users were also less behaviourally inhibited than non-drug users. Rash impulsivity (high SSS disinhibition score),
but neither reward drive nor behavioural inhibition, was associated with
poly-drug use and drug use across the border from Hong Kong into mainland China. Club drug users were also found to have a higher frequency
of the high-activity val allele of the COMT val158met polymorphism
(80.0%, p = 0.015) when compared to controls (73.6%). Presence of the
COMT val allele was also associated with lower BAS drive in drug users,
In female club drug users, the frequency of the 941T allele of MAOA
(50%, p = 0.01) was higher than in controls (37%); no difference was
found in the male users. MAOA gene variant in the female is also associated with lower behavioural inhibition.
Conclusion: These findings suggest that while those who use club drugs
are generally more impulsive, more fine-grained impulsivity facets are
associated with differing patterns of drug use behaviour. Further, that
individuals with COMT and MAOA gene variants are associated with
impulsivity and inhibition, perhaps rendering these individuals more predisposed to experimenting with club drugs.
References: Zuckerman M (1994) Behavioral expressions and biosoical
bases of sensation seeking. Cambridge, England: Cambridge. Carver SC
& White TL (1994) Journal of Personality and Social Psychology 67:319333.
P-10-08
Suicidal thoughts among psychiatry residents with burnout
Frank van der Heijden
Vincent van Gogh Institute, Psychiatry, Venray, Netherlands
Gea Dillingh, Arnold Bakker, Jelle Prins
Introduction: Medical residents have a high risk for developing burnout,
since they are confronted with high job and educational demands, and
only few resources. The syndrome has been shown to have enormous
consequences, particularly when it is severe, including serious mental
health problems such as depression. Moreover, recent overviews indicate
an increased suicide rate in physicians and medical students. Therefore we
have performed a nationwide study to investigate the prevalence of
burnout and its relation with suicidal thoughts among medical residents
in The Netherlands.
Method: All Dutch medical residents (n = 5126; 52% is female) who
were in training on October 1st 2005 received a self-report questionnaire.
Burnout was measured with the Dutch version of the Maslach Burnout
Inventory Human Services Survey. Residents were asked about the frequency of suicidal thoughts with the question: Did you experience suicidal thoughts during your residency period?.
Results: Response rate was 41.3% (n = 2115). The age of the respondents varied between 23 and 58 years (mean= 31.5; SD=3.5). Highest
numbers came from internal medicine (14%, n = 292) and psychiatry
(11.5%, n = 242). A total of 432 residents (20.6%) were classified as having burnout. Twelve percent (n = 240) of all the participants reported having suicidal thoughts at least 1 time during their residency. Suicidal
thoughts were significantly associated with burnout (p < .01).
Furthermore, psychiatry residents most frequently reported suicidal
thoughts (significant versus all 26 medical specialties; p < .001).
Conclusion: The prevalence of suicidal thoughts among Dutch medical
residents is high. Suicidal thoughts are associated with burnout.
Particularly psychiatry residents are at risk.
P-10-09
Suicide ability and nightmares in mayor depression
Isabel Barros
Psichiatry, Santiago de Chile, Chile
Florenzano Ramon, Jadresin William
Introduction: Insomnia and nightmares are associated to depressive
symptoms and suicide ability. The SEROTONI NERGIC mechanisms would
be involved in regulating sleep and in the production of depressive symptoms and suicide.
Objective: Look for the association between nightmares and suicide ability in patients with mayor depression and describe their experiences from
the proper patients perspective
Method: We interviewed profoundly 12 woman from the Hospital del
Salvador who are under treatment for mayor depression chosen by intention. The database is analyzed using the method of Fundamated Theory.
Results: Through codification in first place the interview was analyzed.
Through codification in second place, the information was interpretated
and four themes were chosen for discussion: Depresive Simptoms, Suicide
Ability, Trauma, Nightmares and their meanings to the patients. 42% of
the interviewed present suicide intent (all describe nightmares). 60% of
them had trauma backround and their dreams are related to this.
References: 1. Bernert, RA, Joiner, TE, 1.Bernert, RA, Joiner, TE,
Cukrowicz KC, Schmidt NB, Krakow B. Suicidality and sleep disturbances.
Sleep 2005;28:1135-41 2.Sabo E, reynolds CF, Kupfer DJ, Berman SR.
Sleep, depression, and suicide. Psychiatry Res 1991;36:265-77 3. Benson
KL, FaullK, Zarcone VP. The effects of age and serotononergic activity on
slow wave sleep in depressive illness. Biol Psychiatry 1993;33:842-4
P-10-10
Epidemiology profile in suicide behaviour
Eugenio Chinea
Hospt Univ. de Canarias, Servicio de Psiquiatria, La Laguna, Spain
R. Gracia, M. Henry, C. Morales, D. Daz, I. Fernndez
Introduction: Analysing descriptive sociodemographic features in
patients with suicide behaviour attended in a general hospital emergency
ward, creating a data base for clinical study of suicide behaviour in our
community.
Methods: Suicide behaviour in a sample of 1000 suicide behaviour emergencies in 2003 through 2004 was studied. 18 epidemiology variables
and 2 clinical variables were considered.
Results: Mean suicide behaviours 1.3 per day. Intersex differences, male/
female 1/1.5. More frequent at age 20-40, mean age 34.2. Marital status, predominantly single. Primary education, with a job. Half of them
with a positive history of sucide behaviours, 35% had repeated in the last
year. On tueday (most frequent week day), in the afternoon, 12-6 p.m.
Mainly deliberate non-lethal attempts, not seeking death aranged with
security means. Most of them refered to a community mental health facility. More frequent diagnoses, Adjustment disorder, depression, and personality disorders. Main comorbility with substance use. Rather passive
methods, with psychotropic drugs.
Conclusion: Profile, 34 y.o. women, single, with a job, previous suicide
atempts, in the afternoon, on tueday, with pychotropic intoxication, lowmedium suicide intention, refered to a mental health facility with depressive adjustment disorder as diagnosis
P-10-11
Comparison between prevalence and severity of cognitive
dysfunctions among tick borne encephalitis patients in an
acute phase of the neuroinfection and three month later
Dariusz Juchnowics
Medical University Bialystok, Dept. of Psychiatry, Choroszcz, Poland
Anna Agnieszka Tomczak
Introduction: The objective of the study was evaluation of the frequency
an severity of cognitive dysfunctions in an acute phase of tick-borne
encephalitis (TBE) and three months later. Earlier studies indicated higher
occurrence of cognitive dysfunctions in TBE patients.
Method: We examined TBE patients two times. The first examination was
performed during their hospitalisation at Infectious Department of
Medical University in Bialystok and infectious wards in Hajnowka and
Bielsk Podlaski (North-Eastern Poland). The second examination was conducted three months after an acute phase of the neuroinfection- all of
subjects during the second examination were outpatients. There were 51
subjects - 31 men and 20 women; ages: 21 to 74 (average 44.8). TBE was
serologically confirmed in all examined patients. Subjects did not receive
any psychiatric care before the onset of the neuroinfection. They were
evaluated according to the Mini Mental State Examination (MMSE),
Reitans Trial Making Test (TMT) and Choynowsky Memory Scale. 31 con-
207
OTHER - Poster
trol healthy subjects were also examined two times with three months
interval.
Results: TBE patients had significantly more cognitive dysfunctions in the
first and the second evaluation in comparison to healthy subjects. Most
of cognitive deficits manifest themselves as mild cognitive disorder or
dementia. Among the most frequent cognitive dysfunctions were attention deficits, short term memory deficits, long term memory deficits and
visual memory deficits.
Conclusion: TBE patients should be examined by psychiatrist and often
need psychiatric treatment.
P-10-12
Efficacy of using plasmopheresis in treatment of mental
disorders
Marat Assimov
Pavel Shein, Anastasiya Kurbanova
Introduction: Modern psychopharmacological drugs besides positive
features have negative ones: side effects and resistance. This fact
demands searching for other methods.
Method: In this research work we examined the efficacy of using plasmopheresis (PP) among patients whose getting psychopharmacotherapy
(PFT) during 6 weeks was not effective enough. Registration of psychopathological symptoms was realized with the helping of CGI, HAM-D
and BPRS. The group of patients that were getting plasmopheresis consisted of 50 people. According to ICD - 10: 13 patients with F20.0;
20 patients with F25; 5 patients with F31, 12 patients with F33.
Results: Using combination PP with cPPT showed strong therapeutic
effect in 36% of cases and in 50% of cases therapeutic effect was medium (according to CGI) . Conducting PP caused strong therapeutic effect
among patients with apathic and melancholic depressions. Using this
method in the groups of patients with hypohondriac depressions was less
effective. Patients with anxiety depression showed increasing of symptoms after PP. Factorial analysis according to HAM: PP decreased 29% of
affective symptoms and 23% of somatic ones. Decreasing slow reaction- from 1,6 0,2 till 0,2 0,1 and work and activity - from 2,2
0,1 till 0,8 0,1.
Conclusion: Using PP among patients getting PPT can be used as a
method activating effect of modern psychopharmacological drugs.
P-10-13
Description of a transsexuals voice characteristics:
A case study
Andrea Lotto
IPQ HC FMUSP, GRUDA, Sao Paulo, Brazil
Maria Gabriela Cunha, Luis Antonio P. de Figueiredo, Ricardo Alberto
Moreno
Introduction: The transsexual has a sexual identification disorder and
even taking estrogens, the genetic male patient results basically in physical female appearance but still sustain a strong and not compatible voice,
as it should be, a female voice to female body. The present study aimed
to describe the voice characteristics of a transsexual patient from a voice
ambulatory and tried to identify functional aspects which are involved in
this transformation.
Method: The perceptive-auditory parameters were evaluated in one
transsexual patient: A.M.S., 25 years old, without any kind of surgery
(sex, vocal) from the Voice Ambulatory at Hospital das Clnicas
Otorhinolaryngology Department-University of So Paulo Medical School
(HC ORL FMUSP). It was used the CAPE_ASHA 2004, SID 3 ProtocolPerceptive-Auditory Voice Evaluation Consensus (Behlaus translation);
Vocal Profile Evaluations Protocol (Behlau, 2000).
Results: The voice complaint was basically about the very low in pitch
and problems with social life. The patients vocal characteristics findings
were also: poor vocal inflections/ variations, speech in blocks, short phrases,
propensity to nasality and oppressed larynx - pharynx resonance, intonation out of context.
Conclusion: Despite of psychiatric and psychotherapy treatment be recognized as essential, if the vocal qualities do not be compatible with the
208
physical appearance, the patient can create inappropriate way of leading

with this problem. According to Coleman (1983), the voice is the most
resistant genders characteristics sensitive to changes. So, a proper voice
therapy can contribute to develop a better voice and life quality condition
to this patient.
References: American Psychiatric Association. Manual Diagnstico e
Estatstico de Transtornos Mentais (DSM-IV TR). 4a Ed.Porto Alegre: Artes
Mdicas, 2000. Behlau, M. Voz. O Livro do Especialista.Ed. Revinter, VOL
II, Rio de Janeiro, 2005 Sataloff R. Professional Voice: The Science and art
of Clinical Care. Raven Press, New York, 1991. Organizao PanAmericana da Sade e Organizao Mundial de Sade. Relatrio sobre a
Sade no Mundo 2001. Sade Mental: Nova Concepo, Nova
Esperana. Disponvel na Internet em http://www.whr@who.int Phillips,
M.A. Developing a female voice. The transgender support site. Internet:
http://heartcorps.com/journeys/, 17p. 1998.
P-10-14
Formal caregivers of dementia patients: Global descriptive
profile
Patricio Fuentes
Psychogeriatric Unit, Mental Health Service, Santiago, Chile
P. Alegria, L. Olavarria, C. Olave, S. Vega
Introduction: Exists insufficient characterization of the global profile of
the professional caregivers of patients with dementia. The objective of
this study was to characterize in a multidimensional way to a group of
caregivers of inpatients with dementia and related disorders in a medium
stay psychogeriatric clinic.
Method: 20 professional caregivers were evaluated using a general
knowledge test about dementia, the Zung anxiety scale, the P.E.N.L.
(Eysenck) questionnaire of personality, Dominoes Intelligence test and an
individual interview that included personal antecedents and motivation to
the work. The patients were diagnosed according to the DSM-IV criteria.
80% of the patients corresponds properly to dementia, of which 52.9%
is Alzheimer type. The care of the patients is distributed by work shifts,
assigning 6 patients for day to each caregiver.
Results: The 20 caregivers are women, age average 50,11 years (SD 5.9),
education level 10,63 years (SD 3,62), previous experience in the care of
dependent patients of 6,89 years (SD 5,45). Of these caregivers 60% had
received some type of specific training. 78,9% of the caregivers knew
that the main disorder of the unit is the dementia, nevertheless 57.8%
doesnt understand the concept of the syndrome. 5,2% of the caregivers
accepts that the global stimulation of the patient should be included
among their daily tasks. 47.3% of them points out that the intervention
stimulation is only to have patience and to give affection, while 15.7% of
them associates it with fomenting the patients autonomy.
Complementarily data will be presented about level of anxiety, labor motivation, intellectual coefficient and personality traits of these caregivers
Conclusion: This study suggests that professional caregivers of dementia
patients, still when they have important previous labor experience, reveal
insufficient knowledge about the illness that they attend and evidence
particular personality traits and motivation toward its work
P-19
Other II
T12 Other
P-19-01
Plasma cytokine profiles in depressed patients who fail to
respond to selective serotonin reuptake inhibitor therapy
Sinead OBrien
St Annes Day Hospital, Psychiatry, Cork, Ireland
Paul Scully, Peter Fitzgerald, Lucinda V. Scott, Timothy G. Dinan
Introduction: Approximately 30% of patients with depression fail to
respond to a selective serotonin reuptake inhibitor (SSRI). Few studies
have attempted to define these patients from a biological perspective.
OTHER - Poster
Studies suggest that overall patients with depression show increased production of proinflammatory cytokine. We examined pro- and anti-inflammatory cytokine levels in patients who were SSRI resistant.
Method: Plasma concentrations of IL-6, IL-8, IL-10, TNF-a and sIL-6R
were measured with enzyme linked immunosorbent assays (ELISA) in
DSM-1V major depressives who were SSRI resistant, in formerly SSRI
resistant patients currently euthymic and in healthy controls.
Results: Patients with SSRI-resistant depression had significantly higher
production of the pro-inflammatory cytokines IL-6 (p=0.01) and TNF-a
(p=0.004) compared to normal controls. Euthymic patients who were formerly SSRI resistant had proinflammatory cytokine levels which were similar to the healthy subject group. Anti-inflammatory cytokine levels did
not differ across the 3 groups.
Conclusion: Suppression of proinflammatory cytokines does not occur in
depressed patients who fail to respond to SSRIs and is necessary for clinical recovery.
P-19-02
Impact of gender and menstrual cycle phase on plasma
cytokine concentrations
Sinead OBrien
St Annes Day Hospital, Psychiatry, Cork, Ireland
Peter Fitzgerald, Paul Scully, Anne M.T. Landers, Lucinda V. Scott,
Timothy G. Dinan
Introduction: The lifetime prevalence of major depression is twice as
high in females as compared to males. Depression is known to increase at
periods where there are changes in gonadal hormones. We examined
pro- and anti-inflammatory cytokine levels during the normal menstrual
cycle of healthy females as compared to similar time points in healthy
males.
Method: Plasma concentrations of IL-4, IL-6, IL-8, IL-10, TNF-a and sIL-6R
were measured with enzyme linked immunosorbent assays (ELISA) in
healthy females during the normal ovulatory menstrual cycle and also in
males at similar time-points.
Results: The luteal phase of the menstrual cycle is associated with
increased production of sIL-6R, IL-4 and TNF-a as compared to the early
follicular phase. No change was observed in IL-6, IL-8 and IL-10 concentration throughout the menstrual cycle. We found IL-4 positively correlated
with oestrogen while TNF-a positively correlated with progesterone.
Females were found to have significantly higher concentrations of TNF-a
and sIL-6R across all phases of the menstrual cycle, as compared to males
across similar time-points.
Conclusion: The normal menstrual cycle is associated with increased production of sIL-6R, IL-4 and TNF-a in the luteal phase as compared to the
early follicular phase. Females have significantly higher concentrations of
sIL-6R and TNF-a at all time points across the menstrual cycle as compared
to males.
P-19-03
PMS and its relationship with previous abuse experince
and dissociative symptoms
Shinyoung Suh
College of Medicine, Cha Univ., Dept. of Psychiatry, Sungnam-si,
Kyonggi-do, Republic of Korea
Introduction: It is postulated in this study that the severity of characteristic of PMS is more dependent on psychological factor than biological
factors. It can be further postulated that symptom severity of PMS is associated with dissociative symptoms. Since traumatic event are known to be
related to dissociative symptoms. The purpose of this study is to find out
the association of PMS symptom severity with previous abuse history and
dissocitive symptom.
Method: Subject for this study were 377 nurse, out of which 183 subjects submitted valid data. The presence and the symptom severity of PMS
were rated using Daily Record of Severity of Problem.(DRSP) and
Shortened Premenstural Assesment Form(SPAF). Dissociative symptom
were evaluated Dissociative Experience Scale Korean version(DES-K)
Results: Subject were divided into 3group as no PMS, mild to moderate
PMS and severe PMS group. There was a statistically significant difference
in DES-k total abuse scale among 3group. Pysical/verbal abuse scale, sexual abuse scale and parental spouse abuse scale also revealed a stastistically significant differnence among the 3 group.
Conclusion: The symptom severity of PMS using SPAF total score showed
a positive correlation both with degree of dissociative experience and previous abuse experience. There was a statistically significant difference in
both dissociative experience and previous abuse experience among
the3groups. These results indicate that there can be a possible association
among PMS symptoms, dissociative symptoms, and previous psychologically traumatic experience.
References: Richards M, Rubinow DR, Daly RC, Schmidt PJ. Premenstrual
Symptoms and Perimeonpausal Depression. Am J Psychiatry 2006;
163:133-137 Connolly M. Premenstrual syndrome: an update on definitions, diagnosis and management. Advance in Psychiatric Treatment
2001; 7:469-477
P-19-04
Premestrual syndrom and its relationship with previous
abuse experience and dissociative symptoms
Shinyoung Suh
College of Medicine, Cha Univ., Dept. of Psychiatry, Sungnam-si,
Kyonggi-do,Republic of Korea
Introduction: It is postulated in this study that the severity of characteristic of PMS is more dependent on psychological factor than biological
factors.It can be further postulated that synptom severity of PMS is associated with dissociative symptom. In this study, we tried to find out the
association of PMS symptom severity with prevous abuse history and dissocitive symptom.
Method: Subject for this study were 377 nurse,out of which 183 subjects
submitted valid data.the presence and the symptom severity of PMSwere
rated using Daily Record of Severity of Problem.(DRSP) and Shortened
Premenatural AssesmentForm(SPAF).Dissociative symptom were evaluated
Dissociative Experience Scale korean version(DES-K)
Results: Subject were divied into 3group as NoPMS,mild to moderate
PMS and Severe PMS.There was a statistically significant difference in
DES-k total ause scale
Conclusion: Symptom severity of PMS using SPAF total score showed a
positive crrelation both with degree of dissociative exprience and previous
abuse experience. There was a statistically significant difference in both
dissociative experience and previous abuse experience among 3 groups.
These results show that there can be a possible association PMS symptoms, dissociative symptoms, and previous psychologically traumatic
experience.
References: Richards M, Rubinow DR, Daly RC, Schmidt PJ. Premenstrual
Symptoms and Perimeonpausal Depression. Am J Psychiatry 2006;
163:133-137 Connolly M. Premenstrual syndrome: an update on definitions, diagnosis and management. Advance in Psychiatric Treatment
2001; 7:469-477
P-19-05
A comparison of tridimensional personality questionnaire
(TPQ) in premenstrual dysphoric disorder and major
depressive disorder
Chia-Yih Liu
Chang-Gung Hospital, Department of Psychiatry, Kweishang, Taoyuan,
Taiwan
Mei-Chun Hsiao
Introduction: The unified biosocial model of the Tridimensional
Personality Questionnaire (TPQ) is composed of three independent heritable dimensions of temperament-novelty seeking (NS), harm avoidance
(HA), and reward dependence (RD). Several studies have found that major
depressive disorder (MDD) is associated with high score on the HA dimension. Using the TPQ in women with premenstrual dysphoric disorder
(PMDD) is rare. The study was designed to examine the relationship
among MDD, PMDD and normal subjects in women by the biosocial
model.
209
OTHER - Poster
Method: The subjects were 149 women including patients in our clinic
and our medical staffs. All people were assessed by means of the TPQ and
DSM-IV to confirm the diagnosis.
Results: The average of age was 33.37.3 years and education
was14.32.7 years. Of the 149 subjects, 51(34.2%) had MDD, 45
(30.2%) had PMDD, and 53(35.6%) were normal control group. Age and
education in MDD group differed significantly than PMDD and normal
subjects (one way ANOVA age, p= .004; education, p= .000). Adjusted
the influences of age and education, PMDD and MDD groups had the
higher NS scores than normal group (ANCOVA p= .000).
Conclusion: Elevations of HA dimension was associated with a tendency
for the PMDD to present the same psychopathology as MDD. Further
research might focus on the different symptoms to clarify the possibility
of the differential subtypes of PMDD.
References: 1. Cloninger CR. A systematic method for clinical description
and classification of personality variants: a proposal. Arch Gen Psychiatry
1987;44:573-588 2. Farabaugh A, Ongur D, Fava M, Hamill SK, Burns
AM, Alpert J. Personality disorders and the trimensional personality questionnaire factors in major depressive disorder. J Nerv Ment Dis
2005;193:747-750. 3. Hsiao MC, Liu CY, Chen KC, Hsieh TT.
Characteristics of women seeking treatment for premenstrual syndrome
in Taiwan. Acta Psychiatr Scand 2002;106:150-155.
P-19-06
1h-MRS measurements of glutamate levels in premenstrual
dysphoric disorder
Neha Batra
University of Alberta, Dept. of Psychiatry, Edmonton, Canada
Janette Seres, Chris Hanstock, Peter Seres, Peter Allen, Glen Baker,
Janisse Khudabux, Jean-Michel Le Melledo
Introduction: Premenstrual dysphoric disorder (PMDD) is a clinical syndrome characterized by moderate to severe alterations in mood, behaviour and physical well-being that impairs the personal, professional and/or
social functioning of 5 to 7% of premenopausal women. Classical symptoms include anxiety, sadness, and irritability. Several studies illustrate the
association between PMDD symptomatology and the normal fluctuation
of female hormones and their metabolites in PMDD women. In this context it is worth noting that both progesterone and estrogen, and their
associated metabolites influence glutamate and gamma-aminobutyric
acid (GABA) system neurotransmission in the brain. Both glutamate and
GABA play a major role in symptoms of anxiety and depression.
Glutamate is the major excitatory neurotransmitter in the brain cortex and
its action is counterbalanced by the inhibitory action of GABA. Advances
in proton magnetic resonance spectroscopy (1HMRS) allow for the direct,
non-invasive and in vivo measurement of brain metabolite concentrations
in specific brain regions of interest. Glutamate was examined in vivo in
the medial prefrontal cortex (MPFC) of women who suffer from PMDD
and healthy controls (HCs) during the follicular phase (FP) and the luteal
phase (LP) of menstrual cycle (MC).
Method: Diagnosis of PMDD was made according to DSM-IV criteria and
following prospective daily monitoring of premenstrual symptoms for 2
consecutive menstrual cycles. 12 PMDD and 13 HCs were randomized to
two single-voxel 3T 1HMRS examinations of the medial prefrontal cortex
in the FP and the LP.
Results: In HCs, the Glx/Cr levels were 5.862.30 and 4.851.34 in FP
and LP, respectively. In PMDD women, Glx/Cr levels were 6.141.49 and
4.511.15 in FP and LP, respectively. There was a phase effect for Glx/Cr
(F(1,46)=7.96, p=0.007). There was no diagnosis effect (F(1,46)=0,
p=1.0) and no diagnosis by phase effect (F(1,46)=0.46, p=0.50).
Conclusion: Our preliminary results suggest that the hormonal fluctuations associated with the MC alter the glutamate levels. Our current
results suggest that despite undergoing a similar menstrual-related fluctuation of brain glutamate levels as HCs, PMDD women may display an
increased behavioural sensitivity to those phase related alterations.
210
P-19-07
Assessing symptoms of depression in narcolepsy patients
with and without cataplexy
Cecilia Jara Opazo
Sleep Disorders Center, Psychiatry U. Regensburg, Germany
P. Geisler
Introduction: Depressive symptoms are commonly reported by literature
in patients with Narcolepsy. The objective was to assess depression in
these patients and furthermore to compare depression scores in patients
with and without cataplexy.
Method: Sixty-two patients with narcolepsy were seen for psychological
testing. Age between 20 and 74 years, 30 female and 32 male. They
completed Beck Depression Inventory (BDI), Zung Self-rating Depression
Scale (ZSDS), Numeric Subjective Depression Scale (NSDS) and Epworth
Sleepiness Scale (ESS). All the patients were in pharmacological treatment
for Narcolepsy. Descriptive statistics were performed using SPSS 14.0 for
Windows. The presence of depressive symptoms was based on the cut off
points of BDI and ZSDS.
Results: In BDI (score: 0-9 normal, 10-17 dysphoria, 18-20 depressive
symptoms, 20 or more depression) the percentage of patients without
any depression symptoms was 58 % , with dysphoria 21%, depressive
symptoms 3,2% and depression 14,5%. In ZSDS (score: 20-39 normal,
40-47 mild depression, 48-55 moderate depression and 56-80 severe
depression) the percentage of patients in the normal range was 58.1%,
mild 24%, moderate 9,7% and severe depression 6,5%. The percentage
of narcolepsy patients with a pathological score in the ESS (=12 points)
was 90%. Was no significant correlation between hypersomnia (according ESS) and depression (according ZSDS and BDI) using Kruskall-Wallis
test (Chi square=0.524, df=2, p=0.770). In NSDS (score 0-3 no depressive
feelings, 4-7 feel depressed, 7-10 feel very depressed) the percentage of
patients who do not report depressive feelings was 58%. The subgroup
with Narcolepsy-cataplexy in comparison with Narcolepsy without cataplexy, using Mann-Whitney test, showed no significant difference in the
depressive symptoms.
Conclusion: The prevalence of manifest depression was relatively low,
compared to earlier results, but many patients experience some symptoms of depression. This cannot be attributed exclusively to an overlap
between typical symptoms of Narcolepsy and depressive symptoms in the
scales of depression, because a similar proportion of depression is found
in the NSDS, where no specific symptoms are asked for.
P-19-08
Comparison of narcolepsy with Cataplexy and without
Cataplexy - clinical variables, HLA-DQB1*0602 and
Hypocretin Sung-Pil Lee
St.Vincent Hosp, Catholic Univ, Psychiatry, Suwon, Republic of Korea
Jong-Hyun Jeong, Seung-Chul Hong, Jin-Hee Han, Yoon-Kyung Shin,
ChungTai Lee
Introduction: Narcolepsy is a sleep disorder, characterized by excessive
daytime sleepiness, cataplexy, sleep paralysis, and hypnagogic hallucination. Among these symptoms, cataplexy is one of the most pathognomonic symptoms in narcolepsy. This study was designed to investigate the
clinical features, frequency of DQB1*0602 and CSF hypocretin levels in
Korean narcoleptics with cataplexy to compare with those who have not
cataplexy.
Method: From August 2003 to July 2005, we selected 72 patients who
have narcolepsy confirmed by nocturnal polysomnography and multiple
sleep latency test(MSLT) as well as their history and clinical symptoms at
Sleep Disorders Clinic of St. Vincents Hospital, the Catholic University of
Korea. The patients were divided into 56 cataplexy-positive group(narcolepsy with cataplexy group) and 12 cataplexy-negative group(narcolepsy
without cataplexy group). All patients have done HLA typing for the presence of DQB1*0602 and received spinal tapping for measuring the level
of CSF hypocretin. Clinical variables were examined by semi-structured
interview for narcolepsy patients.
Results: 1. In cataplexy-positive group, compared with cataplexy-negative group, the frequency of HLA-DQB1*0602 was found to be significantly increased(50 subjects, 89.3% vs. 8 subjects, 50.0%)(P=0.000).
OTHER - Poster
2. In 48 out of 56 cataplexy-positive patients(85.7%), hypocretin levels

