Autistic Spectrum Disorders:

AKA PDD

James H. Johnson, Ph.D., ABPP

University of Florida
Pervasive Developmental Disorders:
Old and New Labels
• The current DSM IV category of Pervasive
Developmental Disorders includes several more severe
forms of child psychopathology.
• Historically disorders of this type have been referred to
by a variety of labels such as
– atypical psychosis,
– child psychosis,
– symbiotic psychosis,
– childhood schizophrenia, and
– infantile autism
 Evolution in the Classification of
PDD
• Prior to 1980 and the development of DSM III. there
was no adequate classification system for the diagnosis
of these disorders.
• In DSM II there was no category appropriate for more
severe forms of child psychopathology apart from
“Childhood Schizophrenia”.
• This category was very general and not sufficient for
the diagnosis of the full range problems now
considered under the heading of PDD
 DSM II Criteria for Childhood
Schizophrenia
• Symptoms appear before puberty.
• The conditions may be manifested by autistic, atypical
and withdrawn behavior;
• Failure to develop an identity apart from the mothers
with general unevenness, gross immaturity, and
inadequacy of development.
• These developmental defects may result in mental
retardation, which should also be diagnosed.
• Although some children met criteria for this disorder
most with severe psychological problems did not.
DSM III: A New Category for PDD
• In DSM III an attempt was made to provide
more adequate diagnostic categories for
classifying more serious forms of child
psychopathology.
• Here two primary diagnostic categories
were provided, as were more objective
diagnostic criteria and specific decision
rules for making diagnoses.
PDD: General Characteristics of the
Category
• Pervasive Developmental Disorders considered within DSM IV differ
in a variety of ways
– severity of impairment,
– age of onset,
– likely etiological factors involved
• They are similar in reflecting core features that define the general
diagnostic category.
• They are seen as disorders characterized by pervasive impairments in
several areas, including;
– deficits in reciprocal social interactions,
– deficits in communication skills, and
– the presence of stereotyped behaviors/interests/activities
Developmental - Yes; Psychotic - No
• At one time, conditions now referred to as Pervasive
Developmental Disorders were thought to be reflective
of Child Psychosis.
• As these disorders generally bear little relationship to
the psychotic conditions of adulthood (e.g.
Schizophrenia, Bipolar Disorder), they are now
referred to as "developmental" rather than "psychotic"
disorders.
 “Pervasive” vs “Specific”
Developmental Disorders
• These "pervasive" developmental disorders are to be
distinguished from "Specific Developmental Disorders"
(e.g., reading, articulation, arithmetic, and language
disorders).
• This is because they are characterized by severe
disturbances in many basic areas of development.
• They may also be reflected in behaviors  having no
counterpart in normal development.
• Children with these conditions often display distorted
rather than simply delayed development.
 DSM III: the Original PDD
Classification
• In the initial development of DSM (DSM III), only
three categories of Pervasive Developmental
Disorders were included;
– Autism
– Childhood Onset Pervasive Development Disorders.
• There was also a more general category of “Atypical
Pervasive Developmental Disorder” that could be
used for children not diagnosable, using criteria for
the other two categories.
 DSM III: Autism Criteria
• Onset before 30 months
• Pervasive lack of responsiveness to other people
• Gross deficits in language development
• If speech present, peculiar speech patterns
(e.g.echolalia, pronoun reversal)
• Bizarre responses to various aspects of the environment
– resistance to change; peculiar interests in or
attachment to animate or inanimate objects.
We will discuss Autism in more detail later.
DSM III: Childhood Onset PDD
Diagnostic Criteria
• A profound disturbance in social
relationships and multiple oddities, all
developing after 30 months of age and before
12 years (to separate it from Autism and Schizophrenia).
• The disturbance in social relationships is
gross and sustained, with such symptoms as
lack of appropriate affective responses,
inappropriate clinging, asocial behavior and
lack of peer relationships.
 DSM III: Childhood Onset PDD
Diagnostic Criteria – cont.
• Oddities of behavior include;
– Sudden excessive anxiety
– Constricted or inappropriate affect
– Resistance to change in the environment
– Insistence on sameness
– Oddities in motor movement
– Speech abnormalities
– Hyper or hypo-sensitivity to sensory stimuli and
– Self mutilation
 Childhood Onset PDD:
Associated Features
• Bizarre ideas and fantasies and preoccupation with
morbid thoughts and interests.