were decreased(=110 pg/ml) or below the detection limit of assay(<40
pg/ml). However, only 6 out of 16 cataplexy-negative patients(37.5%)
exhibited decreased hyopcretin level. And the difference between two
groups were statistically significant(P=0.000). 3. Cataplexy-positive group,
compared with cataplexy-negative group, reported more frequent hypnagogic hallucinations(36 subjects, 64.3% vs. 4 subjects, 25.0%)
(P=0.005). However, there were no significant differences in frequency or
severity of daytime sleepiness, sleep paralysis and demographic data. 4.
In nocturnal polysomnography and MSLT findings, there were no significant differences in all sleep parameters between two groups.
Conclusion: Higher frequency of HLA-DQB1*0602, and lower hypocretin levels in cataplexy-positive groups, than catapelxy-negatives, suggest
that narcoleptics with cataplexy might be a etiologically different disease
entity from narcoleptics without cataplexy. Additionally, Current criteria
prevail for the diagnosis of narcolepsy need to be reclassified according to
the presence of cataplexy or not.
References: 1) Aldrich MS. Narcolepsy. N Eng J Med 1990;323:389-394.
2) Bassetti C, Aldrich M. Narcolepsy. Neurol Clin 1996;14:545-571.
P-19-09
Comorbid interrelations in depressions, alcoholism and
sexual dysfunctions in men
Georgy Dremov
Mental Health Institute, Sexological Service, Tomsk, Russia
Evgeny Schastnyy, Nikolay Bokhan
Introduction: Sexual disorders in depressions, comorbid with alcoholism,
are determined by interaction of severity of depressive manifestations,
frequency and duration of phases and remissions, severity of alcohol
dependence, personality peculiarities as well as peculiarities of psychosexual development. Depression may evoke sexual disturbances and vice
versa. Clinically outlined depressions requiring medical intervention are
observed in 50 % of persons, suffering from alcoholism.
Objective: To distinguish totality of significant constitutional-biological
factors for identification of prognosis, course and development of methods of treatment of comorbid depressive, addictive and sexual disorders.
Method: In clinics of Mental Health Research Institute 42 men with
depressive, addictive and sexual disorders (25-55 years) have been examined. Examination was conducted with psychopathological method,
method of structural analysis of sexological disorders, statistic method.
Three psychological variants of depression have been distinguished: vital
depression, characterized by anguish and apathy (25%), reactive
depression, characterized by actual psychogenic experiences (30%),
depression of exhaustion, for which asthenic, psychosomatic manifestations (45%) are typical. Depressive disorders were combined with alcohol dependence in 38 % of cases.
Results: In mild (ICD-10: F43.2, F32.0: HDRS - 10 scores; 50%) and moderate (ICD-10: F32.1; HDRS - 16 scores; 30%) depressive disorders, sexual dysfunctions may be regarded as a common clinical radical in depressions in men. Thereby, comorbidity of depressions with alcohol dependence increased up to 42 %., and prevalence of sexual dysfunctions
reached 75 %. They manifested themselves in decrease of libido (75%),
erectile dysfunctions (68%), ejaculatory (22%) and orgasmic disturbances
(15%). In severe depressive states (ICD-10: F.32.2: HDRS - 25 scores; 20%
of patients) sexological disturbances digress from the foreground, sexual
life disactualizes.
Conclusion: After restoration of mental state in depressive and addictive
patients, sexual disturbances often remain. In this association program of
treatment and rehabilitation of patients with comorbid depressions,
addictive and sexual disorders with preparation LEVITRA (vardenafil) has
been developed allowing realization of the principle of complex biopsychosocial model, considering this pathology as multi-factorial disorder.
P-19-10
A comparison of the mmpi -2 among transsexuals across
gender and sex-reasignment stage
Angela Vidal Hagemeijer, Manuel Salamero Baro

Introduction: Transsexual patients show noticeable levels of psychological distress that may result from multiple stressors, including frequently
familiar and social reject, employment problems and economical and legal
difficulties for sex reassignment. The purpose of the present study is to
assess psychopathology using the MMPI-2 across Spanish transsexuals
seeking for sex-reassignment.
Method: Minnesota Multiphasic Personality Inventory-2 (MMPI-2) was
administered to 161 sex change applicants who had been diagnosed as
transsexualism (ICD-10 and DSM-IV-TR criteria). The sample was divided
in groups according gender (n=107 male to female (M-F) and n=54
female-to-male transsexuals (F-M)), and each gender group according sex
reassignment stage (transsexuals requesting sex reassignment hormonal
therapy (SRHT) (n=37 M-F and n=44 F-M) and transsexuals requesting sex
reassignment surgery (SRS) (n=69 M-F and n=10 F-M)).
Results: Mean T scores from the MMPI-2 were within the normal range
except for the Masculinity-feminity (M-f) scale. M-F transsexuals did not
differ significantly in mean T clinical scores nor in the percentage of
patients with T=65 from the F-M transsexual group. In the M-F group,
compared with patients seeking for SRS, individuals seeking for SRHT
trend to score higher in all scales, and score significantly higher in scales
Depression (D), Hysteria (Hy), Psychopathic Deviate (Pd), Paranoia (Pa),
Psychasthenia (Pt), and Social Introversion (Sc). In the F-M group significant differences are found only in Pt scale. Nevertheless, both groups neither demonstrated any significant elevations on all the clinical scales other
than on Mf scale.
Conclusion: Results support the view that 1) transsexuals candidates to
sex reassignment were notably free of psychopathology, 2) M-F did not
differ from F-M in degree of psychopathology, and 3) a large number of
M-F transsexuals in the first stages of sex reassignment may experience
more psychological distress than patients in the last stages, but the results
are unlikely to reflect clinically relevant differences.
References: Miach P, Berah E, Butcher J, Rouse S. Utility of the MMPI-2
in assessing gender dysphoric patients. Journal of Personality Assessment
2000; 75: 268-279. Michel A, Ansseau M, Legros JJ, Pitchot W, Cornet JP,
Mormont C. Comparisons of two groups of sex-change applicants based
on the MMPI. Psychol Rep 2002; 91 (1): 233-240.
P-19-11
Personality traits among patients with chronic fatigue syndrome: An evaluation using the Cloninger Temperament
and Character Inventory (TCI)
Esther Gomez Gil
Fernando Gutierrez Ponce De Leon, Teresa Godas Sieso, Joaquin
Fernandez Sola, Jose Manuel Fernandez Huerta
Introduction: The cause of chronic fatigue syndrome (CFS) is poorly
understood. It has been hypothetized that personality may play a role in
the vulnerability to suffer this syndrome, however results are inconsistent
(Henderson and Tannock, 2004). The aim of this study is to assess the personality profiles of CFS patients,
Method: The sample include 100 patients with CFS (Fukuda criteria,
1994), remitted consecutively to a specialized Unit for this syndrome in
the Hospital Clinic of Barcelona. The personality profiles were examined
using the Cloningers Temperament and Character Inventory (TCI). Traits
were compared with Cloningers normal Community Sample, using both
Chi-squared and t-testing, with p < 0.05 taken as a level of significance.
Results: SRC patients were not significantly different than the community
sample in the average values with respect to the four Temperament and
three Character trait scores.
Conclusion: The TCI dimensions might not be considered as predictors of
fatigue chronic syndrome
References: Kane RL, Gantz NM, DiPino RK. Neuropsychological and psychological functioning in chronic fatigue syndrome. Neuropsychiatry
Neuropsychol Behav Neurol 1997; 10:25-31
Esther Gomez Gil

211
OTHER - Poster
P-19-12
Common mental disorders and medically unexplained
symptoms in family health units (primary care) in petropolis/Brasil
Sandra Fortes
FCM/UERJ, Psicologia Medica/DEM, Rio de Janeiro, Brazil
Javier Garcia-Campayo, Monica Campos, Claudia Lopes, Luiz Augustro
Villano
Introduction: Common Mental Disorder (CMD), mainly depressive and
anxiety disorders, are very frequent in Primary Care, usually being presented
as somatic symptoms. Medically Unexplained Symptoms (MUS) are very
frequent in Latin population, especially among those seen in general
health care. Brazil has created the Family Health Program (FHP) who is
responsible for primary care for 44,5% of the population, specially the
poorest ones, including mental heath interventions.AIMS: To detect CMD
and MUS prevalence and the type of the commonest medically unexplained complaints among the patients in FHP, and to study their association depending on the type of consultation.
Method: A survey among 714 patients attending doctors consultation in
five FHP units during one month was held in Petrpolis, Rio de Janeiro.
GHQ was used for CMD detection and CIDI for obtaining the positive
patients nosological profile. The doctors rated all symptoms presented by
these patients as somatic justified, medically unexplained or psychological
ones.
Results: CMD was present in 56% of the patients attending medical consultations in FHP, reaching 61% of those with new complaints but only
49% of group ones. MUS were present in 43% of patients with new
complaints, 52% in subsequent individual consultations and 40% of
those attending psycho educational groups for hypertension and diabetes
patients. They were the type of symptom most strongly associated with
CMD in new consultations, but they are also strongly associated with psychological symptoms. The most prevalent MUS were pain, pseudoneurologic symptoms and sleep problems. The nosological profile of the
patients with CMD revealed that 19% of them had a life time diagnosis
of Somatoform Pain Disorder and 20% of Dissociative Disorders, beside
Depressive and Anxiety Disorders.
Conclusion: MUS are very prevalent in primary care in Brazil and strongly
associated with CMD, revealing the importance of somatoform and dissociative disorders among this population. Regular and stable follow-up
with the FHP teams, especially using group interventions, seems to help
decreasing CMD prevalence.
References: - Araya R., Rojas G., Fritsch R., Acua J., Lewis G. Common
Mental Disorders in Santiago, Chile: Prevalence and Socio-Demographic
Correlates. Br J Psychiatry 2001;178: 228-33. - Garcia- Campayo J., Lobo
A., Perez-Echeverria MJ., Campos R. Three Forms of Somatisation
Presenting in Primary Care Settings in Spain. Journal of Nervous and
Mental Disorders 1998; 186:554-560. - Goldberg D., Huxley P. Common
Mental Disorders: a Bio-Social Model. 1992; Tavistock/ Routledge
London.
P-19-13
Mania secondary to brainstem infarction
Nedim Havle
Bakirkoy Research and Training, Hospital for Psychiatry, Istanbul, Turkey
Samuray Ozdemir
Introduction: An uncommon case of secondary mania due to brainstem
stroke in a patient is presented.
Method: A 50-year-old male patient was brought to the outpatient clinic
with complaints of aggressive behaviors existing for 2 weeks. He had
sleepness, excessive talking, increased religious activities, going on a
spending spree and quickness of temper. These complaints developed following a cerebrovasculary accident that affected ventral pons ten years
ago. There was neither past/family history of psychiatric disorder nor substance abuse/dependence. The patient has been experiencing similar
episodes every year, approximately 2 months in duration which were
being resolved spontaneously without any medication.
Results: Psychiatric examination revealed increased psychomotor activity,
irritable mood, grandiosity, pressured speech, flight of ideas and
increased religious thinking. There were no psychotic symptoms. Patient
212
had a mild left hemiparesis, left hemihypoesthesia and ataxic gait in neurologic examination. Routine blood tests and serological examinations
were within normal limits. Magnetic resonance studies demonstrated diffuse atrophy in brainstem and gliotic changes in ventral pons. The patient
is diagnosed with mood disorder due to a general medical condition with
manic features depending on DSM-IV. His symptoms were recovered with
400 mg/day carbamazepine treatment.
Conclusion: Injuries in right hemisphere lead to increased serotonin binding in undamaged regions which produce a biochemical compensation
for damaged areas. Poststroke mania is associated with brain regions
which have a connection to limbic cortex. Previous studies demonstrated
that frontal or basotemporal cortex injuries may induce compensatory
serotoninergic activity in limbic cortex. Furthermore, it has been shown
that brainstem also has subcortical connections, and injuries of it may
induce manic symptoms by affecting limbic systems. Secondary mania
which developed following ventral pontine infarction was reported previously. This case emphasizes the relationship between secondary mania
and stroke. Therefore, we suggest that brainstem disturbances have influences on mood.
References: Drake ME Jr, Pakalnis A, Phillips B. Secondary mania after
ventral pontine infarction. J Neuropsychiatry Clin Neurosci. 1990
Summer;2(3):322-5. Goyal R, Sameer M, Chandrasekaran R. Mania secondary to right-sided stroke-responsive to olanzapine. Gen Hosp
Psychiatry. 2006 May-Jun;28(3):262-3.
P-19-14
Psychiatric evaluation predictors of non-compliance in
renal transplantation: A six-year resaerch
Ximena Torregrosa
Via del mar, Chile
Caty Gonzales, Maybe Riveros, Hernan Borja, Rene Clavero, Christian
Videla, Beatriz Tapia
Introduction: A major cause of organ transplantation failure is the noncompliance with immunosupressive medication. The Renal Transplant
Program started including psychiatric evaluation of all patients with the
objetives in mind :1) Identify the risk factors associated to the future
transplantation failure due to emotional or behavioral problems, and 2)
Diagnose mental Disorders interfering with the patients evolution that
could be treated.
Method: 282 patients were evaluated by means of an instrument especially designed for rating behavior, cognitive and affective status and
trough psychosocial screening, between May 2000 and May 2006. Of this
group, 11 patients (3.9%) evidenced severe psychiatric disorder. This was
discussed by the transplant staff and the patients were rejected from the
program as they had a bad prognosis. 45 patients (15.9%) were found to
be affected by a disease that required treatment. The were put under psychiatric treatment and/or cognitive-behavioral psychotherapeutic treatment and then they were re-evaluated and entered the program later.
Results: Of the total of 67 transplanted patients, in six years, only one
patients abandoned immunosupressive medication and had acute rejection, losing her transplanted kidney.
Conclusion: This research found that psychiatric and psychological intervention in a renal transplant program allows to reduce the post-transplant
non-compliance risk and favor a better general adaptation level in the
patients.
OTHER - Poster
P-20
Other III
T12 Other
P-20-01
Role of physiogenic factors in genesis of borderline disorders
Valentin Semke
Mental Health Institute, Borderline States Department, Tomsk, Russia
Introduction: Psychogenia contributes to development of pathological
shifts in nervous system and internal organs; to complication of personality disorders.
Method: 154 combatants with PTSD aged 20-45 years have been examined. In clinical picture of initial period symptoms of general neurotic plan
prevail reflecting shifts in vegetative domain. Basic dysfunctional states
emerging in extreme conditions of combat setting, are mental disorders
of borderline level: neurotic - 91 persons (59,1 %), pathocharacterological - 43 (27,9 %) and neurosis-, psychopath-like - 20 (13,0 %).
Results: In the first group presence of cardiovascular pathology and
pathology respiratory ways has been revealed equally (11 %); in 9,9 % of
combatants ulcerous illness of the stomach and duodenal intestine has
been diagnosed. In the second reliably more frequently other illnesses
of GIT were found in 53,5 % (p<0,05), on the second place in incidence rate cardiovascular diseases were 16,3 %. In the third group in
45 % of cases cardiovascular pathology was diagnosed, in 20 % pathology of urino-genital organs. Confirmation of psychogenic origin of visceral-vegetative symptoms was severe therapeutic effect from individually
selected schemes of psychotropic preparations in complex with psychotherapeutic methods. Experience of medical assistance rendering for
combatants during combat actions in Afghanistan and the other hot
points of recent decades has shown that under conditions of local wars
along with mental disorders, peculiarities of course of visceral pathology
have been revealed: lowered resistance toward infections, growth of areactive forms of pathology and diseases against the background of allergization of the organism, more frequent development of chronic and
relapsing processes. This is why, along with neurometabolic, dehydrotating-absorbable, vascular, general-tonic therapy the special accent is put
on use of immunocorrection
Conclusion: As a whole, investigation of the role of somatic disorders in
pathogenesis of PTSD has allowed identification of its chronifying and
pathoplastic role in formation of clinical variants (to greater extent in the
third group, to lesser - in the first). Of great significance was correlation
of contribution of psychogenic factor of combat stress, constitutional-biological peculiarities of a combatant and influence of somato-organic
pathology.
P-20-02
Why immigrants visited at psychiatry emergency services
are not diagnosed as a borderline personality disorder?
Differences according to region of origin
Juan Carlos Pascual
Angeles Malagn, David Crcoles, Jose Mara Gins, Andrea Gabilondo,
Rosa Acea, Carlos Garca-Ribera, Antoni Bulbena
Introduction: The association between immigration and borderline personality disorder (BPD) has not been extensively investigated. Some studies have suggested that immigration could be a risk factor for mental
health disorders such as psychosis and that immigrants have higher rates
of psychiatric emergency service (PES) utilization than natives (1,2).
However, in some of these studies immigrant samples have been analyzed
as a single group, therefore not taking into account major cultural differences that depend on their region of origin. The aim of this study is to
examine the association between immigration and BPD diagnosis in the
psychiatric emergency unit and determine differences according to area
of origin.
Method: A total of 11578 consecutive visits at a tertiary hospital PES over

a 4-year period were reviewed. Data collected included socio-demographic, clinical, social and therapeutic information and the Severity of
Psychiatric Illness (SPI) score. The sample was divided in six groups: North
Africa, Subsaharian area, Southamerica, Asia, Western-origin (Europe,
North America and Australia) and natives.
Results: 1340 (11.6%) patients were immigrants: 35.8% Southamerican,
29.6% North Africa, 23.1% Western-origin, 7.9% Asian and 3.7% from
Subsaharian regions. The subgroup of southamerican patients and those
from Western-origin presented similar rates of BPD diagnosis to those
from the native sample. Asian and Subsaharian subgroups presented
lower rates of BPD diagnosis than native group.
Conclusion: These results indicate differences in the BPD diagnosis
according on the region of origin. Cultural differences between subgroups and level of cultural integration could explain some results.
References: 1.-Baleydier B, Damsa C, Schutzbach C, Stauffer O, Glauser D.
Comparison between Swiss and foreign patients characteristics at the
psychiatric emergencies department and the predictive factors of their
management strategies. Encephale 2003;29:205-12. 2.-Perez-Rodriguez
MM, Baca-Garcia E, Quintero-Gutierrez FJ et al. Demand for psychiatric
emergency services and immigration. Findings in a Spanish hospital during the year 2003. Eur J Public Health 2006 8.
P-20-03
Attention Deficit Hyperactivity Disorder (ADHD) and narcissistic personality: A relationship?
Mario Louza
Introduction: Recent studies of narcissism suggest the usefulness of differentiating between two ways (overt and covert) in which the underlying narcissistic personality is expressed in current behavior. Overtly and
covertly narcissistic individuals share characteristics such as self-absorption, feeling of being special, and a basic vulnerability to slight. Overt narcissism shows sense of social poise, extraversion, and rebelliousness that
is reflected in the DSM-IV criteria for Narcissistic Personality Disorder
(NPD). Among covert narcissism an underlying inflated sense of the self is
frequently obscured by an introverted interpersonal style, feelings of
depression, anxiety, an absence of zest for work and a sense of insecurity
and vulnerability (Wink,1991). Studies have previously reported substantial overlap between NPD (overt narcissism) and Borderline Personality
Disorder (BPD) -affect dysregulation, impulsivity, unstable relationships
(Kernberg, 1975). Other studies reported relationship between BPD and
Attention-Deficit Hyperactivity Disorder (impulsivity, mood lability, feelings
of boredom). Differences are that BPD patients have suicidal preoccupations, continued self-mutilation and fear of being abandoned (Wender,
1998). We did not find in the literature any research that associating
ADHD with the two forms of narcissism (covert/overt). Our purpose is to
investigate, through a systematic bibliographic research, the possibility of
overlap between narcissistic personality and ADHD.
Method: Bibliographical research was completed using Lillacs and
Pubmed from 1975 to 2006.
Results: We observed notable phenomenological similarities between
narcissistic personality and ADHD in adults: anger to criticism, tendency
to withdraw into fantasy, difficulty in executate plans, intense feelings of
insecurity and inadequacy, self-absorption, resentment of authority, lack
of empathy, antisocial behavior, novelty seeking, substance abuse, affect
dysregulation, impulsivity, and unstable relationships. The symptoms
manifest chronically and there are evidences of heritability (Heiser, 2006;
Torgersen, 2000).
Conclusion: There is a possible overlap between ADHD and narcissistic
personality and more studies are needed in order to clarify this hypothesis.
References: 1. Wink, P. Two faces of narcissism. Journal of Personality
and Social Psychology. 1991;61,590?597. 2. Kernberg, O.Borderline conditions and pathological narcissism. New York: Jason Aronson;1975. 3.
Wender, P.H. Attention Deficit Hyperactivity Disorder in adults. Psychiatric
Clinics of North America. 1998;21(4):761-774. 4. Heiser, P.Twin study on
heritability of activity, attention, and impulsivity as assessed by objective
measures. J Atten Disord. 2006;9(4): 575-581. 5. Torgersen, S. A twin
study of personality disorders. Comprehensive Psychiatry.
2000;41(6):416-425.
213
OTHER - Poster
P-20-04
Panic disorders in adult celiac disease
Svetlana Kopishinskaya
Nizhny Novgorod Med. Acad., Chair of Neurology + Psych., Russia
Alexander Gustov
Introduction: Celiac disease is an autoimmune gastrointestinal disorder
characterized by mucosal atrophy of the jejunum on exposure to gluten,
a protein found in grains. An increased prevalence of celiac disease has
been reported in psychic symptoms and depression. We planned to evaluate the association between celiac disease and panic disorders and what
part autoimmune impairment of thyroid may play in it.
Method: We revealed 28 celiac patients with panic disorders, 21 females
and 6 males, aged 16-61. The diagnosis of celiac disease was made on
the basis of clinical history, serological criteria and endoscopical duodenal
biopsy. Panic disorder was formulated using the International Composite
Diagnostic Interview, according to DSM-IV criteria. Thyroid was evaluated
with palpation, echography and measurement of serum-free thyroid hormones (FT4, FT3), thyroid-stimulating hormone (TSH) and antithyroid
autoantibodies (anti-TPO). Celiac patients were evaluated for the level of
knowledge about celiac disease and the compliance with gluten-free diet.
Results: Anti-TPO were significantly high in 17 celiac patients. In
22 patients, the panic disorders improved quickly with a gluten-free diet.
Conclusion: In conclusion, we think celiac disease should be taken into
consideration in the presence of panic disorders, particularly if they are
not responsive to psychopharmacological therapy, because withdrawal of
gluten from the diet usually results in disappearance of symptoms.
Screening for celiac disease in all cases of panic disorders with subclinical
thyroid disease is therefore recommended.
P-20-05
Oxytocin plasma levels and romantic attachment
Donatella Marazziti
University of Pisa, Psychiatry, Italy
Stefano Baroni, Michela Picchietti, Mario Catena, Marina Carlini, Gino
Giannaccini, Antonio Lucacchini, Giovanni Ciampa, Liliana DellOsso
Introduction: Recent data would suggest that oxytocin is one of the
mediators of important processes that are fundamental for the survival of
the species, such as the initiation and maintenance of infant attachment,
maternal behaviour and pair-bonding. In the present study we aimed to
explore the possible relationships between plasma oxytocin levels and
romantic attachment in a group of healthy subjects.
Method: Forty-five healthy subjects (12 male, 33 female, mean age 31.5
6.2 years) with no family or personal history of any major psychiatric
disorder were enrolled in the study. All subjects were free of physical illness, were neither heavy cigarette smokers, nor did any take regular medication. Thirty-three subjects had a current romantic relationship with a
mean duration of 80.5 months (ranging from a minimum of one month
to a maximum of 25 years); the remaining 12 had no current relationship.
The romantic attachment was assessed using the Italian version of the
Experiences in Close Relationships (ECR), a self-report questionnaire for
measuring this parameter in adults.
Results: Plasma oxytocin levels were unrelated with age, gender, marital
status, or length of the relationship and ranged between 0.13 and
4.59 pg/ml (mean+SD: 1.53+1.18). A significant and positive correlation
was observed between the anxiety scale of the ECR and oxytocin levels
(r= 0.30, p= 0.04). On the other hand, the correlation between the avoidance scale and oxytocin levels was not significant (r= 0.12, p=0.42). The
distribution of attachment styles was twenty-six (57.8 %) subjects
showed a secure attachment, 12 (26.7 %) a preoccupied, 5 (11.1 %) a
fearful/avoidant and 2 (4.4 %) a dismissing style. Although no statistical
correlation was observed between these styles and oxytocin levels, the
preoccupied style of attachment was related to higher peptide concentrations.
Conclusion: Anxiety and oxytocin seem to be positively linked in romantic
attachment: that is, the higher or lower the oxytocin levels, the higher or
lower the score on the anxiety scale of the ECR. It could be speculated
that this link represents the biological basis of those processes resulting in
positive emotions related to romantic attachment and, possibly, to all
social bondings.
214
References: Aron A, Fisher H, Mashek DJ, Strong G, Li H, Brown LL 2005

Reward, motivation, and emotion systems associated with early-stage
intense romantic love. J Neurophysiol 94(1), 327-37
P-20-06
Validation of a new motor subtype scheme for delirium
David Meagher
St Annes Day Hospital, Psychiatry, Limerick, Ireland
Maeve Leonard, Paula Trzepacz
Introduction: We sought to validate a new approach to motor subtyping based on analysis of data from a controlled comparison of items from
three existing psychomotor schema to identify a subgroup of items that
correlated substantially with an independent severity rating of motor
presentation and were relatively specific for delirium.
Method: Consecutive cases (n=100) of DSM IV delirium identified in a
palliative care setting were assessed by a research physician using the
Delirium Rating Scale-Revised-98 (DRS-R98) and the Cognitive Test for
Delirium (CTD). Motor symptoms were rated by nurses using the Delirium
Motor Checklist (DMC). The DMC consists of 30 nonredundant items
from among three previously published psychomotor subtyping schema.
Nondelirious controls (n=52) in the same setting were compared on DMC
ratings. 24 hour Accelerometry (motion analysis) was used to explore differences between subtypes.
Results: Principal components analysis of the DMC identified nine factors. Only two factors correlated significantly with either the DRS-R98
motor agitation (#7) or retardation (# 8) items. Symptoms loading at
> 0.65 were extracted to form subtype criteria composed of 4 hyperactive items and 7 hypoactive items. Application of these criteria to the
delirious population suggested a cutoff of 2 items for subtypes with
30 hypoactive, 28 hyperactive, 27 mixed, and 15 no motor subtype
patients. Patients who did not meet criteria for a motor subtype had less
severe delirium as measured by the DRS-R98 and CTD. Subtypes substantially differed in relation to overall volume of movement as well as number
of changes in posture.
Conclusion: We validated a new scale for rating motor subtypes in delirium that, while derived from existing approaches, is more concise,
focused on motor disturbances, and validated against nondelirious controls and independent rating of pure motor disturbance by the DRS-R98
and accelerometry readings.
References: Meagher DJ, Trzepacz PT (2000). Motor subtypes of delirium. Sem Clin Neuropsychiatry 5:75-85. Trzepacz PT, Meagher DJ (2004).
Delirium. American Psychiatric Association Textbook of ConsultationLiaison Psychiatry. American Psychiatric Association, Washington, USA
P-20-07
Lamotrigin in the epilepsy therapy at the Sarajevo
Neurology Clinic
Azra Alajbegovic
Clinical Center, Neurology Clinic, Sarajevo, Bosnia and Herzegovina
S. Alajbegovic, E. Suljic, A. Kulenovic-Dzubur, A. Bravo-Mehmedbasic, A.
Kucukalic
Introduction: New antiepileptic drugs have opened a new era of therapy
in the epilepsy treatment. The aim of this paper is to establish a therapeutic effect of the new antiepileptics (AE) as a supplement therapy in the
treatment of those types of epilepsy which proved to be resistant to previously used therapy, with a special emphasis on lamotrigin.
Method: The research was undertaken at the Sarajevo Neurology Clinic.
It comprised 60 epileptic patients (30 patients with the old antiepileptic
therapy, 30 with the new antiepileptics as add on). All patients had partial epileptic fits with secondary generalizations.
Results: The male female ratio in both groups was the same 16M:14F.
33% of patients were under 20, mean age was 27.2 years. The most frequent antiepileptic therapy was the combination of carbamazepin and
lamotrigin in 67% of patients in the group with the new AE, while 90%
of patients in the group with the old AE received carbamazepin.
Conclusion: New antiepileptics have proven to be efficient as a supplement therapy in the treatment of previously resistant epileptic fits. The
frequency of fits was reduced in 66.7% of patients, and in 16.7% of
OTHER - Poster
patients the fits were alleviated. The new AE did not significantly influence the psychological traits of patients; in all patients an improved quality of life was noted after introducing the new lamotrigin to the therapy.
P-20-08
Malondialdehyde levels in adult attention deficit/hyperactivity disorder
Haluk Savas
Gaziantep Universitesi, Psikiyatri AD, Turkey
Mahmut Bulut, Salih Selek, H. Serdar Gergerlioglu, H. Ramazan Yilmaz,
Murat Yuce, Giyasettin Ekici
Introduction: Recent evidence supports 4 % prevalence rate of adult
attention deficit hyperactivity disorder (A-ADHD) (1). Malondialdehyde
(MDA) is the breakdown product of the major chain reactions leading to
oxidation of polyunsaturated fatty acids and thus serves as a reliable
marker of oxidative stress (2). Recent studies reported elevated MDA
activity in various psychiatric diseases (3) as well. In the present study, we
aimed to examine the association between MDA and A-ADHD.
Method: 20 A-ADHD patients diagnosed according to The Turkish version of Adult ADD/ADHD DSM IV- Based Diagnostic Screening and Rating
Scale and 21 healthy volunteer controls were included to the study(4).
The serum MDA levels were determined by the method of Draper and
Hadley (5).
Results: The mean serum MDA level in patients with A-ADHD (2.44
0.84 nmol/ml) was higher than those of the controls (0.360.20
nmol/ml) (t= 11.01, df= 39, p< 0.05). MDA levels were correlated with
hyperactivity fulfilled number of criteria (n= 20, p= 0.01, Ro= 0.56) and
total score in hyperactivity/impulsivity subtitle (n= 20, p= 0.02, Ro= 0.51).
Conclusion: This is the first study evaluating the oxidative metabolism in
A-ADHD. The present study shows that the mean serum MDA levels of
patients A-ADHD were significantly higher than control group. As in other
psychiatric disorders, higher MDAs may play a role in the pathophysiology of A-ADHD. In our study MDA levels were correlated with hyperactivity fulfilled number of criteria and total score in hyperactivity/ impulsivity
subtitle. Recent studies demonstrated evidence of increased oxidative
breakdown of fatty acids which leads to low levels of omega-3 compounds in the cell membrane of ADHD subjects (6). Some studies have
also shown that of fatty acid deficiency were significantly associated with
the severity of reported behavior problems (7). Our present study has
shown that the increase of lipid peroxidation in A-ADHD patients and this
might be the reason of fatty acid deficiency in ADHD subjects. In our
study MDA levels were correlated with hyperactivity fulfilled number of
criteria and total score in hyperactivity/impulsivity subtitle in A-ADHD subjects. Thus there may be an association between reliable measures of
MDA levels and particular clinical symptoms and aspects of hyperactivity
behavior. Our results suggest that A-ADHD may be associated with fatty
acid oxidation, a finding which may bear further treatment designs. MDA
may predict hyperactivity among subjects.
P-20-09
Level of the contents magnesium and some mineral substances in blood of the patients with obsessive - compulsive disorders
Marat Assimov
Guram Pichkhadze, Anastasiya Kurbanova
Introduction: The interrelation between a level of the contents of mineral substances and weight by display at the patients OCD for revealing
role magnesium and other mineral substances in development of the
given pathology is investigated.
Method: In job for research 27 out-patient patients with various weight
of display of symptoms of illness, from them 22 women and 5 men in the
age of from 20 till 80 years undertook. The control was served by the
healthy persons about similar of age (of a floor) - 12 men. The contents
of mineral substances in blood healthy and patients of the persons determined with the help of the semi-automatic biochemical analyzer (Screen
Master).
Results: The researches have shown that the contents of mineral substances in blood of the patients OCD considerably differs from healthy.
And, the contents last in blood of the patients appreciably depend on
weight of display of illness.
Conclusion: The received preliminary results testify to role magnesium in
pathology of development OCD that requires the further research.
P-20-10
How comorbid body dismorphic disorder can modify clinical
features and psychiatric comorbidities in obsessive-compulsive disorder patients
Ygor Ferrao
Centro Univ Metodista IPA, Post-Graduation, Porto Alegre, Brazil
Luciano Guterres, Maria Alice de Mathis, Ana Cristina Nakata, Juliana
Diniz, Albina Torres, Euripedes Miguel
Introduction: Obsessive-compulsive disorder (OCD) is an heterogenous
disorder. If it centers the Obsessive-compulsive Spectrum it may share
some features with other disorders, where one of them is Body
Dismorphic Disorder (BDD). We intended to verify how BDD may interfere
with clinical presentation and psychiatric comorbidities of OCD patients.
Method: This cross-sectional study compared 282 OCD patients with
48 OCD+BDD patients, focusing on some intrinsic and some extrinsic clinical characteristics.
Results: At the logistic regression model, OCD + BDD group more frequently showed social phobia, skin picking, and Tourette Syndrome. The
severity of anxiety and depression according to Beck scales were higher
for OCD + BDD group, that also presented more frequently somatic
obsessions and compulsions of ordering and hoarding. YBOCS did not
showed differences between groups.
Conclusion: BDD associated to OCD may alter the clinical presentation of
the disorder, stressing the heterogenous presentation of OCD.
References: 1- Philips,K et al. OCD versus BDD: a comparision study of
two possible related disorder. Depression and Anxiety, 2006. 2- Frare E et
al. OCD and BDD: a comparision of clinical features. Eur. Psychiatry, 2004.
P-20-11
Intrinsic obsessive-compulsive disorder phenomena and
temperament and character features in obsessive-compulsive patients
Ygor Ferrao
Centro Univ. Metodista IPA, Post-Graduation, Porto Alegre, Brazil
Helena Bins, Maria Eugenia de Mathis, Maria Conceicao do Rosario,
Hermano Tavares, Euripedes Miguel
Introduction: Obsessive-Compulsive Disorder (OCD), as a heterogeneous
disease, may influence individual personality features. Dimensional strategies may help to identify more homogeneous groups of OCD.
Method: This cross-sectional study intended to evaluate how intrinsic
OCD phenomena could influence on aspects of temperament and character. Temperament and Character Inventory and Dimensional YaleBrown Obsessive-Compulsive Scale were applied to 50 OCD patients
diagnosed according to DSM-IV.
Results: Patients with aggressive and sexual/religious obsessive-compulsive dimensions showed higher scores on persistence; simetry/order
showed higher scores on harm avoidance and lower on self-directness
and cooperativeness; contamination/washing showed higher scores on
harm avoidance. The sample also showed that as higher the scores of
DYBOCS, lower the scores on self-directness. Anxiety and depression may
be confounding variables on novelty seeking, harm avoidance and selfdirectness.
Conclusion: Obsessive-compulsive symptoms content, the intensity of
OCD and of the anxiety and depressive symptoms seems to have some
influence on temperament and character of OCD patients. Prospective
studies on temperament and character of OCD patients, with response to
treatment evaluation, may be conducted.
References: 1- Cruz-Fuentes et al. Severity of Obsessive-Compulsive
symptoms is related to self-directedness character trait in ObsessiveCompulsive Disorder. CNS Spectrum, 2004:9(8):607-12. 2- Clonninger, R.
A practical way to diagnosis personality disorder: aproposal. J Pers Dis,
215
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2000:14(2):99-108. 3- Rosrio-Campos et al. The dimensional Yale Brown Obsessive-Compulsive Scale (DYBOCS): an instrument for assessing obsessive-compulisve symptoms dimensions. Molecular Psychiatry,
2006: 11(5):495-504.
P-20-12
The psychobiology of task completion: Nest building
behaviour as a possible model for understanding the
pathophysiology of obsessive compulsive disorder (OCD)
Kurt Hoffman
Univ. Autonoma Tlaxcala, CIRA, Mexico
Introduction: An understanding of neural mechanisms underlying the
perception of task completion, and the subsequent inhibition of goaldirected behavior, could provide an improved understanding of the
pathophysiology of OCD. The pregnant female laboratory rabbit constructs a nest by repeatedly collecting straw in her mouth and carrying it
into a wooden nest box inside her cage (straw carrying). I am studying
this behavioral pattern, with the goal of defining neural mechanisms
underlying the perception of a completed nest and the subsequent inhibition of further nest building behavior.
Method: Female rabbits (4 d pre-partum) were given straw and their
behavior was observed for 3 hr while they were subjected to the following treatments: 1) allowed to construct their nest normally (control); 2)
prevented from completing their nest by removing the straw from the
nest box after she deposited it inside; 3) provided with a nest box that
already contained a completed nest. At 3 hr, all straw was removed from
the nest box and weighed, and the empty nest box was returned to the
cage. More straw was placed inside the cage, and at 24 hr the straw
inside the nest box was again weighed.
Results: Placing straw inside the cage stimulated straw carrying in most
females within 15 min. At 3 hr, the females that were provided with a
pre-made nest had carried significantly less straw into their nest box compared to the other 2 groups. However, during the subsequent 21 hr, the
females that had been prevented from completing their nest continued to
carry straw into their nest box, while straw carrying was inhibited in the
control group and in the group that had been given a pre-made nest.
Conclusion: These results indicate that the perception of straw stimulates
the onset of straw carrying behavior in pre-partum female rabbits. The
perception of a completed nest terminates and subsequently inhibits this
behavior for at least 21 hr. An understanding of neural mechanisms
underlying the perception of task completion and the subsequent inhibition of the corresponding goal-directed behavior could provide insight
into the pathophysiology of OCD, in which both of these processes are
dysregulated.
P-30
Other IV
T12 Other
P-30-01
Clinical features and main causes of ospitalisation in
repeat users of psychiatric emergency service in a general
hospital
Erika Quintanilla
Universidad de Chile, Residente de Psquiatria, Santiago, Chile
Fanny Layton, Carlos Barrantes, Juan Pablo Osorio, Marcela Rojas, Jorge
Monardes
Introduction: Determine the percentage of repeat users of psychiatric
emergency service in a general hospital. Compare the distribution of
pathologies (ICD-10) and percentage of ospitalisation of this population
in three consecutives years.
Method: It was made a descriptive study of transversal cut. The information was obtained through the medical registry of the Psychiatric Urgency
Service of BLH and the discharge registry from the Hospitalization Unit
between 2003 and 2005.A repeat user was defined as patients who
216
made at least 3 consult in one year. The diagnosis was made according to
ICD-10. Statistical analysis was made with Microsoft Excel and Stata 8.0.
Results: The number of psychiatrist users from 2003 to 2005 were
8053,8735 and 7687, each year. The predominant disorders among all
psychiatric users were in women the mood and neurotic disorders, and
among men were disorders due to psychoactive substance use.
The percentage of consults to repeated users was 16.84%, 16.53% and
14.99% respectively. The principal causes were Schizophrenia,
Schizotypal and delusional disorders, Mental and behavioural disorders
due to psychoactive substance use, Neurotic disorders and Mood disorders. From the total of repeated users, 32% were ospitalisat in 2003,
26.1% in 2004, and 27.9% in 2005. The principal causes of ospitalisation were Schizophrenia and Schizotypal and delusional disorders, being
Mood disorders and disorders due to psychoactive substance use the
second and third mayor cause.
Conclusion: On the period observed in the Urgency Service of BLH the
percentage of repeated users did not differ to the reported in other
Psychiatrist Urgency Services. On the other hand the causes of consultation of repeated users differ from the non repeated users, where the
principal cause was Neurotic disorders.
It is of interest that the mean cause of seeking attention and ospitalisation
among repeated users was Schizophrenia, being most of the patients
decompensate. This observation makes us to reflect about the importance
of the efficiency of welfare network on psychiatrist and mental health.
P-30-02
Download of Psychiatry - a free student text
Saxby Pridmore
University of Tasmania, RHH, Dept. of Psychiatry, Hobart, Australia
Introduction: Medical textbooks are expensive and rapidly outdated.
Student psychiatry texts are not readily available to some students. The
aim was to write a psychiatric text in English at about medical student
level to be placed on the web, where it would be freely available to all
students (teachers and the general public). This text would be updated
regularly. It would be easy to read. It would be interesting, and include
pictures and case histories
Method: A 30 chapter, 350 page document, Download of Psychiatry
(DOP) was written. It was placed on the University of Tasmania webpage
on July 28, 2006. It is available via Google, or the link: http://
eprints.comp.utas.edu.au:81/archive/00000287/. Notice of the availability
of DOP was emailed to all known medical schools, many nursing, social
work and some psychology schools.
Results: 1. In the first 10 weeks, 12 500 chapters were downloaded.
2. Downloads went to the following countries : Australia, 42%; USA,
40%; New Zealand, 5%; South Africa, 4%; United Kingdom, 3%,
Canada, 2%, China, 2%, Hong Kong, 1%. The rest of the world accessed
less than 3% of the total.
Conclusion: It is possible to create a free psychiatry text in English which
is consulted by students. However, the uptake is skewed to those countries with advanced technology in which English is widely spoken. It may
be possible to reduce reliance on technology by distributing the text on
CD (which would over come the need for internet connection). It may be
possible to reduce the language problem by having the text translated
into other languages.
References: http://eprints.comp.utas.edu.au:81/archive/00000287/
P-30-03
Neurosyphilis revisited - a challenging case report with
psychiatric manifestations
Margarida Lobo
Hospital N. Senhora do Rosario, Psychiatry, Barreiro, Portugal
Susana Fernandes, Susana Mendes, Zaida Pires, Antnio Paiva, Julieta
Chainho, Jos Graa, Manuela Pereira
Introduction: The incidence of neurosyphilis, the infection of the central
nervous system by the spirochete Treponema pallidum, is rising in spite of
widely available curative treatment. The authors present a case of a
43-year-old patient that showed a multitude of psychiatric signs and
symptoms - personality changes, bizarre behaviour, verbal aggressions,
OTHER - Poster
agitation, insomnia, auditory hallucinations, persecutory and megalomania delusions, spatial and temporal disorientation, leading to a direct
admission to a psychiatric unit.
Method: Literature review derived from the MEDLINE and PUBMED database.
Results: This disease may present as virtually any psychiatric disorder,
including personality disorder, depression, mania, psychosis, delirium and
dementia. The authors suggest criteria for screening and stress that a specific treponemal test should be used because of their higher sensitivity.
Treatment should consist of penicillin plus psychotropics for any psychiatric symptoms secondary to or concurrent with neurosyphilis.
Conclusion: The authors recommend that clinicians have a high index of
suspicion of neurosyphilis, which may have an exclusively psychiatric presentation rather than medical or neurological symptoms.
References: Sobhan, T. (2004), Three Cases of psychiatric Manifestations
of Neurosyphilis, Psychiatric Services, 55:830-832; Brown, D. (2003),
Diagnosis and Management of Neurosyphilis, Am Fam Physician, 68:28390.; Gastal, F. (1999), Tratamento Etiolgico em Neurosfilis: o modelo da
neurosfilis, Rev Bras Psiquiatr, 21(1), Ritchie, M (1998), Neurosyphilis:
Considerations for a Psychiatrist, Priory Lodge Education.
P-30-04
Assessing the new graduate, physician, job stressful factors
during transition period in teaching centers and affiliated
hospital of Ardabil, Medical Sciences University, 2005-2006
Zahra Tazakori
Ardabil, Iran
Z. Hashempour, P. Molavi
Introduction: In process of transition or transfer from student role to
qualified physician in the medical university is one of the high lighted
stressful periods. Pressure of work, especially in terms of medical education that student have preparing for beginning the work & doing professional knowledge & skills were have the most stressful. In the other manner, the impending graduation and the transition to increased levels of
responsibility were high lighted as particular stressful periods. Medical
student have passed many of transition periods in there graduation time.
Transition between physiopathology and preclinical, preclinical and clinical training , and clinical training to beginning work. Most of new graduate physician because of exposure to new and unknown situation and
position be involved in stress at the six month of beginning the work. A
perceived lack of support from the medical school and responsible also
appeared to add the new graduates physician stress level. Therefore it is
necessary to recognize effects of transition process on the new graduate
physician and the stressful job experiences in the transition period from
student role to employment to decrease new graduates stress.
Method: This survey is a descriptive study in which job stress full factors
of new graduate physician during transition period has been assessed the
date were collected by using a questionnaire including 4 section. Target
population consisted of all of new graduates placed at the end of first six
month of work, the sample size was as population and consists of 62
peoples and census was used in sampling method. Data analysis was
done using descriptive statistic (frequency, percent, mean, and std-error).
Results: The finding of this study indicated that many of new graduate
physician in the transit period had undesirable supportive stressful factors
(61.2%) as well, high level of individual(58%) and caring stressful factors(53.2%). From the supportive stressful factors paint of view, not
implementation of orientation programs in the first job from the responsible with (14.5%) and the chance of partnership in the determines from
the responsible with (29 %) were the least of supportive stressful factors.
From the individual stressful factors need to new skills with (40.3%),
exposure to the new situation & position and responsibilities with
(22.6%) reported as the most stressful factors. From the caring Stressful
factors, caring the patients in the critical position and during patients with
(29%) and awarding the patients and their family with (22.6%) were the
most important caring stressful factors. Also in spite of the most of physician (54.8%) had a little management stressful factors , the heavy bulk of
work with(51.6%) and incongruity between condition of work setting
and what learned in education course with(22.6%) identified as highest
stressful events.
Conclusion: The finding of this study indicated that supportive , individual & management factors was the stressful factors of new graduates
physician in the first six month of work. Therefore explaining and orientation the new educate physician with real situations of work setting is
necessary.
P-30-05
Mental health research capacity in Latin America and the
Caribbean: Focus on basic sciences
Carla Gallo
Universidad Cayetano Heredia, Lab Investigacion y Desarrollo, Lima, Peru
Fabian Fiestas, Giovanni Poletti, Denise Razzouk, Jair Mari, Ines
Bustamante, Silvana Sarabia, Abel Sagastegui, Guido Mazzotti
Introduction: Basic sciences (BSci) - along with epidemiological and clinical research- are a key element in efforts to improve mental health conditions across the world. This study aims to evaluate the BSci research
capacity for mental health and related disciplines, currently existing in
Latin American and the Caribbean (LAC) countries. This is part of a larger
initiative of the Global Forum for Health Research aimed at mapping a
roster of actors and research agendas in low- and middle income countries, traditionally unable to efficiently respond to health challenges with
local research data based- policies and interventions
Method: A questionnaire/survey was sent to 2664 researchers and stakeholders identified by a mapping process through publication databases
(1993-2003), internet searches of institutions, and snowball sampling.
We received response of 463 researchers and 119 stakeholders, from
15 of 30 countries in the region.
Results: Two hundred sixty-two out of 2653 PsycInfo or PubMed indexed
mental health publications were related to BSci. Only 9 LAC countries had
mental health publications in this area. One out of four researchers in
mental health in the region mostly psychiatrists (54%) and neurologists
(14%) - had formal training in BSci research methods. About 40% of
them declared to have technical support in neurosciences and/or BSci
research in their institutions. Barely 10% of the research projects in the
past 5 years had a BSci approach. Most (45%) were local, but 35% were
done in collaboration with developed countries, being funded mainly by
NGOs or foundations (28%). The main motivations for research in BSci
were personal interest (28%), and burden of disease (26%). BSci research
was not considered a priority by most (60%) researchers or stakeholders.
Conclusion: BSci research in mental health is not a priority in the region.
There is a need to redefine the role of BSci in mental health research,
establishing agendas and setting priorities based on local necessities.
References: 1. World Health Organization. Mental Health Atlas 2005.
WHO, 2005. 2. Global Forum for Health Research. Ivo Nuyens. No
Development without Research. 2005. 3. Zenteno-Savin T, Oliveira R,
Hermes-Lima M. The cost of Latin American science Introduction for the
second issue of CBP-Latin America. Comparative Biochemistry and
Physiology, Part A (2006). In Press. 4. Global Forum Update in Research
for Health 2005. 5. Promoting Mental Health: Concepts, Emerging
Evidence, Practice : Report of the World Health Organization, / [editors: H
Herrman, S Saxena, R Moodie]. WHO 2005.
P-30-06
Latin-American psychiatrist profile
Rodrigo Nel Crdoba
CISNE, Psychiatry, Bogot D.C., Colombia
Ismael Salazar, Juan Fernando Cano, Ricardo Cendales, Marcela Alzate,
Ana Olarte, Liliana Gonzalez, Claudia Vanegas
Introduction: The Professionals in charge of mental health are identified
as a high risk group in terms of laboral stress, Chronic Fatigue Syndrome,
and psychiatric disorders. The psychiatrists Professional satisfaction can
influence the quality of the psychiatric services. Objective: To describe the
professional satisfaction of the psychiatrist affiliated to the Psychiatric
National Societies in 19 Latin-American countries (Argentina, Bolivia,
Brasil, Colombia, Costa Rica, Cuba, Republica Dominicana, Ecuador,
Chile, El Salvador, Guatemala, Honduras, Mexico, Nicaragua, Peru,
Panama, Paraguay, Uruguay, Venezuela).
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OTHER - Poster
Method: A probabilistic sample (Stratificated random sample) of the