• Pathological preoccupation with, and attachment
to, objects such as always carrying a string, rubber
band, straw, etc.
• While seemingly representing an advance in
attempting to be more objective in making
diagnostic judgments, this classification approach
changed in 1987 with DSM III –R.
 PDD and DSM III – R: Moving
Forward or Backward
• In DSM III – R this category was changed
dramatically.
• The Childhood onset PDD category was
eliminated.
• Only the category of Autism was retained with this
nature of the autism criteria being modified in
several ways including;
– Removing the age-of-onset criterion
– Broadening the autism criteria thus distorting the
traditional conceptualization of autism.
 PDD and DSM III – R: Moving
Forward or Backward – cont.
• This broadening of the autism criteria came at a time
when research was suggesting that it was important to
start looking at subtypes of autism.
• The changes resulted in many cases, that would have
been diagnosed as COPDD being classified as autism.
• Research suggested that diagnoses using these new
criteria
– Did not correspond to DSM III diagnoses of Autism or
– Relate closely to clinician views of autism.
• This prompted major changes in the PDD system.
– Modifications were made for DSM IV.
– DSM IV is more similar to DSM III than DSM III-R!
 DSM IV: Current PDD Disorders
• Several disorders are included under the present
day DSM IV heading of Pervasive Developmental
Disorders.
– Asperger's Disorder
– Autistic Disorder
– Rett Disorder
– Childhood Disintegrative Disorder
– PDD (NOS)
– Asperger’s Disorder, Autism, and PDD (NOS) are
frequently also referred to as Autistic Spectrum
Disorders (Gillis & Romanczyk, 2008)
 Asperger's Disorder: The Least
Severe of the Severe Disorders
• The first published account of this disorder was by
Austrian psychiatrist Hans Asperger in 1944 who initially
referred to the condition as "autistic psychopathy".
• It is interesting to note that Dr. Asperger’s own
preoccupations, interests and social aloofness suggest that
he may himself have had an autistic spectrum disorder
(Lyons & Fitzgerald, 2007)
• Asperger used the term "autistic" in the technical sense to
refer to an abnormality of personality rather than features
of infantile autism.
• However, more recent authors have commented on the
similarities between these disorders.
• Indeed, there is some debate as to whether this disorder is
actually distinct from autistic disorder.
 Essential Features
• Essential features include
– severe impairments in social interactions
– restricted and repetitive patterns of interests, activities and/or
behaviors
– that result in impairment.
• No clinically significant delays in cognitive development,
language development
• While not a specific symptom of Asperger's Disorder, children
with this condition are often delayed in meeting major motor
milestones (e.g., crawling, walking) and are frequently
characterized as clumsy.
 Asperger’s: Social Impairments

• In autism, social impairments seem to result

from an intense desire to avoid social
interactions.
• The social impairment in Asperger’s seems to
result more from a lack of social skills and lack
of social perspective taking.
• These children seem to have a marked inability
to understand and use rules which typically
guide social behavior.
 Asperger’s: Social Impairments
• The child with Asperger’s may show
significant problems with;
– nonverbal behaviors such as maintaining
appropriate physical proximity to others while
interacting,
– making and sustaining eye contact, and
– appropriately using gestures, facial expression
and other nonverbal behaviors to regulate social
interactions.
Egocentricity of Social Behaviors
• Social behavior often appears egocentric and self-
centered,
• Here, the child may frequently pursue his/her own
highly personalized interests in social encounters
without apparent awareness that the other person
does not share similar interests.
• Behavior occurring within the context of two way
social interactions often appears as inept, naive and
peculiar.
 Restricted/Repetitive Behaviors
• Restricted and repetitive patterns of behaviors,
interests, or activities are often striking and may be
manifest in a variety of ways.
• Some may be preoccupied with specific activities
(e.g., spinning objects) or become overly attached to
certain objects or familiar places and become
intensely upset when separated from them.
• Others show an inflexible adherence to daily
routines.
 Restrictive Patterns of Interest
• Children with this disorder often show an extreme all-
consuming involvement in some specific area of
interest.
– The child may spend most of his/her time learning facts
related to the area.
– They may collect things having to do with the area, and
spend an enormous amount of time talking to others about
this area whether or not they are interested.
– While, investing a great deal of time learning about their
area of interest, the child may have little understanding of
the facts that they learn
– This results in significant impairment.
 Aperger’s vs Autism
• Unlike other PDD’s, in Asperger's Disorder, there is no clinically
significant delay in cognitive development or language.
• The child may learn to speak at a normal age and typically
acquires a command of grammar (Children with autism have problems with
this).
• They may, however, show marked peculiarities in language.
• They may invent words, use pronouns incorrectly, or repeat
words or phrases over and over in a stereotyped manner.
• These children are often extremely concrete and literal with a
poor understanding of sarcasm or irony (Wiznitzer (2009).
• May have big problem with idioms.
• The content of speech is often overly pedantic, often consisting
of long one-sided discussions about the child's favorite topic.
 Asperger’s vs. High Functioning Autism

• Is Asperger’s disorder is a separate disorder or just a variant

of autism in higher functioning individuals.
• Some evidence suggests that children with Asperger’s and
high functioning autism are more alike than different and that
Asperger’s may simply be a variant of autism (Frith, 2004).
• However, children with Asperger’s and high functioning
autism seem to show distinct patterns of social impairment
with
– children with Asperger’s being rated as “socially active but odd”
and
– those with autism rated as “aloof and passive” (Ghaziuddin, 2008)
 Epidemiology
• While there is little good data regarding prevalence,
children meeting criteria for Asperger's Disorder are
quite rare.
• In a total population study of children between ages 7-
16 in Goteborg, Sweden the minimum prevalence of
Asperger's Disorder was found to be 36/10,000. 
• The disorder appears more common in males than in
females.
• Sex ratios ranging from 3.75 : 1 to 9:1 are reported.
 Asperger’s: Etiology
• Regarding etiology, the disorder was originally
considered to have a genetic basis (Asperger, 1944).
• While no formal studies firmly documenting a genetic
etiology have been published, case study findings are
available.
• For example, in an early study Wing (1981) found that,
of the 34 cases with this disorder that she studied, 5 of
the 16 fathers and 2 of the 24 mothers had, "to a marked
degree" behavior resembling that observed in their
children.
 Asperger’s: Etiology
• Providing tentative support for some sort of biological etiology,
Wing (1981) found that almost half of the 34 cases she studied
had a history of pre-, peri-, or post-natal complications (e.g.,
anoxia) sufficient to cause neurological impairment.
• Although not definitive, support for the role of biological factors
comes from the fact that these children sometimes often show
evidence of nonspecific neurological symptoms.
• Research findings have also suggested that children with
Asperger’s display abnormalities of the cerebellum and limbic
system that are not unlike those found in autism (Mash and
Wolfe 2007).
• More research will be necessary to determine the most
important contributors to this disorder.
 Asperger’s: Prognosis
• Given their higher level of functioning (due to a lack of basic
cognitive and language deficits) the prognosis is Asperger’s appears
much better than with other PDD’s.
• Early studies by Wing (1981) presented case reports of individuals
who were able to engage in gainful employment and function in a
simi-independent manner.
• A recent study found that 27% of those with Asperger’s had good
adult outcomes and 26 % had restricted or poor outcomes with a
very restricted life with no occupation and no friends (Mash and
Wolfe 2007)
• Obviously, prognosis is intimately related to treatment and
management approaches designed to deal with the child's
difficulties.
 Treatment of Asperger’s
• At present, no treatment has been shown to modify the
basic underlying impairment shown by children with
this condition,
• Behavioral approaches designed to enhance the child's
ability to function in social situations, along with an
educational program tailored to meet his or her specific
needs should be beneficial.
• Psychotherapy, while not likely to remediate the child's
basic difficulties, may be useful later on as the child
becomes aware of the degree to which social skills
limitations make it difficult to function without
experiencing personal distress.
Autism
• Infantile autism was first
described by Leo Kanner
(l943) in his classic paper
" Autistic Disturbances of
Affective Contact", which
was published in the, now
extinct journal, The
Nervous Child.
 Autistic Disorder
• In this seminal article, Kanner highlighted the
defining characteristics of 11 children seen in his
child psychiatry practice at Johns Hopkins
University.
• Kanner believed that these 11 children displayed
a type of disorder different from any that had
been described prior to that time.
• His views regarding this disorder have heavily
influenced present day views of the disorder,
emphasized a number of features
 Nature of the Disorder
• Unlike certain other severe disorders of childhood,
Kanner assumed autism to have an early onset.