associated psychiatrists in every one of the 19 participants countries; To
the psychiatrist selected in the sample was requested to fill up an electronic questionnaire which look-for some aspects related with personal
and laboral issues.
Results: In the eleven countries with answers rate above 70%, 887 psychiatrist were polled; in the others countries 405 psychiatrist were polled.
the average age was 48,2 years; the average experience was 18,2 years,
63,8% were male and 97,4% of the polled were exercising its practice at
present. Most of polled declared themselves satisfied with their quality of
life level (70,8%), a slight bigger percentaje declared themselves satisfied
with the daily task of the psychiatrist practice (86,4%); nevertheless,
35,3% declared being not satisfied with the incomes obtained from its
practice.
Conclusion: The factors which associated more with dissatisfaction in the
psychiatrists quality of life were: The sensation of shortage of the incomes
obtained from its practice in order to satisfy their needs (OR 8,2), to have
an income below two thousand dollars (O.R. 2,26), to have short holidays
period, to have prolonged working days, and attending a high number of
patients in a daily working day.
References: Haas JS. Physician discontent: a barometer of change and
need for intervention. Journal of General Internal Medicine 2001;16:496497. Thomsen S, Soares J, Nolan P, Dallender J, Arnetz B. Feelings of professional fulfilment and exhaustion in mental health personnel: the
importance of organizational and individual factors. Psychotherapy and
Psychosomatics 1999; 68:157164. Looney JG, Harding RK, Blotcky MJ,
Bamhart FD. Psychiatrists transition from training to career: stress and
mastery. Atii J Psychiatry 1980;l37:32-6. Prosser D, Johnson S, Kuipers E,
Szmukler G, Bebbington P, Thomicroft G.Mental health, bumout and
job satisfaction among hospital and comunity-based mental health staff.
Br J Psychiatry 1996; 169:334-7.
P-30-07
Migraine and psychopathology
Kittie Dhoine
Vincent van Gogh Institute, RCG Venray, Netherlands
W. Mulleners, W. M. A. Verhoeven, S. Tuinier
Introduction: Migraine is known for many centuries and can be highly
invalidating. The prevalence of this condition for female and male is estimated to be 15% and 5% respectively. The pathophysiology implies the
so called cortical spreading depression which consists of a wave of neuronal and glial depolarization moving slowly over the cortex. This phenomenon is accompanied by a brief and dramatic increase of regional
cerebral blood perfusion, followed by hypoperfusion. These events lead
to a stimulation of the ipsilateral trigeminal nerve. Substantial evidence
shows an association between migraine and psychopathology, especially
anxiety- and mood disorders, including panic disorder, depressive states
and bipolar affective disorder.
Method: In a first study the prevalence of migraine in psychiatric outpatients was investigated. Migraine was diagnosed according to the guidelines of the International Headache Society. A group of consecutively
recruited outpatients (n=95), 27 (female:8; male:9) who met the diagnostic
criteria was collected.
Results: From the 27 patients who met the criteria for migraine, 16 were
given a diagnosis of a mood disorder and 4 of an anxiety disorder. In the
remaining 7 patients, various psychiatric diagnoses were established.
Conclusion: These findings corroborate the comorbidity of migraine in
psychiatric disorders. Moreover, they stress the importance of complete
neuropsychiatric examination. Finally, the comorbidity of psychiatric disorders and migraine warrants a well tailored pharmacological strategy
because of possible interactions. Subsequently a second study was
designed aimed to investigate both the relevance of a structured collaboration between neurologists and psychiatrists in neurological outpatients
with migraine and the psychiatric comorbidity in patients referred primarely to the neurologist.
218
P-30-08
Liaison psychiatry: Achieving quality through education
Gordana Rubesa
Clinical Hospital Center Rijek, Psychiatry Clinic, Rijeka, Croatia
Helena Svesko-Visentin, Jasna Grkovic, Tamara Tic-Bacic, Sandra
Blazevic-Zelic
Introduction: Interventions in liaison psychiatry are predominantly
patient directed, and also can be directed towards crisis (coping strategies), or situations themselves, and aimed at helping medical staff. Our
intention was the education of medical staff trough experience in Balint
groups and expanding their emotional capacities, performing detection
and improving their conscious and unconscious attitudes towards
patients.
Method: In our research 98 nurses and 317 severely ill patients from four
Clinics in Clinical Hospital Centre Rijeka were included. Experimental
group consisted of nurses with one year experience in Balint
group(N=62), and control group consisted of nurses with no similar experience (N=36). They were all tested before the research, and retested
three months after the termination of one year Balint group. We performed the following tests: Questionnaire of conscious attitudes,
MANSA - Quality of life test, STAI- Spielberg test for anxiety, Semantic differential, Becks depression scale, Coping strategies style questionnaire.
Results: We found statistically relevant changes in attitudes at medical
staff (nurses) included in education and with experience in Balint groups.
We found changes in unconscious attitudes: evaluation (p <0.02) and
potention (p<0.04). We also found lower levels of anxiety (p <0.005) and
depression (p<0.01), and higher satisfaction in quality of life(p<0.009).
Among the nurses from control group we did not find statistically significant differences between first and second testing. Education of nurses
resulted in significant changes in unconscious attitudes towards the
patients: activation ( p<0.001) and potention (p<0.001); and statistically
significant increase in development of emotionally directed coping strategies in stress (p<0.001).
Conclusion: Participation of nurses in Balint groups created significant
changes in understanding severely ill patient. It also increased working
performance in medical staff and their quality of life. Indirectly, it
changed unconscious attitudes in patients towards their illness, and it
also changed their use of coping strategies.
P-30-09
A study on morbidity pattern of patients attending psychitary opd, medical college, Vadodara, India
Mohsin Shaikh
M.s.Univ. Medic. Colleg, Baroda Prevent. & Social Med., Kapadwanj,
India
Dr. Mohsin G. Shaikh, Dr. Jayshree K. Rathod
Introduction: WHO data: On global burden of disease Mental illnesses
accounts for over 15 percent of thetotal burden of disease. Disability
caused by major depression ranked second only to ischemic heart disease
in magnitude of disease burden.INDIA - Urban morbidity is 3.5 % higher
than the Rural India has a high rate of suicides - 89,000 persons committed suicide in 1995, increasing to 96,000 in 1997 and 104,000 in 1998,
which is a 25% increase over the previous year(WHO 2001b). To find out
the common psychiatric disorders among patients attending psychiatry
OPD and also to study the role of factors like age, sex, education and
occupation, marital status and various precipitating factors on mental
health status of the patients. Study Design: Cross Sectional Study.
Methods: A total of 200 patients were studied in a period of two months
(Aug-Sept 05). Patients attending psychiatry OPD were examined with
the help of a trained psychiatrist. Information regarding the patients was
taken using pre-designed structured proforma. Diagnosis was made by
trained psychiatrist based on ICD-10 classification in regard to DSM IV
criteria. Settings: Psychiatry OPD of SSG Hospital, Vadodara.
OTHER - Poster
Results: Majority of psychiatric patients (27.8 %) belonged to age group

20-29 years and above 49 years in 25.5 % cases, most of them were
males (59.9 %). Occupational analysis showed that more number of psychiatric patients (32%) belonged to labourer group followed by unemployed (26%). 39% of patients belonged to class IV, Modified Prasads
Classification and in 12.5 % cases psychiatric problems were precipitated
by poor financial condition. Psychiatric problems were more in illiterates
(28%) and majority of the patients (65.5%) were married. In 46% cases
patients were suffering from various health related problems and 12 %
of patients consumes alcohol. The morbidity pattern showed that majority were affected by depression (29%), schizophrenia (18%) and substance abuse psychiatric disorder (11%).Key words: psychiatric disorder,
OPD, diagnosis
Conclusion: Majority of psychiatric patients belonged to age group
20-29 years and above 49 years, most of them were males.also so many
other factors like marriage, occupation, education and other important
precipatiting factors will play a major role in psychiatric morbidity.
P-30-10
Retrospective revision of consultations to the psichosomatic
service during the year 2005
Antonio Serrano Garcia
Hospital Miguel Servet, Dept. of Psiquiatria, Zaragoza, Spain
Tirso Ventura, Cristina Soler, Mariam El-Khatib
Introduction: In a general hospital there is a big requirement of psychosomatic service, if we want to answer to the requests made by other services is necessary to know why they ask for us and also is necessary to
know how we have answered them until now. This study is a revision of
the year 2005.
Method: We revise the consulting sheets during the year 2005 registering the age and sex of the patient, the service that ask for us, the priority
of the consultation, the principal diagnosis and the secondary one if it
exists, the treatment and the derivation after non-psychiatric cares.
Results: During the year 2005 the Psychosomatics service attended
846 patients, aged between 16 and 94 years old. 53,66% were male and
46,34% female. The priority was normal in 343 cases, in the day in
425 cases and urgent in 78. The most common diagnosis group was
F4 with 241 cases, also common were the F3 with 198 and F0 with 170.
In 95 cases a secondary diagnosis was made, in 52 cases there was no
diagnosis and in 21 cases it was not registered. The pharmacological
group more often used was the antidepressants (n=322), also were common the benzodiacepines and hypnotics (n=152) and the antipsychotics
(n=150). In 91 cases drugs were not required. The more usual complementary treatment was benzodiacepines and hypnotics. In 98 cases the
treatment was not registered. After medical restoration 624 patients were
remitted to his primary care doctor, 202 were sent to his reference psychiatry and in 14 cases the patients were hospitalized in our short stance
psychiatric unit. In three cases derivation was not registered and three
patients died before psychiatric interview.
References: 1.- Krautgartner M et al. Need and utilization of psychiatric
consultation services among general hospital inpatients. Social Psychiatry
and Psychiatric Epidemiology. Apr 2006. Vol 41, Iss 4; pg 294.
2.- Bourgeois J; Wegelin J; Servis M; Hales R. Psychiatric Diagnoses of 901
Inpatients Seen by Consultation-Liaison Psychiatrists at an Academic
Medical Center in a Managed Care Environment. Psychosomatics. Jan/Feb
2005; 46, 1; pg 47.
P-30-11
Brief neuropsychological battery (BNB) to detect presence
of cognitive impairment (CI) in patients who maintain
driving habits
Daniel Raul Zuin
FUN CER MEN, Mendoza, Argentina
Luciano Recchia, Andres Barboza
Introduction: Traffic accidents are one of the main causes of mortality.
The increase in life expectancy of general population leads to a raise in
the prevalence of CI. That is why implementing brief and simple diagnostic tests is relevant in detecting subjects with dementia (D); since its presence implies an increase in the prevalence of risky driving habits and/or
car accidents. Objectives: To determine specificity (E), sensitivity (S), predictive positive and negative values (PV+ and PV-) of a BNB to detect
patients who suffer CI in a group of individuals who keep driving habits.
Method: In a total of 215 patients who had consulted for memory problems, we selected those who were driving at the time of consultation
(n=102), who were put under a semi structural neurological, psychiatric,
clinical and neuropsychological protocol, then a D diagnosis and its type
was made for them according to International Criteria. After BNB (Mini
Mental Test [MMST], abbreviated clock test and semantic verbal fluency
test) utility for deterioration diagnosis in serial form were evaluated; (cut
off were <24, <3 and <13 respectively).
Results: (see table below: diagnostic utility of the BNB in determining the
presence of D) The calculation of probabilities took place after testing
(Bayess Theorem) considering a true D prevalence of 20% (approximate
calculation for a general population among 65-80 years old), its result
was a negative post-test probability of 3.7%
Conclusion: The former BNB has acceptable E and S to detect CI in a
group of people who complaint of memory problems and still maintain
driving habits. Also, the predictive values were adequate. The low proportion of false negatives for this battery in our sample should be emphasized. These values are still lower if they are calculated for the prevalence
of D of 20%. The results previously described convert BNB into an ideal,
valid screening and diagnostic tool for senior patients seeking permission for driving.
219
OTHER - Poster
P-30-12
Neurobiology of ethical behavior: Some comments based
on Francisco Varelas neurophenomenology
Maria Valdivia
Iquique, Chile
Introduction: The purpose of this work is to present a critical analysis of
one aspect of Francisco Varelas work on the study of ethical behavior and
its neurobiological foundations in light of current knowledge on neurocognition. Said author poses basic questions about the way of better
understanding behavior and how this is developed and made manifest in
humans. Psychic phenomenology was one of the main focuses of interest
for this scientist, who fueled a new research paradigm called neurophenomenology in which he tried to conciliate neurobiological research and
oriental philosophies, such as Buddhism and others. Ethical human
behavior is analyzed, posing the problem of how we carry out ethical
actions facing immediate confrontation with perceived facts.
Method: Critical analysis of bibliographic review of related texts.
Results: An approach to understand behavior and how it is acquired.
From Varelas point of view, the proximity between perception and action
exists, opposing the normal approach of examining ethical behavior,
which begins by analyzing the intention of an action and ends evaluating
the rationality of specific moral judgments. A paradigm change is presented, where knowledge units are mainly understood as concrete or corporeal and where the cognitive being behaves structurally linked to the context.
Conclusion: Ethical action begins in immediate confrontation with the
facts that we perceive. It is important not to confuse ethical behavior with
moral judgment, a rational process that is not necessarily linked to behavior. Cognition is based on concrete activities of the organism as a whole,
in the sensor-motor area. Cognitive properties are distant from the artificial intelligence model; the cognitive being is made up of his/her history
and actions. Neuronal networks do not work hierarchically; global effects
are achieved where context matters. We have a disposition for an action
coherent with each specific situation and we constantly move from one
to the next.
References: Varela Francisco, Un Know-How per lEtica, 1ra ed., RomaBari, 1992, Gius Laterza & Figli Spa, (Spanish translation by Javier Ortiz
Garca, La Habilidad tica, Barcelona Spain, Debate, 2002, 143 pp.)
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SATELLITE SYMPOSIA
SA-02
Depression: Mechanisms to Medicine
SA-02-01
Neurotransmitters, pain, and depression
Duncan Mitchell
University of the, Witwatersrand, South Africa
Pain is the most common comorbid physical symptom in depressed
patients and successful treatment of depression in these patients also
relieves the painful physical symptoms. In addition to their effect on
mood, data show antidepressants can relieve pain in patients without
depressive symptoms. It is probable that antidepressants relieve pain
through their effect on monoaminergic neural pathways. A likely mechanism for at least part of their antinociceptive action is an increase in
monoamine activity in the descending neural pathways that regulate
nociceptive input. These descending pathways hyperpolarise both primary afferent fibres, arising from nociceptors, and interneurones in the
ascending nociceptive pathways of the spinal cord. Antidepressants may
also act on catecholaminergic antinociceptive pathways in the brain itself.
Serotonin and norepinephrine reuptake inhibitors (SNRIs) are more effective antinociceptives than selective serotonin reuptake inhibitors (SSRIs).
Antidepressants are the most widely used antinociceptive as first-line
therapy for neuropathic pain in patients with normal mood. Neuropathic
pain does not respond to COX inhibitors (NSAIDs, COX-2 inhibitors,
paracetamol) that are the most-common first-line therapies for hyperalgesic nociceptive pain. In recent years, there has been growing understanding of how antidepressants relieve pain, which is likely to lead to
their increasing use as antinociceptives, especially with the availability of
agents with a more tolerable side-effect profile.
SA-02-02
Depression and Pain: A Common Pathophysiology
Amado Nieto-Caraveo
University of Autonoma de, San Luis Potosi, Mexico
The association between pain and depressive symptoms is clear and it has
been documented by many studies, both in the clinical setting and in the
general population1. Near 70% of patients with depression report some
degree of painful symptoms2. This association implies a worse prognosis
of depressive disease. Taking into account this fact is relevant to get a better treatment in a disorder has shown a lower rate of therapeutic
response that we expected3. The homeostatic model of pain states that
pain is both a sensation and a motivation (such as appetite, itching, thirst,
and temperature), a homeostatic emotion between interoception and
exteroception4. This homeostasis is maintained by regulatory pathways
between brain and spinal cord, with the purpose to achieve a balance
between analgesic and hiperalgesic actions. There are several sites of
action of analgesia. The dorsal horn of the spinal cord is the regulation
site of neural transmission through ascending and descending fibers from
mesencephalic nucleus5. At this place, monoaminergic, gabaergic and
opioid neurons interact between pronociceptive and antinociceptive
actions. Serotoninergic fibers from the raf nucleus have both inhibitory
and facilitatory actions. Noradrenergic descending pathways from locus
ceruleus have analgesic effects by activation of alfa-1 (by way of gabaergic interneuron) and alfa-2 receptors in the Wide Dynamic Range (WDR)
neurons. Animal and human studies have shown that drugs that enhance
noradrenergic and serotoninergic activity have analgesic properties6.
Some antidepressants with dual action on these monoamine systems,
like amytriptiline, venlafaxine and duloxetine, improve acute and chronic
painful conditions (like diabetic neuropathy and fibromyalgia)7.
Duloxetine has a more balanced affinity to SE and NE receptors than venlafaxine and a most secure profile than amitriptiline8. Due to these properties, duloxetine may provide some advantages in the treatment of
depression.
References: 1. Ohayon, M.M., et al. Using chronic pain to predict depressive morbidity in the general population. Arch Gen Psychiatry, 2003.
60(1): p. 39-47. 2. Kroenke, K., et al. Common symptoms in ambulatory
care: incidence, evaluation, therapy, and outcome. Am J Med, 1989.
86(3): p. 262-6. 3. Rush A.J. et al. Acute and Longer-Term Outcomes in
Depressed Outpatients Requiring One or Several Treatment Steps: A