• He believed the disorder to be present from the beginning
of life, or at least to become obvious during the first year
or so.
• Indeed, he referred to it as an "inborn disturbance".
• He felt that this early onset served to differentiate the
disorder from other problems, which at that time, were
judged to be manifestations of childhood psychosis.
 Defining Social Characteristics
• Autistic children have a primary disturbance in
social relationships and an apparent inability to
relate to others.
• They seem aloof, often oblivious to the presence of
others, and are often described as being in a world
of their own – “Like in a shell”, “Happiest when
left alone”, Acting as though people aren’t there”. .
• This may be reflected in early life by a failure to
show anticipatory posturing when the parent
attempts to pick them up from the crib, and the
failure of the infant to mold him or herself to the
body of the parent.
 Defining Social Characteristics
• Their problems in relating to others may be displayed by the
failure of the child to respond to parents or others.
• In some instances children may treat parents no differently
from others and may show almost no response when a
parent returns home, even after being gone for some time.
• Sometimes these children are thought to be deaf because of
their lack of responsiveness.
• This problem of emotional responsivity prompted Kanner to
describe the disorder as a primary disturbance of affective
contact.
 Social Aloofness as a Core Feature
• Kanner suggested that the outstanding fundamental
disorder is “the children’s inability to relate
themselves in the ordinary way to people and
situations from the beginning of life”
• He goes on to note that “this is not as in schizophrenic
children or adults, a departure from an initially present
relationships - it is not a “withdrawal” from formerly
existing participation.”
• There is from the start, an “extreme aloneness that
whenever possible disregards, ignores, shuts out
anything that comes to the child from the outside”.
 Autistic Language Impairments
• All autistic children show evidence of a severe
language disorder.
• Many remain mute.
• Those that develop speech typically show unusual
features such as echolalia (the repetition of what
someone else has said, just as it is said) or pronominal
reversal (failure to use pronouns correctly ‑ referring to
oneself as "you" and to others as "I").
• Even though some autistic children develop fairly large
vocabularies, they usually cannot use speech to
communicate with others.
 Autistic Language Impairments
• Kanner noted that although some of his 11 cases
developed language, they were no better able to
communicate than were those who remained mute.
• Speaking autistic children often have no difficulty in
naming objects and sometimes seem to have a facility for
learning previously constructed verbal materials such as
poems, songs, and lists of things.
• Such learning, however, seems to be without any
appreciation of the meaning of these materials.
• There is usually minimal evidence of spontaneous
speech that serves a communicative function
 The Desire for Sameness
• Kanner and others have noted that autistic children seem
to display an "anxious desire for the maintenance of
sameness.
• This refers to the fact that such children often get upset
when things in their environment are changed ‑ when
furniture is moved, when routines are changed, or when
toys the child has left in a particular position are moved.
• This may result in a catastrophic reaction lasting until
things are returned to their former state.
• This desire for sameness may lead some children to
display a wide range of ritualistic behaviors.
 Other Associated Features
• In addition to the characteristics suggested, by Kanner, other
behaviors are also found in some autistic children.
• Many autistic children show stereotyped behaviors.
• They may mouth objects, spend long periods of time flapping
their arms and hands, rock, or display other apparently
self‑stimulating behaviors.
• The may sometimes appear either under or over responsive to
environmental stimuli, or both.
• Sometimes this under responsiveness is reflected in an
apparent insensitivity to pain and in associated self‑injurious
behaviors.
 Prevalence of Autism
• Although autism has, from the beginning, been seen as a rare
disorder it has been difficult to determine its exact frequency of
occurrence.
• This is because investigators have often;
– used different criteria for diagnosis,
– because the disorder has frequently been confused with other severe
disorders of childhood, and
– because not all children with autism come to the attention of researchers.
• Prevalence data from early studies suggested very low rates of
occurrence, typically 4 or 5 cases per 10,000 children, and as
low as 2 per 10,000 for "classic" cases
 Prevalence of Autism
• A review of studies conducted since the mid 1980's has, however, suggested
higher prevalence figures.
• The few studies using DSM criteria have reported rates on the order of 10 per
10,000 (Classic Autism).

• Prevalence rates for Autism Spectrum Disorders

– Recently it has been suggested that somewhere between 1 in 500 to 1 in 166
children have an ASD! Center for Disease Control and Prevention (CDC)
– It is now being suggested that as many as 1 child per 150 (or more) may
have an autistic spectrum disorder (Yeargin-Allsopp et al , 2003)
– Other research has suggested that the prevalence for subtypes of autistic
spectrum disorder are approximately 22 per 10,000 for autism, 33 for 10,000
for pervasive Developmental disorder NOS, and10 per 10,000 for Asperger’s
disorder (Fombonne, et al , 2006)

• The disorder is more frequent in boys than in girls, with sex ratios ranging from
2.0 to 1 to 5.7 to 1.
 Autistic Success Stories
• In a classic paper entitled "How far can autistic
children go in matters of social adaptation?" Kanner
(l973) reported on a follow‑up of some 96 autistic
children seen prior to l953.
• Although the majority did not fare as well, 11 of the 96
achieved what he described as a favorable outcome.
• Here 3 obtained college degrees. Three went to junior
college. At time of follow-up one other was reported to
be doing well in college. The other four did not go
beyond high school or special education.
 Autistic Success Stories
• The occupations of these grown‑up autistics included
accountant, duplicating machine operator, lab technician,
bank teller, along with several other types of unskilled
work.
• Kanner noted that although these 11 children did show a
favorable outcome, none seemed to show any interest in the
opposite sex or marriage, suggesting continued problems in
close relationships.
• Kanner found outcome to be unrelated to having received
psychiatric treatment.
• The single best predictor seemed to be having useful speech
by age 5
 Prognosis of Autism
• In reviewing early follow‑up studies of autistic
children DeMyer, et al (1981) suggested that as many as
60 to 70 percent live a life of complete or
simi‑dependence, at home or in an institution.
• Only about 1 to 2 per‑cent seemed to have achieved
normal levels of independence, while others displayed a
borderline level of functioning.
• A better prognosis seemed to be associated with an IQ
greater than 60.
 Prognosis of Autism & Autistic
Spectrum Disorders
• Studies reviewed by Gillberg, et al (1992) suggest:
– Autism associated with severe mental retardation diagnosed
before age 5 carries a gloomy prognosis in respect of
psychosocial adaptation.
– Autism associated with mild mental retardation or near
average intelligence levels has a more variable prognosis.
– About half do poorly psychosocially in adulthood and do
not hold jobs or lead independent lives in other ways.
– However, a significant proportion of cases in this group has
a relatively favorable prognosis and can be self-supporting
as adults.
– Only a few are likely ever to be married or engage in
marriage-like relationships.
 Prognosis of Autism & Autistic
Spectrum Disorders
• In very high functioning cases with autism or
Asperger’s syndrome, the overall prognosis is
much better.
– Oddities of social style, communication and interests
are likely to remain, but some in this group hold down
jobs and many get married and have children.
– There is much less detail with regard to the outcome
picture in the high-functioning group than in the those
with concomitant mental retardation. Gilberg (1992).
 What about High Functioning
Autism
• Not a diagnostic category
• Term used in different ways
• Relates to those with autistic features but
who have higher level language skills and
may be normal in terms of cognitive
functioning
• Difficulties in distinguishing between this
and Asperger’s disorder.
 Etiology of Autism
• Views regarding the causes of autism can generally be
classified as psychogenic or biogenic in nature.
• Psychogenic theorists, citing early reports which
characterized the parents of autistic children as cold,
aloof, obsessional, refrigerator like, and in other less
than positive terms (see Kanner, l943), have emphasized
the role of parental variables in the development of
autism.
• Indeed, some clinicians such as Bettelheim (l967) have
suggested that negative maternal attitudes are of major
importance in the development of this disorder.
 Etiological Perspectives
• For the most part, research designed to link family variables to
autism has provided little support for psychogenic views.
• DeMyer, et al (1981) have noted that, in sharp contrast to early
portrayals of parents of autistic children as "refrigerator"
personalities, the last decade of investigation has found these
parents to be similar to those with children exhibiting other
severe childhood disturbances.
• "... Parents of autistic children have been found to display no
more signs of mental or emotional illness than parents of
children with organic disorders (with or without psychosis).
Failure of Psychogenic Explanations
• “In addition, they do not manifest extreme
personality traits such as coldness, obsessiveness,
social anxiety, or rage, nor do they possess
specific deficits in infant and child care (p.432)".