STAR*D Report. Am J Psychiatry 2006; 163:1905-1917. 4. Craig, A.D. A
new view of pain as a homeostatic emotion. Trends Neurosci, 2003.
26(6): p. 303-7. 5. Millan, M.J. Descending control of pain. Prog
Neurobiol, 2002. 66(6): p. 355-474. 6. Bomholt, S.F., et al.
Antinociceptive effects of the antidepressants amitriptyline, duloxetine,
mirtazapine and citalopram in animal models of acute, persistent and
neuropathic pain. Neuropharmacology, 2005. 48(2): p. 252-63. 7.
Sindrup, S.H., et al., Antidepressants in the treatment of neuropathic
pain. Basic Clin Pharmacol Toxicol, 2005. 96(6): p. 399-409. 8. Wong,
D.T., et al. Dual serotonin and noradrenaline uptake inhibitor class of antidepressants potential for greater efficacy or just hype? Prog Drug Res,
2002. 58: p. 169-222.
SA-02-03
Optimizing Sustained Remission
Andrea Marquez Lopez Mato
Institute of Biological, Psychiatry, Argentina
Depression is a common, recurrent, often debilitating and potentially
lethal disorder which needs treatment. Response means 50% improvement on a variety of rating scales. To assess treatment remission not only
response is a goal of therapy, assuring wellness beyond improvement.
Remission means return to full functioning. Recovery is a sustained and
total remission for an extended period of time and an absence of disease
state. Failure to achieve full remission results in many negative consequences including increased risk of relapse (76%) , lifelong recurrent
depression (80%), greater impairment in psychosocial functioning,
increased medical morbidity and mortality, as well as increased rates of
suicide and substance abuse. For depressed patients, the measure of
remission is based on their feeling that they have returned to their normal selves. Our clinical conception of depression must be expanded
beyond the affective realm, with somatic symptoms, such as Painful
Physical Symptoms (PPS), included in the definition. Both support a common pathophysiological neurobiological mechanism. Furthermore, 90%
of residual symptoms are physical, which play an important part in not
being able to return to previous functional level and can cause relapse. It
is important to regularly monitor and treat all emotional, including anxiety, and PPS for full remission to occur.
supported by an unrestricted educational grant from Elli Lilly and
Company/Boehringer Ingelheim
SA-03
In search of superior antidepressants
SA-03-01
The place of SNRIs in treatment of depression
Mike Briley
NeuroBiz Consulting, Castres, France
Introduction: Selective serotonin reuptake inhibitors (SSRI) have proven
to be a considerable improvement over tricyclic antidepressants (TCA) in
terms of side-effects especially anticholinergic and cardiovascular effects.
The SSRIs are not, however, devoid of problems and widespread clinical
use has brought a number of other problems to light some of them quite
serious. In terms of antidepressant efficacy there is a general consensus
that SSRIs are less effective than TCAs especially in more severe depression.
221
SATELLITE SYMPOSIA
Method: A new class of antidepressants, the serotonin and noradrenaline reuptake inhibitors (SNRI), has been developed with the aim of providing potent antidepressant activity combined with improved tolerance.
The SNRI class currently comprises three compounds, venlafaxine, milnacipran and duloxetine, which all block the reuptake of both serotonin
(5-HT) and noradrenaline (NA) but with differing selectivity. Whereas milnacipran blocks 5-HT and NA reuptake with equal affinity, duloxetine has
a 10-fold selectivity for 5-HT and venlafaxine a 30-fold selectivity for 5-HT.
In contrast to TCAs all three SNRIs are devoid of interactions at the postsynaptic receptors responsible for many of the side-effects of the older
drugs. As with other dual acting antidepressants, there is evidence for
each of the SNRIs that they may produce superior antidepressant efficacy,
at least in more severely depressed patients.
Results: The different SNRIs vary in their tolerability at therapeutic doses.
Although no direct comparative data are available, venlafaxine seems to
be the least well-tolerated, with serotonergic adverse effects (nausea, sexual dysfunction and withdrawal problems) as well as cardiovascular
effects, principally hypertension, at high doses. Duloxetine appears to be
better tolerated although problems of hepatotoxicity have led to warnings and limitations on its use by regulatory authorities.
Conclusion: The available data suggest that milnacipran is probably the
best tolerated of the SNRIs. In addition because of its lack of hepatic
metabolism there is no risk of interaction with other drugs metabolised
by the hepatic cytochrome P450 system.
SA-03-02
SNRIs in depression and in chronic pain
Siegfried Kasper
Introduction: The common goal of antidepressant therapy sought by a
depressed patient and his physician is remission from all symptoms and a
return to normal functioning. Remission is increasingly seen as the criterion by which all antidepressants should be judged. Early studies showed
that tricyclic antidepressants (TCA), such as clomipramine, produced
greater rates of remission than selective serotonin reuptake inhibitors
(SSRI), such as paroxetine or citalopram. More recently, evidence has been
published that all three serotonin and noradrenaline reuptake inhibitors
(SNRI) also produce significantly greater rates of remission than the SSRIs
studied.
Method: A symptom which is present in a very large number of
depressed patients is chronic pain, commonly backache or painful joints.
In view of the very high comorbidity of chronic pain and depression, many
experts believe that chronic pain is an integral part of the symptomatology of depression. TCAs are effective in reducing chronic pain whereas,
in general, SSRIs are not helpful. SNRIs have been extensively studied in a
variety of pain syndromes. Venlafaxine, for example, has been shown to
be effective in a number of chronic pain conditions both associated with
depression and independent of it, including peripheral diabetic neuropathy. Duloxetine and milnacipran have also been shown to be active in various chronic pain conditions and duloxetine has been approved by the
FDA for the treatment of peripheral diabetic neuropathy.
Results: Fibromyalgia syndrome is a chronic disease of widespread and
debilitating pain, estimated to affect about 3% of the general population.
It is characterised by both physical and psychiatric symptoms suggesting
that it may result from abnormal pain processing within the central nervous system. Currently there is no approved treatment in any country. Both
duloxetine and milnacipran have been shown in double-blind placebocontrolled trials to be effective in reducing pain and other symptoms of
fibromyalgia.
Conclusion: As indicated above, painful physical symptoms are increasingly being seen as an integral part of the symptomatology of major
depression. It may not be a coincidence that the antidepressant drugs
capable of relieving chronic pain such as TCA and SNRI are those that produce remission in the largest number of patients.
222
SA-03-03
Optimising antidepressant response to SNRIs
Marcio Antonini Bernik
Universidade de Sao Paolo, Psychiatry, Sao Paulo, Brazil
Introduction: As with all antidepressants, some patients respond better
to SNRIs, such as milnacipran, than others. Polymorphism of genes coding for the noradrenaline transporter influence response to milnacipran.
The presence of the T allele of the NET-182C polymorphism is correlated
with a greater response to milnacipran, whereas the A/A genotype of the
NAT G1287A polymorphism is associated with a slower onset of
response.
Method: Dopamine transporter VNTR polymorphisms also influence the
rate of response to antidepressant therapy but this effect has been found
in all classes of antidepressants. Similarly, the G/A genotype polymorphism of BDNF G196A is associated with a better antidepressant response
to milnacipran but also to the SSRI, fluvoxamine. These polymorphisms
would therefore appear to involve common downstream pathways of
antidepressant action rather than pathways specific to certain antidepressants. Tolerability can also be influenced by polymorphic differences.
Serotonin transporter VNTR polymorphism and the serotonin transportergene-linked polymorphic region (HTTLPR) polymorphism influence tolerability of drugs acting primarily through the inhibition of 5-HT reuptake,
such as SSRIs and venlafaxine, which has a 100 fold selectivity for the
serotonin transporter. In contrast, these gene polymorphisms have no
effect on the antidepressant response or tolerability of milnacipran.
Results: Differences in metabolism determined by genetic variables in
CYP2D6 activity are a major determinant of venlafaxine levels to such an
extent that genetically determined decreases in CYP2D6 activity have
been associated with cardiovascular toxicity. Milnacipran, which is not
metabolised by the enzymes of the CYP450 system is not influenced by
polymorphism of these enzymes. Low pretreatment levels of plasma
3-methoxy-4-hydroxyphenylglycol (pMHPG) have also been found to predict a better antidepressant response to milnacipran. In addition, improvement in depressive symptoms over 4 weeks has accompanied by increases
in pMHPG levels.
Conclusion: Taken together these recent results confirm that milnacipran
has a major impact on the noradrenergic system in contrast to SSRIs and
venlafaxine whose main target is the serotonin system. Clearly pharmacogenetic data will soon become a significant factor in the choice of the
most appropriate antidepressant medication for a particular patient.
supported by an unrestricted educational grant from Pierre Fabre
SA-05
Do we need another atypical antipsychotic?
S-05-01
Do we need another atypical antipsychotic?
Siegfried Kasper
Atypical antipsychotics were a great advance in the treatment of schizophrenia. However, thus far, there is no antipsychotic with exceptional efficacy and safety in all patients. The atypical antipsychotics have differing
patterns of treatment-emergent side effects. Clinical skills and knowledge are required to find a suitable option for treatment of individual
patients. Following its suspension in 1998, the safety and efficacy of sertindole has been investigated in several post-marketing studies based in
clinical settings. As well as providing the safety data needed to support
the reintroduction of sertindole, these studies have provided specific
examples demonstrating that certain patients, in particular, may benefit
from a switch from other atypical antipsychotics to sertindole.
Sertindole is an effective atypical antipsychotic agent and, as with all the
medications in this group, it is well tolerated with a lack of extrapyramidal symptom side effects. Its individual and mostly favourable profile of
treatment-emergent effects and safety allows for flexibility in treating
patients since they differ in their response and susceptibility to treatment-
SATELLITE SYMPOSIA
emergent effects. Sedation and anticholinergic effects are particularly

troublesome side effects which may be common to some of the atypical
antipsychotics. Sedation may lead to non-compliance during the initial
period of treatment. Sedation may also have consequences for patients'
quality-of-life. Anticholinergic effects may adversely influence cognitive
performance, and they pose a number of risks especially for older
patients. The propensity of sertindole to cause anticholinergic effects is
small and, more recently, there have been suggestions that sertindole may
have beneficial effects on cognition.
Activity Goal: To provide evidence-based educational information regarding the global prevalence, recognition, and management of depression
with co-morbid anxiety.
Target Audience: This global initiative will target physicians worldwide
through affiliations with associations and other medical centers of excellence.
Determination of Need: Need for this activity was determined by survey of the target audience, review of the literature and current trends and
suggestions from past program participants.
supported by an unrestricted educational grant from H. Lundbeck

A/S
SA-06-01
Pedro Delgado
University of Texas, Dept. of Psychiatry, San Antonio, TX, USA
SA-06
Closing the Global Performance Gap in
Managing Major Depressive Disorder
and Co-morbid Anxiety
Overall Statement of Need
Major depressive disorder (MDD) is now the fourth-leading cause of the
global disease burden and the leading cause of disability worldwide;
WHO expects that depression will be the second leading cause of disability after heart disease by 2020.1,2 Cost-effective interventions are available, but do not often reach those who need them because of a number
of overwhelming challenges in low-resource settings--including lack of
facilities and trained mental health personnel, questions about effective
population-based screening, and the general stigma surrounding mental
disorders. Generalized anxiety disorder (GAD) is a chronic, disabling disorder associated with substantial personal, societal, and economic costs.
3 Co-existing GAD in depressed patients may worsen the outcome by
increasing the rates of suicide, worsening overall symptoms, conferring a
poorer response to treatment, increasing the number of medically unexplained symptoms, and increasing functional disability. The comorbidity of
GAD with MDE has been of special interest because of the high level of
comorbidity and the status of MDE as one of the most burdensome disorders worldwide.4 In this live activity, the faculty experts will review the
importance of early recognition of MDD and comorbid anxiety and focus
on innovative strategies to manage these challenging comorbidities in
patients from both developed and developing countries.
1. Hyman S, et al. Mental Disorders. In: Disease Control Priorities in
Developing Countries, 2d ed., ed. Dean T. Jamison et al. New York:
Oxford University Press, 2006. 2. The WHO World Mental Health Survey
Consortium. Prevalence, severity, and unmet need for treatment of mental disorders in the World Health Organization world mental health surveys. JAMA 2004;291:2581-2590 3. Kessler RC, Chiu WT, Demler O,
Walters EE. Prevalence, severity, and comorbidity of 12-month DSM-IV
disorders in the National Comorbidity Survey Replication. Arch Gen
Psychiatry 2005;62:616-627. 4. World Health Organization (WHO),
Gender and Women's Mental Health (1997), accessed online at
www.who.int. Accessed 10/23/2006
Learning Objectives
SA-06-02
Julio Licinio
University of Miami, Dept. of Psychiatry, Miami, FL, USA
supported by an unrestricted educational grant from Wyeth

Pharmaceuticals
SA-08
Bipolar Illness: Beyond major depression and
euphoric mania
The diagnosis and treatment of bipolar disorder (BD) has been inconsistent and frequently misunderstood in recent years. Both the underdiagnosis of BD and its frequent misdiagnosis as unipolar major depressive disorder (MDD) appear to be problems in patients with BD. Underdiagnosis
results from clinicians' inadequate understanding of manic symptoms,
from patients' impaired insight into mania, and especially from failure to
involve family members or third parties in the diagnostic process. Some of
the underdiagnosis problem may also result from lack of agreement
about the breadth of the bipolar spectrum, beyond classic type I manicdepressive illness. The diagnosis would give greater weight to family history and antidepressant-induced manic symptoms and would apply to
non-type I or II bipolar illness, in which depressive symptom, course, and
treatment response characteristics are more typical of bipolar than unipolar illness. Furthermore, some specials forms of bipolar disorder - mixed
states, rapid-cycling and atypical bipolar disorder- are of major clinical and
research relevance.
SA-08-01
Frederick Goodwin
George Washington Univ. Medical Center, Bethesda, MD, USA
At the end of this CE activity, participants should be able to:
Identify three patient barriers that contribute to the performance

gap noted by the World Health Organization
Provide clinicians with tools and strategies to improve the delivery

of costeffective interventions for patients with co-morbid anxiety
and depression
Implement innovative and novel teaching approaches to improve the

global performance gap in the diagnosis and management of
depression
and co-morbid anxiety
supported by an unrestricted
GlaxoSmithKline Chile
educational
grant
from
223
AUTHOR INDEX
A
Abdeldayem, H. ..................................................69
Abdollahian, E. ..................................................144
Abdul Rahman, A. H. ..............71, 88, 92, 121, 169
Abreu, P. ............................................................146
Abushayeva, M. ..................................................94
Acea, R. ..........................................................213
Acua, A. ..........................................................105
Adamcova, K. ....................................................161
Adelson, M. ........................................................96
Ader, M. ..............................................................47
Adewuya, A. ........................................................76
Agius, M. ..........................................................138
Agote, D. ..........................................................173
Agranat-Meged, A. ............................................123
Ahmed, S. ..........................................................189
Ahrendts, J. ........................................................179
Aigner, M. ............................................................45
Ais, E. ........................................................101, 102
Akahane, A. ......................................................151
Alajbegovic, A. ..........................................109, 214
Alajbegovic, S. ..........................................109, 214
Alda, M. ..................................................37, 38, 39
Alderete, M. ......................................................188
Alderman, J. ......................................................188
Alegria, P. ..................................................176, 208
Alex, J. ................................................................58
Alexander, H. ......................................................82
Alfonso, Y. ........................................................122
Allen, C. ............................................................205
Allen, P. ..............................................................210
Allgulander, C. ..................................................113
Almeida, J. ........................................................178
Almeida Silva, V. de ............................123, 213, 224
Almonte, J. C. ....................................................103
Alphs, L. ............................................135, 144, 159
Altamura, C. ..........................................27, 52, 181
Alvarado, M. T. ..................................................140
Alvarez, A.R. ......................................................172
Alvarez, C. ........................................................195
Alvarez, E. ..................................................167, 199
Alves-Neto, W. ..................................................176
Alzate, M. ..........................................................217
Amaro Jr., E. ................................................42, 178
Amaro, E. ..........................................................178
Aminzadeh, F. ....................................................126
Amminger, G. P. ................................................135
Amminger, P. ......................................................138
Amthauer, H. ....................................................175
Anderer, P. ....................................................45, 174
Androsiuk, W. ....................................................132
Andruskevicius, S. ..............................................104
Anghelescu, I.-G. ................................................110
Anilkumar, A. ....................................................139
Anker, J. ..............................................................97
Araujo, D. ..................................................143, 176
Araya, R. ............................................................192
Araya, S. ............................................................188
Araya, V. ............................................................182
Arizaga, R. ..........................................................20
Armijo, A. ..................................................188, 204
Armony, J. ............................................................35
Arosio, B. ............................................................27
Arques Egea, S. ..................................................203
Arzt, E. ................................................................18
Aschauer, H. ..............................................135, 166
Asenbaum, S. ......................................................42
Assimov, M. ......................................156, 208, 215
Assion, H.-J. ......................................................147
Atmaca, M. ........................................................185
Attarbaschi, T. ......................................................42
Aukes, M. ............................................................76
Avgustin, B. ......................................138, 140, 196
Ayuso Gutierrez, J.-L. ..........................................17
Aziz Jemain, A. ........................71, 88, 92, 121, 169
B
Babakhanyan, A. ..........................................92, 106
Babic, D. ......................................................67, 116
Babinkostova, Z. ................................................128
Bachmann, S. ....................................................156
224
Bader, M. ..........................................................117
Baeken, C. ..........................................................79
Baewert, A. ..........................................................60
Bagby, R.M. ........................................................111
Baghai, T. C. ......................................................104
Bahk, W.-M. ......................................................169
Bai, P. ................................................................145
Bai, Y. M. ..........................................................187
Bai, Y.-M. ..........................................................158
Baiget, M. ..........................................................167
Baji, I. ..................................................................65
Baker, G. ............................................................210
Bakker, A. ..........................................................207
Balazic, J. ..........................................................167
Ball, S. ................................................................113
Ballesteros, S. ....................................108, 119, 120
Balslev Jorgensen, M. ........................................165
Bang, S.-K. ........................................169, 177, 201
Baptista, T. ..........................................................76
Barbosa, C. ........................................................138
Barboza, A. ........................................................219
Barcikowska, M. ................................................132
Barczak, A. ........................................................132
Bares, M. ..................................................161, 172
Baroni, S. ..........................................................214
Barr, C. ....................................................12, 65, 70
Barra, F. de la ................................................53,121
Barrachina, J. ......................................................199
Barrantes, C. ......................................................216
Barros, I. ............................................................207
Bartenstein, P. ......................................................83
Bartholomew, J. ................................................122
Batra, N. ............................................................210
Battaglia, S. ........................................................202
Bayerl, M. ..........................................................177
Bayle, F. ................................................................33
Becker, A. ............................................................45
Becker, J. ............................................................138
Bedarida, G. ......................................................104
Bellina, V. ............................................................52
Bellodi, L. ............................................................12
Belohlavek, O. ......................................................78
Bender, M. ........................................................118
Benegal, V. ..........................................................58
Benguettat, D. ....................................................206
Benites, F. ..................................................132, 138
Benitez-Estevez, A. ............................................146
Benito, A. ............................................................86
Benito, N. ..........................................................188
Beretta, M. ........................................................161
Bergemann, N. ....................................................75
Berger, G. ..........................................................125
Berger, M. ......................................................11, 12
Bernik, M. ..........................113, 117, 197, 198, 222
Bernstein, H.-G. ................................................150
Bert, B. ..............................................................133
Besche-Richard, C. ............................................136
Bienna, A. ..........................................................204
Binneman, B. ......................................................144
Bins, H. ..............................................................215
Bio, D. ................................................................100
Bishnoi, M. ........................................113, 201, 203
Bjerkenstedt, L. ............................................25, 151
Blanco, C. ..........................................................114
Blazevic-Zelic, S. ................................................218
Blednov, Y. ..........................................................94
Blier, P. ................................................................84
Blinc, M. ............................................................138
Blom, H. ..............................................................76
Bobek - Billewicz, B. ..........................................154
Bobes, J. ..............................................................10
Bodnar, B. ............................................................93
Boer, J. A. den ......................................................13
Bogerts, B. ..................................................78, 150
Bogovi, A. ..........................................................204
Bogush, Y. ..........................................................166
Bokhan, N. ............................................92, 94, 211
Bonati, M. T. ........................................................ 80
Bonci, A. ..............................................................98
Bondy, B. ............................................................104
Bonelli, R. M. ....101, 128, 129, 133, 164, 173, 174
..................................................................183, 199
Borduqui, T. ........................................................143
Borges-Gargano, C. ............................................146
Borja, H. ............................................................212
Borkowska, A. ..............................................38, 130
Born, C. ............................................................104
Bosi, M. F. E. ................................................52, 181
Bourdieu, M. ......................................................150
Bourhis, E. ..........................................................142
Bourin, M. ............................................................85
Boyajyan, A.S. ....................................................148
Bozina, N. ..........................................................141
Bozkurt, A. ..........................................................65
Brand, S. ........................................................18, 45
Brathwaite, J. ........................................................9
Braus, D.F. ..........................................................175
Bravo, A. ............................................................109
Bravo, E. ............................................................176
Bravo-Mehmedbasic, A. ....................117, 184, 214
Brecht, S. ..........................................................190
Bressan, R. A. ....................................................138
Breznoscakova, D. ................................................93
Briley, M. ............................................................221
Brunovsky, M. ....................................149, 162, 172
Bubenikova-Valesova, V. ............................186, 202
Bubl, E. ..............................................................179
Buble, T. ............................................................195
Bchel, C. ..........................................................175
Buchholz, H.-G. ....................................................83
Buddensiek, N. ..................................................196
Buechert, M. ......................................................179
Bukowska, A. ....................................................150
Bulbena, A. ........................................................213
Bulut, M. ............................................................215
Bunevicius, R. ......................................................34
Buoli, M. ......................................................52, 181
Burns, J. .............................................................. 77
Busatto, G. ..........................................42, 176, 178
Bustamante, F. ......................................................95
Bustamante, I. ....................................................217
Bustamante, M. L. ..............................................166
Busto, U. ............................................................7, 8
Butman, J. ..........................................................179
Byszewski, A. ....................................................126
C
Cabanes, L. ..........................................................86
Cabezaz, F. ........................................................173
Cabrera, J. ..........................................................155
Caffo, E. ..............................................................80
Cahn, W. ..............................................................29
Calderon, A. ......................................104, 119, 120
Caldirola, D. ........................................................12
Callicott, J. ..........................................................83
Calovska Samardziska, V. ....................................191
Calvo Prandi, M. S. ............................................100
Calv, M. ..................................................102, 150
Calvo-Malvar, M.M. ............................................146
Calzada Reyes, A. A. ..........................................115
Camacho Lopez, P. A. ................................122, 124
Camacho, A. ......................................................100
Camponovo, D. ..................................................167
Campos, M. ......................................................212
Canisius, S. ..........................................................73
Canitano, R. ........................................................69
Cannon, D. M. ....................................................11
Cano, J. F. 136, ..................................................217
Carey, P. ............................................................118
Carlini, M. ..........................................................214
Carr, V. ..............................................................157
Carrasco, J. ..........................................................15
Carrizo, E. ............................................................76
Carroll, M.E. ........................................................97
Cassel, W. ............................................................45
Cassin, B. ............................................................60
Castelli, P. ..........................................................158
Castello Gasco, J. ..............................................203
Castiglioni, M. ....................................................202
Castilla-Puentes, R. .......................... 62, 64, 70, 140
Castilla-Puentes, S. ............................................140
Castilla-Puentes, W. ............................................140
Castillo, C. ........................................................135
Castro, J. ..............................................................62
AUTHOR INDEX
Catena, M. ........................................110, 119, 214

Cattaneo, E. ........................................................27
Cavalleri, F. ..........................................................80
Cazorla, P. ..........................................................135
Cazzullo, C. L. ......................................................27
Cebasek Travnik, Z. ............................................196
Celis, A. ............................................................105
Cendales, R. ..............................................136, 217
Centanni, L. ......................................................185
Cerqueira, C. ......................................................178
Ceskova, E. ..........................................................30
Cetkovich-Bakmas, M. ..........................................34
Chae, J.-H. ........................................................169
Chainho, J. ................................................105, 216
Chaki, S. ..............................................................51
Chang, H.-A. ......................................................149
Chang, I.-S. ........................................................200
Chang, W.-H. ....................................................187
Change, C.-C. ....................................................149
Chatton, A. ................................................102, 193
Chaudhry, H. R. ............................................75, 159
Chazeron, I. de ..................................................126
Chee, I.-S. ..................................................137, 139
Chee, K. Y. ..........................................................75
Chei Tung, T. ......................................................103
Chele, G. ................................................96, 97, 99
Chen, C.-C. ........................................................143
Chen, C.-L. ........................................................149
Chen, E..Y.H. ......................................................171
Chen, J.-Y. ........................................................187
Chen, T. T. ..........................................................187
Cheng, S.-T. ......................................................111
Chereau-Boudet, I. ............................................126
Cheung, B. K. L. ................................................206
Cheung, C. ........................................................171
Chieri, P. ..............................................................40
Chinea, E. ..................................................102, 207
Chirinos, A. ........................................................172
Chirita, R. ................................................96, 97, 99
Chirita, V. ................................................96, 97, 99
Chittiprol, S. ..............................................109, 146
Chiu, F.-Y. ..........................................................158
Chivite, S...............................................................22
Chodakowska-Zebrowska, M. ............................132
Choi, M.-J. ........................................110, 166, 189
Choi, S. ................................................................93
Choi, Y. ..............................................................131
Chopra, K. ................................................201, 203
Chou, K.-H. ........................................................158
Chou, Y.-H. ..................................................86, 158
Chour, W.-Y. ......................................................143
Christodoulou, C. ..............................................145
Chu, E. ..............................................................192
Chua, S. ............................................................171
Chung, J. H. ........................................................23
Ciampa, G. ................................................119, 214
Cid, C. ..............................................................188
Ciobanu, A. M. ..................................................100
Cizmovic, B. ......................................................160
Clavero, R. ........................................................212
Clavijo, N. ..........................................................188
Clays, F. ..............................................................206
Clerici, M. ............................................................27
Clivio, A. ..............................................................27
Cogliati, F. ............................................................80
Cohen, H. ..........................................................182
Cohen, M. ..........................................................157
Cohen, S. ............................................................ 65
Conesa, H.A. ......................................................150
Consoli, G. ................................................110, 119
Corchs, F. ..........................................................117
Crcoles, D. ......................................................213
Cordeiro, Q. ..............................................103, 176
Cordes, J. ..........................................................145
Cordoba, R. N. ..................................................136
Crdoba, R. N. ..................................................217
Cornish, K. ................................................168, 169
Cornutiu, G. ......................................................147
Cornutiu, O. ......................................................147
Corrales, A. ..........................................................40
Correa, E. ..............................................10, 17, 112
Corregiari, F. ..............................113, 117, 197, 198
Cortes, A. ..........................................................167
Cosacow, D. ......................................................173
Costa Leite, C. ....................................................42
Costa, P.T. ..........................................................111
Cosyns, P. ............................................................53
Courtecuisse, C. ................................................190
Covarrubias, M. I. ..............................................188
Craddock, N. ........................................................65
Craig, I. ................................................................65
Crawford, T. ......................................................139
Crayton, J.W. ......................................................67
Crippa, J. A. ................................................42, 143
Croenlein, J. ......................................................190
Cuervo, C.-V. ......................................................136
Cuesta, M. J. ........................................................22
Cumming, P. ........................................................83
Cunha, M. G. ............................................109, 208
Curran, H. V. ............................................94, 95, 96
Czekalla, J. ........................................134, 146, 198
D
D'haenen, H. ........................................................79
Dachesky, D. ......................................................128
Damjanovic, A. ..................................................152
Darczy, G. ..........................................................65
Dashniani, M. ....................................................162
Dasi, C. ..............................................................148
Davidson, J. ........................................................114
Debieuvre, C. ....................................................190
Deitcher, C. ........................................................123
Del Debbio, A. ..................................................110
Del-Ben, C. ................................................176, 199
Delgado, P. ........................................................223
DeLisi, L. ..............................................................28
Dell'Osso, B. ................................................52, 181
Dell'Osso, L. ..............................................110, 214
Deluca, V. ............................................................12
Demetrio, F. N. ..................................................103
Dempster, E. ........................................................70
Demyttenaere, K. ..............................................190
Deng, Y. ............................................................171
DeRaedt, R. ..........................................................79
Derost, P. ............................................................126
Desai, N. G. ........................................................200
Desaiah, D. ................................................190, 191
Detke, M. ..........................................................113
Dezeljin, M. ..................................................67, 116
Dhoine, K. ..........................................................218
Di Nicola, M. ........................................................93
Diamond, I. ..........................................................98
Diaz Martinez, C. ................................................93
Diaz Martinez, L. A. ............................................124
Daz, D. ..............................................................207
Diaz, E. ..............................................................137
Diaz-Mesa, E. ....................................................146
Diehl-Schmid, J. ....................................................72
Dielentheis, T. F. ................................................177
Diemer, N. ..........................................................165
Diez, J. ..............................................................174
Dillingh, G. ........................................................207
Dimellis, D. ........................................................195
Dinan, T. G. ................................................208, 209
Diniz, B. O. ........................................................103
Diniz, J. ..............................................................215
Divos, H. ..............................................................45
Divosevic, S. ......................................................151
Djazayeri, S. ......................................................205
Djedovic, J. ........................................................160
Dmitrzak-Weglarz, M. ..........................................38
Dobrowolny, H. ..................................................150
Dodd, P. ................................................................8
Dodel, R. ..............................................................73
Doknic, M. ........................................................152
Dolnicar, R. ..................................................72, 167
Dominguez, J.I. ..................................................172
Donoso, E. ..........................................................95
Dordevic, V. ........................................................195
Dossenbach, M. ................................................202
Douzenis, A. ......................................................145
Dragasek, J........................................................... 93
Dremencov, E. ......................................................84
Dremov, G. ........................................................211
Dresel, S. ............................................................178
Drimalova, M. ......................................................93
Dro, W. ..............................................................130
Drzezga, A. ..........................................................72
Dudczak, R. ..........................................................42
Duenas, H. ........................................................105
Duffy, A. ........................................................37, 38
Duletic, N. ..........................................................160
Dumitrescu, M. R. ..............................................203
Dunlop, B. ..........................................................189
Dunner, D. ................................................189, 190
Duran, F. ............................................................176
Durif, F. ..............................................................126
DUrso, N. ..........................................................181
Dwivedi, Y. ........................................................161
Dyachenko, L. ......................................................98
Dyck, R. van ........................................................80
Dzubur Kulenovic, A. ........................................117
E
Eap, C. ..............................................................194
Ebeling, H. ..........................................................75
Eberhard, J. ..................................96, 149, 153, 186
Ebert, D. ............................................................179
Ebner, N. ..............................................................60
Ebner, S. ..............................................................88
Eckert, A. ............................................................18
Edman, G. ............................................................25
Eguiluz, I. ..........................................................135
Ekici, G. ..............................................................215
El Mansari, M. ......................................................84
El Masri, D. ........................................................177
El-Khatib, M. ......................................................219
ElFakih, Y. ............................................................76
Elliott, M. ............................................................28
Ellis, J. ..................................................................37
ElNahas, G. M. 161
Emrich, H.M. ......................................................196
Emsley, R. ............................................................29
Encina, C. ..........................................................155
Eng, S. ..............................................................141
Enterman, J. ......................................................137
Entsuah, R. ........................................................114
Epelbaum, A. ....................................................194
Erausquin, G.A. de ............................................150
Escobar Sanchez, M. ..................................122, 124
Escobar, J.I. ........................................................150
Eser, D. ..............................................................104
Espinosa, C. ......................................................155
Essig, M. ............................................127, 156, 174
Ethesdam, S. .......................................................... 9
Ettinger, U. ........................................................139
Eyck, D. van ........................................................47
F
Faich, G. ............................................................141
Fallon, J. ..............................................................83
Faradoni, F. ........................................................136
Faravelli, C. ........................................................119
Faravelli, L. ........................................................ 119
Farmer, A. ............................................................65
Faunes, M. ........................................................188
Fedorenko, O. ..............................................92, 150
Feige, B. ................................................11, 12, 179
Feldon, J. ....................................................24, 153
Fellmann, H. ........................................................78
Feng, Y. ................................................................65
Ferdousi, T. ........................................................189
Ferguson, J. ................................................189, 190
Fernandes, S. ............................................105, 216
Fernandez Huerta, J. M. ....................................211
Fernandez Sola, J. ..............................................211
Fernndez, I. ......................................................207
Fernandez, L. ....................................................137
Fernandez, V. ......................................................76
Ferrao, Y. ..........................................................215
Ferrari, G. C. de ................................................168
Ferreira, C. ........................................................176
Ferreira, J. ............................................................95
Ferris, C. ..............................................................19
Fian, R. ..............................................................101
Fiedler, J. ....................................................106, 182
225
AUTHOR INDEX
Fierro, M. ..........................................................136
Fiestas, F. ............................................................217
Figueiredo, L. A. P. de ........................................208
Figueroa, E. ..........................................................59
Fink, H. ..............................................117, 133, 171
Fink-Jensen, A. ....................................................97
Fischer, G. ............................................................60
Fitzgerald, P. ..............................................208, 209
Fleming, K. ........................................................144
Florenzano, N. ....................................................150
Florenzano, R. ............................104, 108, 119, 120
Flores, C. ............................................................171
Flores, D. ............................................................185
Flyckt, L. ..............................................................25
Folnegovi Grosi, P. ..............................................204
Folnegovic-Smalc, V. ..................................127, 201
Folnegovsmalc, V. ..............................................204
Ford, J. ................................................................44
Forlenza, O. ........................................................126
Fortes, S. ............................................................ 212
Fossati, P. ............................................................35
Franciskovic, T. ..................................................147
Franco Lopez, J. A. ....................................122, 124
Franke, L. ..........................................................175
Freedman, R. ........................................................37
Freitas, C. ..........................................................132
Fresard, E. ..................................................193, 206
Friedman, E. ..............................................189, 190
Friedreich, S. ................................................84, 177
Fritsch, R. ..........................................106, 182, 192
Fritz, R. ..............................................................106
Fuchs, K. ............................................................166
Fuentes, M. ........................................................192
Fuentes, P. ..........................................................208
Fullerton, C. ......................................................103
Furey, M. ..............................................................11
G
Gaag, van der ....................................................137
Gabilondo, A. ....................................................213
Gabryelewicz, T. ................................................132
Gado, M. ..........................................................141
Gadoros, J. ....................................................65, 70
Gaebel, W. ....................................................26, 28
Galeano, E. ..........................................................36
Galeazzi, T. ..........................................................76
Galeno, R. B. ..................................................29, 54
Galili-Wiesstub, E. ..............................................123
Gallardo, R. ........................................................188
Galleguillos, F. ....................................................166
Galli, E. ................................................................64
Gallo, C. ............................................................217
Galvan, J. ..........................................................173
Galvez, P. ..........................................................188
Gangadhar, B. N. ........................86, 109, 146, 163
Garcia, R. ..........................................................155
Garcia-Amador, M. .............................................. 62
Garcia-Aquirre, J. L. ..............................................49
Garca-Barriga, C. ................................................49
Garcia-Campayo, J. ............................................ 212
Garcia-Hernandez, A. ........................................137
Garca-Ribera, C. ................................................213
Gardner, M. ........................................................158
Garver, K. ............................................................82
Gattaz, W. ............................................24, 57, 197
Gau, S.-F. ............................................................50
Gaviria, S. ............................................................10
Gaysina, D. ..........................................................65
Geier, C. ..............................................................82
Geisler, P. ............................................................210
Gelazonia, L. ......................................................162
Gelenberg, A. ............................................189, 190
Gentil Filho, V. ....................................................178
Gentil Savoia, M. ................................................113
Gentil, V. ............................................................178
Gentile, S. ..........................................................193
George, M. ..........................................................36
Gergerlioglu, H. S. ..............................................215
Geri, S. ................................................................93
Gerstl, F. ..............................................................84
Gerwe, M. ................................131, 134, 146, 198
Gesierich, T. ........................................................177
226
Gheorghe, M.-D. ..................................................76

Giannaccini, G. ..................................................214
Gierski, F. ..........................................................136
Giesel, F. ....................................................127, 156
Giesler, M. ............................................45, 73, 118
Gil-Ad, I. ............................................................182
Gins, J. M. ........................................................213
Glaescher, J. ......................................................175
Glasinovic, A. ......................................................95
Gliddon, L.A. ........................................................97
Godas Sieso, T. ..................................................211
Goddard, A. ......................................................197
Gold, L. H. ........................................................ 101
Goldzweig, G. ....................................................123
Golia, A. ............................................................110
Goma, M. ..........................................................167
Gomez Gil, E. ....................................................211
Gomez-Restrepo, C. ..........................................100
Gonzales, C. ......................................................212
Gonzalez Alemn, G. ........................................150
Gonzalez, L. ......................................................217
Goodwin, F. ..................................................5, 223
Gordon, H. ..........................................................53
Gorelick, D. A. ..................................................5, 8
Gorenstein, C. ....................................................178
Gorini Amedei, S. ..............................................119
Gorshkova, L. ....................................................190
Goudochnikov, V. ..............................................200
Gournellis, R. ....................................................145
Graa, J. ....................................................105, 216
Gracia, R. ..........................................102, 137, 207
Graeff, F. ....................................................176, 199
Graovac, M. ......................................................147
Grassi, M. ............................................................12
Graulich, A. ........................................................158
Green, M. ............................................................62
Grkovic, J. ..........................................................218
Grof, P. ................................................................37
Groleger, U. ........................................................106
Grosic, V. ............................................................204
Grosjean, B. ........................................................59
Gruber, G. ............................................................45
Grunbaum-Novak, N. ........................................182
Grnder, G. ....................................................41, 83
Grzyzwa, A. ..............................................154, 159
Gschaider, S. ................................................75, 159
Guapo, V. ..........................................................176
Gubka, U. ............................................................ 78
Guduri, S. ............................................................59
Guerra, M. ..........................................................19
Guerreiro Anastacio, M. ............................107, 152
Guerrero, G. ......................................................150
Guffanti, G. ..........................................................80
Guillermo, L. ........................................................86
Guirao, M. ........................................................179
Gur, C. ............................................................5, 28
Gur, R. ............................................................5, 28
Gustov, A. ..........................................................214
Guterres, L. ........................................................215
Gutierrez Ponce De Leon, F. ................................211
Gutierrez, M. ......................................................135
Gutierrez, R. S. ..................................................135
Gutt, E. ..............................................................100
H
Haag, A. ........................................................45, 73
Haberkorn, U. ....................................................127
Haefner, S. ........................................................104
Hageman, I. ......................................................165
Hahn, S.-W. ........................................................189
Hahshemizadeh, H. ..............................................88
Hajek, T. ........................................................ 37, 38
Hallak, J. ............................................................143
Hamann, M. ......................................................171
Han, B. ..............................................................145
Han, D. H. ............................................................93
Han, J.-H. ..........................................................210
Han, S. I. ............................................................106
Han, S. W. ....................................................46, 190
Hanlon, M.-C. ....................................................123
Hanssens, L. ........................................................47
Hanstock, C. ......................................................210
Hardy, J. ............................................................168
Hargarter, L. ..............................................146, 198
Harris, A. ..............................................................94
Hartford, J. ........................................................113
Hartman, C. ........................................................13
Hascot, M. ..........................................................85
Hashempour, Z. ..................................................217
Hashimoto, R. ......................................................21
Hasna, A. ............................................................90
Hata, T. ..............................................................151
Hatzinger, M. ................................................18, 45
Haupt, D. ............................................................48
Hauser, J. ............................................................38
Havle, N. ............................................................212
Hay, E. ................................................................197
Heffernan, T. ................................................60, 122
Heijden, F. van der ..............................................207
Heijer, M. den ......................................................76
Heinimaa, M. ......................................................75
Heiskala, J. ........................................................164
Hemmeter, U. ..................................18, 45, 73, 118
Henning, J. ........................................................179
Henriquez, H. ....................................................167
Henry, B. ............................................................143
Henry, J. ..............................................................96
Henry, M. ..................................102, 137, 146, 207
Henze, M. ..........................................................127
Hernandez- Garcia, D. ........................................146
Herold, N. ..........................................................175
Herpertz, S. ..........................................................15
Herpertz-Dahlmann, B. ........................................ 55
Herranhof, B. ....................................128, 129, 133
Herrera, F. ............................................................10
Herrera, L. ..................................................106, 182
Hess, L. ..............................................................199
Hesslinger, B. ......................................................179
Hettema, J. M. ....................................................14
Hert, M. de ....................................................33, 47
Hietala, J. ............................................................41
Higuchi, Y. ..........................................................31
Hill, C. D. ..........................................................135
Hirschfeld, R. ..............................................189, 190
Ho, A. M. C. ......................................................206
Hoda, F. ................................................................65
Hodjat, S. K. ......................................................144
Hdl, A. ............101, 128, 129, 133, 164, 173, 174
..................................................................183, 199
Hodler, C. ..........................................................142
Hoencamp, E. ....................................................137
Hoffman, K. ......................................................216
Hofmann, P. ......................................................101
Hohagen, F. ..........................................................85
Hojaij, C. ..............................................................29
Holik, A. ................................42, 84, 117, 176, 177
Holl, E. ..............................................................164
Hollis, J. ................................................................37
Holsboer-Trachsler, E. ....................................18, 45
Holston, E. ..........................................................72
Holzer, M. M. ......................................................87
Hong, K. S. ................................................140, 141
Hong, S.-C. ........................................................210
Hoof, J. van ..........................................................89
Hoogendijk, W. ....................................................80
Hoogendoorn, M. ................................................76
Hopf, W. F. ..........................................................98
Hora, J. ..............................................................205
Horacek, J. ............................ 78, 88, 149, 161, 202
Hosak, L. ............................................................204
Hschl, C. ....................................................78, 149
Hossain, I. ............................................................90
Hotsenpiller, G. ....................................................67
Hotujac, L. ............................................................63
Hsiao, C.-C. ........................................................107
Hsiao, M.-C. ......................................................209
Huang, S.-Y. ......................................................149
Humberto, J. ......................................................152
Hungria, J. O. Soares ..........................................132
Hunt, A. ......................................................72, 127
Hunter, M. ........................................................157
I
Ibach, B. ............................................131, 134, 146
AUTHOR INDEX
Idemudia, E. E. ..................................................159
Idris, N. F. ..........................................................143
Igimi, H. ............................................................157
Igoa, A. ......................................................101, 102
Ikeda, M. ..............................................................21
Ilinca, M. ..................................................96, 97, 99
Ille, R. ................................................................128
In-Ho, P. ....................................................177, 201
Indran, T. ..................................71, 88, 92, 121, 169
Inoue, M. ....................................................98, 157
Inoue, S. ..............................................................98
Inoue, Y. ..............................................................98
Intzausti, A. ........................................................146
Iserhard, R. F. ......................................................180
Ising, M. ..............................................................18
Islam, N. ..............................................................90
Iturra, P. ....................................................166, 197
Iturria, I. ....................................................119, 120
Ivanova, S. ....................................92, 94, 150, 183
Ivanovic-Zuvic, F. ..........................................10, 112
Ivanovic-Zuvic, N. ..............................................112
Iwata, N. ..............................................................21
J
Jabbi, M. ..............................................................13
Jabs, B. ................................................................23
Jagsch, R. ..............................................................60
Jain, S. ..............................................................141
Jakovljevic, M. ..................63, 67, 89, 91, 116, 132
Janas-Kozik, M. ....................................................87
Jandl, M. ..............................................................64
Janelle, E. ..........................................................113
Jang, H.-J. ..........................................................191
Janiri, L. ........................................................56, 93
Jankovic, P. ..........................................................93
Japaridze, N. ......................................................162
Jara Opazo, C. ..................................................210
Jara, C. ..............................................................188
Jrvelin, M.-R. ......................................................75
Jasovic Gasic, M. ................................................152
Jeon Lan, K. ......................................................139
Jeon, Y. W. ........................................................106
Jeong, J.-H. ........................................................210
Jeong, Y.-J. ........................................................166
Jerez, S. ....................................................166, 197
Ji, M.-Y. ..............................................................189
Jiang, Q. ............................................................114
Jimenez, M. ........................................................166
Jina, A. ......................................................187, 188
John, J. P. ..........................................................141
Johnson, L. L. ...................................................... 37
Johnston, P. ........................................................157
Jones, P. B. ..........................................................75
Jong, S. de ..........................................................80
Jonovska, S. ......................................................184
Jonovski, N. ........................................................184
Jordaan, I. ..........................................................118
Joukamaa, M. ......................................................75
Jovanovic, N. ..............................................141, 151
Juchnowics, D. ..........................................111, 207
Jun, T.-Y. ..............................................22, 152, 169
Jung, H. ....................................................170, 196
Jung, H.-Y. ........................................................191
Jung, Y.-E. ..........................................................169
K
Kader, L. ............................................................148
Khknen, S. ......................................................164
Kahn, R. ..............................................................76
Kaibuchi, K. ..........................................................21
Kaiser, E. ......................................................72, 127
Kalische, R. ........................................................175
Kane, J. ..............................................................141
Kang, R.-H. ..........................................46, 166, 190
Kaparnai, K. ........................................................70
Kapfhammer, H. P. ............101, 129, 173, 174, 199
Kapornay, K. ........................................................65
Karakula, H. ..............................................154, 159
Karlidere, T. .......................................................... 65
Karwautz, A. ......................................................125
Kaschka, W. ........................................................64
Kasparek, T. ..........................................................30
Kasper, S. ........6, 42, 52, 57, 82, 84, 117, 166, 176
.................................................................. 177, 222
Kaufmann, J. ........................................................78
Kaufmann, R. ....................................................135
Kawas, O. ..........................................................105
Kawasaki, Y. ........................................................ 31
Ke, C.-L. ............................................111, 114, 143
Kean, M. ............................................................139
Keller, D. ............................................................144
Keller, M. ..................................................189, 190
Kema, I. ..............................................................13
Kennedy, A. ........................................................97
Kennedy, J. ..........................................7, 12, 65, 70
Kennedy, J. L. ....................................................7, 9
Kennedy, S.H. ....................................................111
Kesebir, S. ..........................................................108
Keshavan, M. ......................................................31
Khalaf, M. ............................................................70
Khan, R. ............................................................206
Khazaal, Y. ................................102, 193, 194, 206
Khoyetsyan, A. ..................................................148
Khudabux, J. ......................................................210
Kienbacher, C. ....................................................125
Kim, H. ..............................................................170
Kim, J. J. ............................................................152
Kim, S. H. ..........................................................170
Kim, S.-Y. ..........................................................191
Kim, Y.-K. ..........................................................141
Kindler, J. ..........................................................166
King, N................................................................... 9
Kirakosyan, A. ..............................................92, 106
Kishimoto, T. ........................................................98
Kiss, E. ..........................................................65, 70
Kitamura, S. ........................................................98
Kitchener, N. ..................................................69, 70
Klasik, A. ....................................................118, 205
Klein, E. ................................................................16
Klein, F. ................................................................34
Klein, N. ..............................................................42
Kletter, K. ..................................................117, 176
Klirova, M. ........................................................164
Klitzing, K. von....................................................227
Knezevic, J. .......................................................... 67
Koch, N. ..............................................................85
Kochetkov, Y. ....................................................110
Kocmur, M. ..................................................90, 138
Kocsis, J. ....................................................189, 190
Koenig, B. ............................................................87
Kofidis, N. ..........................................................195
Kogan, C. ..........................................................168
Kohler, C. ............................................................28
Koic, E. ..............................................................186
Koldolbsky, N. ......................................................59
Kombian, S. ........................................................86
Komel, R. ..........................................................167
Komssi, S. ..........................................................164
Konrad, A. ........................................................125
Konstantinidis, A. ................................................52
Konupcikova, K. ................................................204
Kopecek, M. ........................78, 149, 161, 164, 172
Kopishinskaya, S. ................................................214
Koponen, H. ........................................................77
Koppitz, M. ................................................101, 129
Kordon, A. ..........................................................85
Koren, D. ............................................................16
Koren, E. ............................................................ 194
Kornetova, E. ....................................................150
Kornstein, S. ..............................................189, 190
Korszun, A. ..........................................................65
Kovacs, M. .................................................... 65, 70
Kozaric-Kovacic, D. ......................................67, 116
Kozumplik, O. ....................................................201
Krajca, V. ............................................................172
Krause, J. ..................................................169, 178
Krause, K.-H. ......................................................178
Krelling, R. ........................................................100
Kremlacek, J. ..............................................156, 174
Krenz, S. ............................................................206
Krieg, J. C. ............................................45, 73, 118
Krishnaswamy, S. ..............49, 71, 88, 92, 121, 169
Krsiak, M. ..........................................................199
Krupka-Matuszczyk, I. ..........................87, 118, 205
Kruse, A. ..............................................................73
Krysta, K. ..........................................................205
Kuba, M. ............................................................156
Kucukalic, A. ..............................109, 117, 184, 214
Khmayer, D. ...................................................... 88
Kulenovic-Dzubur, A. ..................................109, 214
Kulkarni, S. ................................................113, 201
Kulkarni, S.K. ....................................................203
Kumakura, Y. ......................................................83
Kumar, K. ..................................................109, 163
Kumari, V. ..........................................................139
Kurachi, M. ..........................................................31
Kurbanova, A. ............................................208, 215
Kurt, K. ................................................................82
Kurz, A. ................................................................72
Kushnir, V. ..............................................................8
Kweon, Y. S. ......................................................168
Kwon, O. J. ........................................................152
Kwon, Y.-J. ........................................................191
L
Ladea, M. ..........................................................203
LaFougere, C. ....................................................178
Lahera, G. ............................................................86
Laitinen, J. ............................................................77
Lamy, C. ............................................................158
Lancaster, S. ..............................................135, 159
Landers, A. M. T. ................................................209
Lanzenberger, R. ..............42, 82, 84, 117, 176, 177
Lara, M. d. Carmen ............................................105
Larach-Walters, V. ..........................................27, 54
Laranjeira, L. ......................................................107
Larizza, L. ............................................................80
Larson, E.B. ..........................................................97
Latorre Latorre, J. F. ............................................122
Lauronen, E. ........................................................75
Lavekar, G. S. ......................................................86
Lay-Son, G. ........................................................106
Layton, F............................................................. 216
Le Melledo, J.-M. ..............................................210
Lee, B.-W. ..........................................................169
Lee, C. ......................................152, 177, 201, 210
Lee, C. T. ............................................................168
Lee, C.-U. ..........................................152, 177, 201
Lee, H. K. ..........................................................168
Lee, M.-S. ..................................110, 166, 189, 190
Lee, S.-J. ............................................................140
Lee, S.-P. ............................................................210
Lee, S.-Y. ....................................................140, 141
Lee, T. ................................................................ 192
Lee, Y.-S. ..............................................93, 140, 141
LeFoll, B. ................................................................7
Leibenson, L. ......................................................123
Leisch, F. ............................................................166
Leiva, F. ..............................................................155
Lemaire, J.-J. ......................................................126
Lemanski, S. ......................................................147
Lena, F. ..............................................................151
Lendeckel, U. ....................................................150
Leonard, M. ......................................................214
Leonhard-Key, M. ................................................82
Lepage, M. ....................................................31, 35
Leri, F. ................................................................205
Levander, S. ................................96, 149, 153, 186
Levesque, D. ......................................................142
Levitt, A. ..............................................................10
Levy Neto, M. ....................................................103
Lewin, T. ............................................................157
Leyman, L. ............................................................79
Leyton, M. ..............................................................7
Li, Y. .................................................................... 72
Libiger, J. ............................................................156
Licinio, J. ............................................................223
Lieber, I. ....................................................173, 194
Liebowitz, M. ....................................................114
Liegeois, J.-F. ......................................................158
Lim, H.-K. ..........................................152, 177, 201
Lim, S.-W. ....................................................47, 113
Limosin, F. ..........................................................136
Lin, K. ................................................................200
Lin, K.-M. ............................................................50
Lin, W. ......................................................111, 114
227
AUTHOR INDEX
Lin, W.-W. ..........................................................149

Lindinger, M.A. ..................................................173
Lindstrm, E. ................................96, 149, 153, 186
Linial, M. ............................................................166
Linne, A. B. ........................................................153
Linsky, I. ..............................................................98
Lippi, J. ................................................................89
Little, K. ..............................................................60
Liu, C.-Y. ............................................................209
Liu, R. ..................................................................82
Livianos-Aldana, L. ............................................203
Ljubicic, D. ................................................154, 195
Llibre Rodriguez, J. ..............................................19
Llorca, P. M. ................................................33, 126
Lobacheva, O. ....................................................142
Lobo, D. S. S. ........................................................9
Lobo, M. ....................................................105, 216
Loginov, V. ........................................................150
Loh, E.-W. ............................................................50
Lolas Stepke, F. ......................................................5
Loncarevic, N. ....................................................109
Lopes, C. ............................................................212
Lopez de Lara, C. ................................................37
Lopez Mato, A. M. ............................................221
Lopez, S. ............................................................140
Lotto, A. ............................................................208
Loughead, J. ........................................................28
Loughland, C. ....................................................157
Louza, M. ..........................................123, 159, 213
Love, T. ................................................................59
Lowry, A. ............................................................202
Loxton, N. ..........................................................206
Lucacchini, A. .................................................... 214
Luchtman, D. ....................................................132
Luczywek, E. ......................................................132
Luna, B. ................................................................82
Lyford-Pike, A. G. ................................................36
Lykouras, L. ........................................................145
M
Macciardi, F. ..................................................80, 83
Machado Vianna, A. ..........................................113
MacQueen, G....................................................... 38
Madrigal, E. ........................................................105
Magnet, M. ........................................101, 129, 199
Magnet, M. M. ..................................................183
Magroob, . ..........................................................15
Maheux, J. ........................................................142
Maki, P. ..........................................................75, 77
Malagn, A. ......................................................213
Malhi, G............................................................... 62
Malla, A. ..............................................................30
Manasyan, N. ..............................................92, 106
Mandl, M. ............................................................45
Manes, F. ......................................................34, 35
Mangano, R. ......................................................114
Manuseva, N. ....................................................191
Marazziti, D. ..............................................110, 214
Marchi, M. ..........................................................80
Marcinko, D. ..................................................89, 91
Marcolin, M. A. ....................................................52
Mardi, A. ............................................................105
Marengo, E. ..............................................101, 102
Margaryan, S. ........................................90, 92, 106
Mari, J. ..............................................................217
Maric, N. ............................................................152
Marieiro, A. ........................................................152
Mariotti, M. ..........................................................52
Maris di Cio, S. ..................................................173
Markus, M. ..........................................................82
Maron, E. ............................................................14
Marques-Teixeira, J. ....................................152, 157
Marquez Lopez Mato, A. ....................................184
Marston, H. ................................................101, 143
Martin, F. D. C. ..................................................101
Martin, M. ..........................................................137
Martinac, M. ..........................................67, 89, 116
Martinez, J. C. ......................................................10
Martino, D. ................................................101, 102
Martinotti, G. ................................................57, 93
Martinove, M. ......................................................93
Maslov, B. ....................................................67, 116
228
Masopust, J. ..............................133, 156, 174, 204

Massimini, M. ......................................................52
Matarin, M. ........................................................168
Mathalon, D......................................................... 44
Mathis, M. A. de ................................................215
Mathis, M. E. de ................................................215
Matkovic, V. ......................................................195
Matsui, M. ..........................................................31
Matsuoka, T. ..............................................157, 172
Mattay, V. ............................................................83
Mattejat, F. ........................................................198
Matuszczyk, M. ..........................................118, 205
Matzner, H. ........................................................163
Mavinakayinahalli Neelakantach, N. ..................146
Mayilyan, K. ......................................................148
Mazanek, M. ......................................................177
Mazzotti, G. ......................................................217
McAlonan, G.M. ................................................171
McCabe, K. ........................................................157
McCarley, R. W. ....................................................43
McGuffin, P. ........................................................ 65
McGuire, P. K. ......................................................42
McKenna, P. ........................................................26
Meagher, D. ......................................................214
Medina, P. ..........................................................130
Medina, S. ..........................................................155
Medved, V. ................................................141, 151
Meehan, O........................................................... 80
Mendes, S. ................................................105, 216
Meyer, U. ..........................................................153
Meyer-Lindenberg, A. ....................................41, 83
Miceli, J. ............................................................188
Miceva Velickoska, E. ........................................191
Micheli, F. ..........................................................150
Michopoulos, I. ..................................................145
Middleton, T. ......................................................118
Mien, L. ..............................................................176
Mien, L. K. ........................................................117
Miettunen, J. ........................................................75
Miguel, E. ..........................................................215
Mihaljevic-Peles, A. ........................................63, 89
Mihanovi, M. ......................................................204
Mikova, O. .......................................................... 45
Miller-Reiter, E. ....................................................88
Mimica, N. ................................................127, 201
Minko, A. ............................................................98
Minshew, N. ........................................................82
Miranda, E. ........................................................155
Miranda-Camacho, R. ..........................................49
Mitchell, D. ........................................................221
Mittal, M. ............................................................16
Mittal, S. ..............................................................16
Mitterhauser, M. ........................................117, 176
Moeller, H. ........................................................ 134
Mohandas, E. ................................................15, 49
Mohr, P. ..............................................................164
Moilanen, I. ....................................................75, 77
Molavi, P. ..........................................................217
Molina, V. A. ........................................................55
Mller, H.J. ..........................................................84
Molnar, F. ..........................................................126
Monarde, M. ......................................................188
Monardes, J. ......................................................216
Monchablon, A. ..................................................57
Moneta, M.-E. ....................................................167
Montagrin, Y. ....................................................206
Monteiro, L. ......................................................159
Montes, C. ........................................................197
Montes, J. M. ......................................................86
Montt, E. ............................................................192
Monzon, J. ........................................................137
Morales, C. ........................................................207
Morales, M. ........................................................188
Moran-Gates, T. ................................................ 158
Morena, A. L. ....................................................137
Moreno, D. H. ....................................................103
Moreno, R. A. ....................................100, 109, 208
Morera, A. ................................................107, 146
Morgan, C. ..............................................94, 95, 96
Mori, K............................................................... 172
Morita, K. ..........................................................157
Morlock, R. ........................................................135
Morokutti, W.N. ................................................112

Morshed, N. M. ....................................................90
Moser, E. ..............................................................84
Moser, U. ..............................82, 84, 117, 176, 177
Mossaheb, N. ......................................42, 135, 138
Moya, C. ............................................................106
Mpalaskas, D. ....................................................195
Mrsic Pelcic, J. ....................................................195
Muck-Seler, D. ..........................63, 67, 89, 116, 127
Mulleners, W. ....................................................218
Mller, N. ........................................23, 32, 33, 129
Mundo, E. ....................................................27, 181
Muntjewerff, J.-W. ..............................................76
Murillo, G. ..........................................................188
Murray, G........................................................... 103
Murray, R. M. ..............................................42, 155
Murthy, K. K. ......................................................200
Musalek, M. ........................................................55
Musgnung, J. ....................................114, 189, 190
Mustapic, M. ........................................67, 116, 127
Mut, F. ..............................................................161
Myeung-Soo, K. ................................................139
N
Na, C. ..................................................................93
Nachar, R. ..........................................................188
Nachum-Biala, Y. ................................................166
Nagpal, R. ............................................................58
Nagy, N. .............................................................. 70
Nakamura, L. ......................................................109
Nakata, A. C. ....................................................215
Nambi, S. ............................................................16
Nanko, S. ..........................................................151
Nascimento, A. P. ..............................................103
Navarro Mancilla, A. A. ..............................122, 124
Naveen, M. N. ....................................................146
Neafsey, E.J. ........................................................ 67
Neill, J. C. ..........................................................143
Nekwasil, B. ......................................................118
Neovius, M. ................................................153, 186
Nibuya, M. ..........................................................16
Nielsen, M. ........................................................165
Nieto-Caraveo, A. ..............................................221
Nissen, C. ......................................................11, 12
Northoff, G. ........................................................78
Novak Sarotar, B. ..............................138, 140, 196
Novak, T. ....................78, 149, 161, 162, 164, 172
Novotni, A. ........................................................191
Nowak, G. ............................................................50
Noya-Tapia, N. ........................................................8
Nunes, P. ............................................................126
Nunez, C. ..........................................................119
O
O'Brien, S. ..................................................208, 209
O'Neill, T.S. ..................................................98, 122
Obermeyer-Pietsch, B. ........................................129
Obmann, S. ........................................................129
Oh, K.-S. ..............................................47, 113, 141
Ohlmeier, M. ......................................................196
Okribelashvili, N. ................................................159
Olarte, A. ..................................................136, 217
Olavarria, L. ........................................................208
Olave, C. ............................................................208
Olea, E. ..............................................................188
Olincy, A. ............................................................37
Olivera, S. ............................................................36
Olmos, M. ..........................................................136
Oosthuizen, P. ......................................................29
Opolska, A. ........................................................154
Ordyan, M. ........................................................106
Orellana, G. ........................................................157
Ormel, J. ..............................................................13
Oropeza Herrera, P. ............................................172
Orozco, A. ................................................137, 146
Ortega, A. ............................................................10
Ortiz, M.C. ........................................................172
Osorio, J.P. ........................................................216
Ospina-Duque, J. ..................................................39
Otti, D. V. ..........................................128, 129, 183
Owen, M. ............................................................65
Oyhamburu, P. ..................................................184
AUTHOR INDEX
Ozaki, N. ..............................................................21
Ozdemir, S. ........................................................212
Ozluk, K. ............................................................108
Ozmenler, K. N. ....................................................65
P
Pae, C. U. ..................................................152, 169
Paes de Barros Neto, T. ......................................113
Paganelli, P. ........................................................126
Paggini, R. ..........................................................119
Paik, I. H. ....................................................24, 152
Paik, J.-W. ..........................................................110
Paina, G. ............................................................147
Painold, A. ........................................................174
Paiva, A. ....................................................105, 216
Palenicek, T. ..............................................202, 205
Palla, A. ....................................................110, 119
Palova, E. ............................................................93
Panagides, J. ......................................................144
Pandey, G. ..........................................................161
Panico, R. ............................................................80
Pantel, J. ........................................................72, 73
Papageorgiou, K. ................................................138
Papp, M. ............................................................101
Paranhos Jr., A. ..................................................138
Park, C.-W. ................................................140, 141
Park, E. J. ..........................................................106
Park, J. W. ..........................................................168
Parnas, J. ............................................................154
Parzer, P. ..............................................................75
Pascual, J. C. ......................................167, 199, 213
Paskova, B. ............................................78, 88, 161
Patel, V. 71, ..................................88, 92, 121, 169
Patrycja, S. ..........................................................82
Pavelic, J. ..............................................................67
Pavlovic, E. ........................................................184
Pawezka, J. ........................................................154
Pedersen, R. ......................................................189
Pedrera, A. ..........................................................86
Peitl, V. ..............................................................154
Pekic, S. ............................................................152
Peles, E. ................................................................96
Pena, M. ....................................................157, 176
Penna, D. ..........................................................188
Penninx, B.W.J. .................................................... 80
Peplonska, B. ......................................................132
Perahia, D. ........................................................191
Peralta, V. ............................................................22
Pereira, A. ..........................................................152
Pereira, C. ..........................................................171
Pereira, J. ..........................................................107
Pereira, M. ................................................105, 216
Pereira, P. ..........................................................106
Perez, C. ............................................................176
Perez, V. ....................................................167, 199
Prez-Egea, R. ....................................................199
Perinot, L. ..................................................101, 102
Perlov, E. ............................................................179
Perna, G............................................................... 12
Perneczky, R. ........................................................72
Perren, S. ............................................................ 45
Pervomaysky, E. ....................................................98
Peternell, A. ........................................................60
Peterson, D. ........................................................67
Peterson, L. ..........................................................67
Petit-Demoulire, B. ............................................85
Petresco, S. ........................................................100
Petreski, D. ........................................................128
Petric, D. ............................................................147
Peuskens, J. ....................................................33, 47
Pezawas, L. ..........................................................83
Pfeffer, A. ..........................................................132
Pfuhlmann, B. ......................................................22
Philipsen, A. ......................................................179
Phillips, M. ........................................................178
Picchietti, M. ..............................................119, 214
Piccinni, A. ........................................................ 110
Pichkhadze, G. ..................................................215
Pilarz, Z. ....................................................118, 205
Pilc, A. ..................................................................50
Pilowsky, D. ........................................................192
Pinder, R. ..............................................................74
Pinheiro, C. ........................................................197
Pinheiro, S. ........................................................199
Pires, Z. ......................................................105, 216
Piszczek, R. ........................................................154
Pivac, N. ..................................63, 67, 89, 116, 127
Plotkin, M. ........................................................175
Pogosyan, A................................................. 92, 106
Pokan, R. ..............................................................88
Polazarevska, M. ................................................191
Poletti, G. ..........................................................217
Pollack, M. ........................................................114
Popovic, S. ........................................................184
Popovic, V. ........................................................152
Portala, K. ..........................................................116
Porto da Nobrega, L. ..........................................138
Potkin, S. G. ................................................83, 144
Povo Canut, A. ..................................................203
Powell, J. ............................................................155
Power, A. E. ........................................................12
Pozzoli, S. ......................................................27, 52
Prasko, J. ......................................78, 88, 161, 162
Prause, W. ............................................................45
Pregelj, P. ..............................................72, 90, 167
Presecki, P. ..........................................................127
Pridmore, S. ......................................................216
Prieto, M. ..........................................................204
Prikryl, R. ..............................................................30
Primus, G. ..........................................................129
Prince, M. ............................................................19
Prins, J. ..............................................................207
Przybylo, J. ................................................118, 205
Psiquis, M. ..........................................................173
Puigdemont, D. ..................................................199
Pumarino, L. ..............................................166, 197
Pungercic, G. ......................................................167
Q
Quadrelli, B. ........................................................36
Quail, D. ............................................................191
Quevedo, Y. ......................................................103
Quijada, M. ........................................................155
Quilty, L.C. ........................................................111
Quintanilla, E. ............................................202, 216
Qusar, S. ..............................................................90
R
Radut, C. ............................................................115
Rainer, M. ............................................................85
Raju, T. R. ....................................................86, 163
Raju, T.R. ............................................................109
Rakitina, N. ..................................................92, 183
Ramakrishna, K. K. ..............................................86
Rambu, A. ............................................................76
Ramesh, D. J. ....................................................141
Ramirez, L. ..........................................................54
Ramon, F. ..........................................................207
Rangel, N. ............................................................76
Rao, G. P. ............................................................58
Rao, R. .............................................................. 140
Raouf, A............................................................... 70
Rappard, F. ........................................................141
Raskin, J. ............................................................190
Rasmussen, K. ....................................................191
Ratzke, O. ..........................................................195
Ravishankar, S. ..................................................141
Razzouk, D. ........................................................217
Recchia, L. ..........................................................219
Rees, H. ........................................................94, 95
Reisecker, F. ........................................................174
Reisinger, K. ......................................128, 133, 183
Renou, J. ................................................................7
Resta, F. ................................................................52
Retamal, P. ........................................................103
Rex, A. ..............................................117, 133, 171
Reynolds, R. ......................................................141
Ribeiro Jr, F. ................................................125, 206
Ribordy, F. ..........................................................206
Rickels, K. ..........................................................197
Riedel, M. ............................................................32
Riemann, D. ..................................................11, 12
Riepe, M. ..........................................................131
Rihova, Z. ..........................................................133
Risco, L. ................................................................10
Ritvo, A. ..............................................................37
Rivera, G. ....................................................60, 114
Rivera-Antongiorgi, N. ........................................175
Riveros, M. ........................................................212
Rizos, E. ............................................................145
Roa, N. ......................................................166, 197
Robert, P. ..........................................................128
Roberta, B. ........................................................181
Rocamora, R. ................................................45, 73
Rocca, C. ............................................................100
Rodriguez Garin, E. ..............................................40
Rodrguez, A. ....................................................135
Rodriguez-Martos, T. ..........................................137
Rohrmeister, K. ....................................................60
Rojas, G. ....................................106, 176, 182, 192
Rojas, M. ............................................................216
Rojas, P. ......................................................106, 182
Rojas, R. ....................................................106, 182
Rojnic Kuzman, M. ............................................141
Rojo Moreno, L. ................................................203
Roland, C. ............................................................ 60
Romanelli, R. ........................................................93
Romeo, F. ..........................................................187
Romero, L. ........................................................172
Roncaglia, I. ......................................................110
Rosa, P. ..............................................................117
Rosanova, M. ......................................................52
Rosrio, M. C. do ..............................................215
Rosenthal, C. ......................................................198
Rossi Menezes, P. ................................................ 42
Rotella, F. ..........................................................119
Rothe, J. ............................................................133
Rothhammer, F. ..................................................167
Rouillard, C. ......................................................142
Rouleau, G. A. ....................................................37
Rovner, J. ..................................................185, 202
Rozanov, V. .......................................................... 81
Rubesa, G. ........................................................218
Rubio Granero, T. ..............................................203
Rudalevicienne, P. ..............................................159
Rueda Jaimes, G. E. ....................................122, 124
Ruiz, A. ..............................................................155
Ruiz, I. ................................................................135
Ruiz, J. C. ..........................................................148
Rupprecht, R. ....................................................104
Russel, J. ............................................................113
Russo, S. ..............................................................80
Rybakowski, J. ..............................................38, 130
Rynn, M. ............................................................113
S
Sacchetti, E. ......................................................187
Sacher, J. ..............................................................42
Saferstein, D. ......................................................179
Safiullina, V. ........................................................94
Sagar, R. ............................................................148
Sagastegui, A. ....................................................217
Sager, T. .............................................................. 97
Saghafi, M. ..........................................................72
Sagud, M. ............................................................63
Sain, I. ................................................................151
Saito, H. ............................................................151
Saiz, D. ..............................................................168
Saiz-Ruiz, J. ..................................................86, 168
Sajatovic, M. ........................................................53
Salamero Baro, M. ..............................................211
Salas, A. ......................................................19, 188
Salazar, I. ............................................................217
Salcic, D. ............................................................184
Saletu, B. ....................................................45, 174
Saletu-Zyhlarz, G. ................................................45
Salomon, S. ................................................163, 166
Sambati Oliva, V. H. ............................................195
Sampaio, T. ........................................................197
San Martin, L. ....................................................168
Sanches, T. ........................................................176
Sanchez Pedraza, R. ..........................................100
Sanchez, J. ........................................................188
Sanchez-Russi, C. ..............................................140
Sander, K. ............................................................82
Santelia, S. ........................................................153
229
AUTHOR INDEX
Santos, A. C. ......................................................143
Santos, V. dos ............................................127, 156
Sarabia, S. .......................................................... 217
Sari, M. ................................................................89
Saric, M. ......................................................91, 116
Sathyaprabha, T. N. ..............................86, 109, 163
Sato, M. ..............................................................26
Savas, H. ............................................................215
Savolainen, P. ....................................................164
Saxon, A. ............................................................97
Scandurra, V......................................................... 69
Scapola, M. ................................................101, 102
Scarpato, A. ......................................................119
Scazufca, M. ........................................................42
Schacky, C. von ..................................................104
Schfer, M. ........................................................138
Schall, U. ............................................................123
Scharl, T. ............................................................166
Schastnyy, E. ......................................................211
Schaufelberger, M. ..............................................42
Scheen, A. ............................................................47
Schewe, H.-J. ....................................................131
Schiavi, E. ..........................................................110
Schiltz, K. ............................................................ 78
Schloegelhofer, M. ............................135, 138, 166
Schmahl, C. ..........................................................54
Schmidt, L. G. ....................................................177
Schmidt, L.C. ......................................................130
Schneider, F. ........................................................43
Schnellenkamp, K. ................................................95
Schneyer, T. ........................................................118
Schoeggl, H. ..............................................173, 183
Schoeman, R. ....................................................118
Schoenknecht, P. ....................................72, 73, 127
Schosser, A. ........................................................166
Schreiber, M. ......................................................195
Schreiber, S. ........................................................96
Schroeder, J. ..........................72, 73, 127, 156, 174
Schuele, C. ........................................................104
Schwalen, S. ......................................................131
Schwartz, D. ..............................................108, 119
Schwarz, M. J. ................................................32, 33
Scott, L. V. ..................................................208, 209
Scully, P. ....................................................208, 209
Seedat, S. ....................................................49, 118
Segal, Z.V. ..........................................................111
Seidl, U. ............................................................127
Selek, S. ............................................................215
Selim, O. ..............................................................69
Semke, A. ..........................................................150
Semke, V. ..........................................................213
Seres, J. ..............................................................210
Seres, P. ..............................................................210
Serfaty, E. ............................................................17
Serrano Garcia, A. ..............................................219
Serrano, A. ..........................................................76
Seung-Keun, W. ................................................139
Sevaljevic, N. ......................................................160
Shah, N. ............................................................136
Shahid, M. ........................................101, 143, 144
Shaikh, M. ..........................................................218
Sham, P. ............................................................155
Sharma, T. ............................................................37
Sheehan, D. ......................................................197
Shein, P. ............................................................208
Shekhar, A. ........................................................197
Shih-Tsung, C. ....................................................114
Shim, S. ..............................................................191
Shin, C. K. ..........................................................137
Shin, Y.-K. ..........................................................210
Shlik, J. ................................................................14
Shoji, Y. ..............................................................157
Shou, S.-F. ..........................................................143
Shrivastava, A. ..........................................136, 200
Shy, M.-J. ..........................................................149
Si, T. ....................................................................48
Sieghart, W. ......................................................166
Sierra SanMiguel, P. ............................................203
Siessmeier, T. ........................................................83
Siever, L. ........................................................15, 55
Silk, K. ..................................................................59
Silva, A. ..............................................................152
230
Silva, H. ..............................56, 166, 182, 197, 204

Silva, H. I. ..........................................................202
Silva, V. ..............................................................159
Simal, P. ..............................................................86
Simhandl, C. ........................................................87
Simon, N. ..........................................................114
Simonic, A. ........................................................195
Simsek, E. ..........................................................108
Simsek, Y. ..........................................................108
Simutkin, G. ..............................................183, 190
Singh, K. ............................................................ 113
Singh, R. A. ........................................................200
Singleton, A. ......................................................168
Sinke, R. ..............................................................76
Skibinska, M. ........................................................38
Skolnick, P. ..........................................................50
Skrdlantova, L. ....................................................78
Slachevsky, A. ............................................157, 176
Smekal, G. ..........................................................88
Smit, G. ................................................................80
Smit, J. ................................................................80
Soares, O.T. ........................................................109
Sokolowski, M. .................................................... 81
Sokolska, E. ........................................................154
Solari, A. ....................................................166, 197
Soler, C. ............................................................219
Soler, J. ......................................................167, 199
Soler, M. J. ........................................................148
Solis, J. ..............................................................192
Sommer, T. ........................................................175
Soncini, J. ..........................................................188
Song, C. ......................................................31, 132
Sooampon, S. ....................................................192
Sorensen, G. ........................................................97
Sos, P. ................................................................162
Sosa Ortiz, A. L. ..................................................19
Souza, C. ............................................................69
Souza Duran, F. L. de ..........................................42
Soyoung, L. ........................................................196
Spahic-Mihajlovic, A. ............................................67
Spaniel, F. ..........................................................149
Sperner-Unterweger, B. ........................................23
Spijker, S. ............................................................80
Spindelegger, C. ..............42, 82, 84, 117, 176, 177
Stachowicz, M. ....................................................87
Stadelmann, S. ....................................................45
Stadlin, A. ..........................................................206
Starcevic, V. ..........................................................87
Stefanescu, C. ..........................................96, 97, 99
Stefanovski, B. ....................................................191
Stein, D. ............................................................114
Stein, M. ............................................................123
Stein, P. ........................................84, 117, 176, 177
Stern, H. ..............................................................83
Sticht, M. ..........................................................205
Stber, G. ............................................................23
Stoeter, P. ..........................................................177
Stravogiannis, A. ................................................103
Strejilevich, S. ............................................101, 102
Strele, A. ............................................................129
Strik Lievers, L. ....................................................80
Strik, W. ..............................................................44
Strnad, A. ....................................................75, 159
Strom, B. ............................................................141
Strukelj, K. B. ....................................................106
Strunzova, V. ......................................................164
Stuchlik, A. ........................................................186
Styczynska, M. ..................................................132
Su, T.-P. ........................................................86, 158
Subhani, A. U. Haq ..............................................73
Subhani, F. U. Haq ................................................73
Subramaniam, K. ....................71, 88, 92, 121, 169
Suckling, J. ........................................................171
Suh, S. ..............................................................209
Suhara, T. ............................................................41
Sukiasyan, S. ................................................ 92, 106
Suljic, E. ............................................................214
Sumiyoshi, T. ........................................................31
Sumner, B. E. H. ................................................143
Sun, H. .............................................................. 145
Sun, X. ................................................................37
Sun-Woo, L. ......................................................139
Sushko, V. ..........................................................203
Suzuki, M. ............................................................31
Svesko-Visentin, H. ............................................218
Sweeney, J. ..........................................................82
Szajer, K. ............................................................154
Szmycinska, E. ....................................................154
Szymona, K. ......................................................154
T
Taanila, A. ......................................................75, 77
Tai, K.S. ..............................................................171
Taler, M. ............................................................182
Tamas, Z. ..............................................................70
Tammelin, T. ........................................................77
Tan, H. ..............................................................185
Tan, W. ..............................................................185
Tandon, R. ..........................................................200
Tang, S. W. ..................................................64, 192
Taparel, S. ..........................................................206
Tapia, B. ............................................................212
Tapia, G. ............................................................105
Tapp, A. ..............................................................97
Taranath Shetty, K. ............................................146
Tarazi, F. ............................................................158
Taso, C.-H. ........................................................143
Tauscher, J. ..........................................................42
Tavares, H. ................................................178, 215
Tavcar, R. ....................................................140, 193
Taya, S...................................................................21
Tazakori, Z. ........................................................217
Tebartz van Elst, L. ..............................................179
Tedeschi, D. ..........................................................93
Tempelmann, C. ..................................................78
Terovsky, S. ..........................................................94
Terribilli, D. ........................................................179
Thakar, M. ..........................................................136
Thase, M. ..........................................................189
Thau, K. ..............................................................60
Thibaut, F. ......................................................39, 53
Thirthalli, J. ..................................86, 109, 146, 163
Thomann, P. ......................................127, 156, 174
Thomas, R. ..........................................................67
Thum, A. ................................................45, 73, 118
Tiana, T. ....................................................167, 199
Tic-Bacic, T. ........................................................218
Tislerova, B. ........................................................161
Tisseron, A. ........................................................136
Tiugan, A. ..........................................................115
Toledo, V. ..........................................................121
Toloza, P. ............................................................104
Tomas, P. ............................................................148
Tomcuk, A. ........................................................160
Tomczak, A. A. ..........................................111, 207
Tomori, M. ..................................................90, 167
Tondo, L. ..............................................................17
Topic, R. ................................................67, 91, 116
Topkova, P. ........................................................172
Toro, P. ............................65, 72, 73, 127, 156, 174
Torregrosa, X. ....................................................212
Torres, A. ............................................................215
Tottrup Brennum, L. ............................................97
Trabattoni, D. ......................................................27
Trabulo, C. ........................................................107
Trimble, M. ..........................................................36
Tripathi, B. M. ....................................................148
Trivedi, J. ............................................................104
Trivedi, J. K. ........................................................200
Trujillo, F. ............................................................137
Trzepacz, P. ........................................................214
Tsai, F.-Y. ............................................................200
Tsakanova, G.V. ..................................................148
Tsang, J.T.K. ........................................................171
Tschacher, W. ......................................................82
Tuinier, S. ..........................................................218
Tummala, R. ......................................................114
Turecki, G. ......................................................37, 38
Turner, J. ..............................................................83
Turner, N. ..............................................................9
Turyanov, T. ........................................................142
U
Ubilla, J. ............................................................119
AUTHOR INDEX
Udupa, K. ............................................86, 109, 163

Uebelhack, K. ....................................................175
Uebelhack, R. ............................................131, 175
Ueno, M. ............................................................151
Ulla, M. ..............................................................126
Urban, A. ..........................................133, 156, 174
Urbanova, E. ......................................................133
Urbanska, A. ......................................................154
Ustundag, B. ......................................................185
Uzcategui, E. ........................................................76
Uzcategui, M. C. ..................................................76
Uzun, S. ............................................................201
V
Vacarezza, A. ............................................104, 119
Vaithiyam, A. ......................................................186
Valdebenito, M. ....................................................95
Valdivia, M. ................................................168, 220
Valent, M. ..........................................................62
Vales, K. ............................................................186
Valesova-Bubenikova, V. ....................................205
Valim, A. C. ........................................................103
Valinurov, R. ......................................................142
Valis, M. ....................................................133, 174
Vallada, H. ................................................103, 176
Vanderburg, D. ..................................................187
Vanderhasselt, M.-A. ......................................78, 79
Vanegas, C. ................................................136, 217
Vargas, A. ..........................................................105
Vargas, D. ............................................................76
Vasilyeva, S. ........................................................190
Vaswani, M. ......................................................140
Vavrusova, L. ........................................................30
Vaz de Lima, M. ................................................132
Vazquez, J. L. ....................................................105
Vega, R. de la ....................................................112
Vega, S. ..............................................................208
Veijola, J. ........................................................75, 77
Velligan, D. ........................................................159
Venizelos, N. ................................................25, 151
Venkatasubramanian, G. ....................................146
Ventura, T. ..........................................................219
Verhoeven, W. M. A. ..........................................218
Vernaleken, I. ......................................................83
Vetlugina, T. ......................................................142
Vetro, A. ........................................................65, 70
Vidal Hagemeijer, A. ..........................................211
Videla, C. ..........................................................212
Videnova, V. ......................................................191
Videtic, A. ..........................................................167
Vielma, W. ........................................................197
Vieta, E. ..............................................................62
Villano, L. A. ......................................................212
Villarroel, J. ................................................166, 197
Vinci, C. ............................................................171
Vitezic, D. ..........................................................195
Vitriol, V. ............................................108, 119, 120
Vladut, V. ..........................................................147
Voderholzer, U. ..............................................12, 85
Vhringer, P. ......................................................155
Vohs, K. ............................................................131
Voigt, J.-P. ..................................................117, 133
Votava, M. ................................................199, 202
Vucic Peitl, M. ....................................................154
Vucurevic, G. ......................................................177
Vue, C. ..............................................................142
Vujovic, V. ..........................................................191
Vuksan, B. ............................................................89
Vuksan-Cusa, B. ................................................132
Vumma, R. ........................................................151
Vyssoki, D. ........................................................116
W
Wada, Y. ..............................................................98
Wadsak, W. ................................................117, 176
Wagner, G. ........................................................125
Wahl, K. ..............................................................85
Wampers, M. ......................................................47
Wan, V. L. ..........................................................206
Wang, J.-F. ..........................................................37
Wang, L. ............................................................141
Wang, S.-J. ..........................................................86
Wanner, C. ........................................................125
Warrington, L. ....................................................187
Wasiak, B. ..........................................................132
Wasserman, D. ....................................................81
Wasserman, J. ......................................................81
Weickert, C. S. ....................................................21
Weil, K. ..............................................................120
Weinberger, D. ............................................83, 148
Weiner, I. ..............................................................24
Weinstock, M. ............................................163, 166
Weizman, A. ......................................................182
Weizman, R. ......................................................182
Werneck-Rohrer, S. ............................................135
West, T. ..............................................................202
Wheeler, A. ........................................................139
Whitty, A. ............................................................96
Wiebking, C. ........................................................78
Wiesel, F.-A. ................................................25, 151
Wigg, K. ........................................................65, 70
Wildt, B. T. e. ....................................................196
Willeit, M. ............................................................42
William, J. ..........................................................207
Williams, S. ........................................................139
Willis, P. ..............................................................184
Wilner, K. ..........................................................188
Wilson, J. ..........................................................135
Windischberger, C. ................................82, 84, 177
Winklbaur, B. ......................................................60
Winkler, D. ........................................................182
Wistel, A. ..........................................................133
Witkin, J. ..............................................................50
Wittgens, W. ......................................................195
Witzel, J. ..............................................................78
Wber, C. ..........................................................125
Wber-Bingl, C. ................................................125
Woldbye, D. ........................................................97
Wollenberg, J. ......................................................91
Wlwer, W. ..........................................................28
Wong, E. H. F. ....................................101, 143, 144
Wong, E. Y. Chun ..............................................193
Wong, J.C.H. ......................................................171
Wong, M. ....................................................49, 192
Wong, M.-L. ........................................................46
Wongwitdecha, N. ......................84, 115, 192, 198
Woo, Y. S. ..........................................................169
Woo, Y.-J. ..........................................................137
Wood, A. ............................................................97
Woodruff, P. W. ....................................................43
Wrtwein, G. ..............................................97, 165
Wu, E. C.-Hsuan ................................................200
Wu, Y.-l. ............................................................148
Wbbena, T. ......................................................118
Wyl, A. von ........................................................45
Z
Zalesky, R. ....................................................78, 161
Zamora Cabral, R. T. ..........................................161
Zamora, S. ................................................108, 202
Zamorano, C. ....................................................106
Zanarini, M. ..........................................................54
Zangrossi, H. ......................................................199
Zanoni, S. ..........................................................181
Zanten, J. van ......................................................80
Zarra, J. ......................................................130, 202
Zawertailo, L. ....................................................7, 8
Zegers, G. ..........................................................168
Zesch, H.E. ........................................................125
Zhang, X. ............................................................27
Zhou, B. ............................................................148
Zhvania, M. ........................................................162
Ziegenbein, M. ..................................................196
Zierhut, K. ............................................................78
Ziolkowska-Kochan, M. ......................................130
Zivin, M. ..............................................................72
Zohar, J. ..............................................................14
Zormann, A. ......................................................125
Zuardi, A. ..........................................................143
Zubieta, J. ............................................................59
Zuin, D. R. ..........................................................219
Zullino, D. F. ......................................................206
Zumrova, A. ......................................................133
Zung, S. ....................................................103, 176
Zuniga, C. ..........................................................104
Zupan, G. ..........................................................195
Zupanc, T. ..........................................................167
Zurowski, B. ........................................................85
Y
Yacubian, J. ........................................................175
Yadav, V. S. ........................................................200
Yaka, R. ..............................................................163
Yamamoto, H. ....................................................157
Yamilet, I. ..........................................................172
Yan, B. ......................................................189, 190
Yang, B.-H. ..........................................................86
Yang, M.-J. ........................................................114
Yang, R. ............................................................187
Yangrae, K. ........................................................196
Yao, J. ..................................................................24
Yao, L. ..................................................................98
Yashavantha, B. S. ..............................................141
Yasseen, B. ............................................................7
Yee, B. K. ..........................................................153
Yehuda, R. ..........................................................16
Yetkin, S. ..............................................................65
Yilmaz, H. R. ......................................................215
Yip, L. ................................................................171
Ylstra, B. ..............................................................80
Yolken, R.H. ........................................................32
Young, L. T. ..........................................................37
Young, T. ..............................................................38
Yu, C. Y. ............................................................148
Yu, P. ..................................................................185
Yuce, M. ............................................................215
Yunez, R. ............................................................140
231
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The World Journal

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The World Journal of Biological Psychiatry, Supplement 1, Vol 8, 2007

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T2 Affective Disorders (Bipolar)

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illness, cycloid psychoses, unsystematic schizophrenias and systematic

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