• As Gillberg (1990) has also emphatically noted
"there is no scientific evidence that psychological
or psychosocial stressors or circumstances can
lead to autism “(p. 110).
Etiology: A Biological Perspective
• There seems to be a growing conviction on the
part of most researchers and clinicians that
autism is a biologically based disorder.
• This point of view is supported by a wide range
of studies and findings that have in one way or
another implicated the role of biological factors.
• The specific biological factors that cause this
disorder have not been identified, although
several candidates have been identified.
 Biological Perspectives
• Autism has been shown to be related to biological
problems such as;
– the development of seizure disorders,
– abnormal EEG's,
– congenital infections (e.g,.rubella),
– chromosomal abnormalities,
– structural abnormalities of the left hemisphere,
– post mortem assessments
– genetic factors.
– retrolental fibroplasia
– minor physical anomalies
– congenitial syphillis
– neuropsychological findings
 Biological Findings in Autism:
Genetics
• Children with autism experience more health problems
during pregnancy, at birth or following birth than other
chidlren,
• Genetics : For identical twins the concordance rate for
autism is 60 to 90%; Concordance rates for fraternal
twins are near 0%.
• Overall heritability of autism approximately 80%.
• Family members of children with autism are also more
likely to display abnormal rates of social and language
problems like those seen in autism, but less severe.
 Biological Findings: Structural and
Functional Brain Imaging
• Abnormalities in the frontal lobes
• Structural abnormalities in the cerebellum and medial
temporal lobe and related limbic system structures.
• Cerebellum found to be significantly smaller than normal.
• Brain metabolism studies suggest decreased blood flow in
the frontal and temporal lobes
• Also decrease in functional interconnections between cortical
and subcortial regions and delayed maturation of the frontal
cortex
• Children with autism also display elevated levels of whole
blood seratonin.
 Causal Controversy
• Do Childhood Vaccinations cause autism?
• It has been suggested that Measles, Mumps, and
Rubella (MMR) vaccine can result in autism.
• There are some children, later diagnosed with autism,
who have initial language and social-communicative
behaviors disappear after getting vaccination.
• Here the vaccine itself has been implicated as has
thimerosal, a preservative used in this and other
vaccines.
• Available evidence does not support a link between
either and autism (Fombonne, 2008)
 Biological Perspectives
• Although methodological problems inherent in most
studies make it difficult to draw firm conclusions, taken
together these findings provide strong support for a
biogenic perspective.
• Indeed, after reviewing much of the literature related to
neurobiological factors in autism, Gillberg (1990) has
concluded that "autism is now regarded as a behaviorally
defined syndrome of neurological impairment with a wide
variety of underlying medical etiologies (p. 106)".
• Again, the specific biological factors most relevant to the
etiology of autism and their specific role remain to be
uncovered.
 Treatment of Autism
• Due to their severe cognitive and social impairments,
autistic children are unlikely to benefit from insight
oriented "talk therapies“.
• Although some authors have suggested that individual
psychotherapy can be of some value in working with a
small number of higher functioning autistic children.
• While there is presently no "cure" for autism,
behavioral approaches have achieved the most
obvious success.
 Operant Treatment of Autism
• Operant procedures, combined with modeling, have been
found useful in teaching language, as well as other socially
adaptive behaviors, and in decreasing many inappropriate
behaviors of autistic children which interfere with their
functioning.
• Despite these accomplishments, it must be noted that
bringing about such behavioral changes requires, not only
skills which very few clinicians possess, but also an
enormous amount of time.
• And, there is the problem of maintaining those treatment
gains that are made.
 Operant Treatment of
Autism
• That this approach can be worthwhile is suggested by the
results of a program run by Lovaas (1987).
• Here, children participated in an intensive, long-term,
treatment program that focused on imitation, language
development, the expression of appropriate emotions, and
appropriate play behaviors.
• Of the 19 children participating in the program, it was
possible to mainstream 8, and 7 were described as being
indistinguishable from normals.
• While the degree to which these children did in fact approach
normality has been questioned, the results clearly highlight
the potential contribution of behavioral treatments.
 Pharmacological Approaches
• Although much attention has been given to studying the usefulness of
pharmacological agents in the treatment of autism, some that were once
thought to hold a great deal of promise have turned out to be
disappointments.
• One such drug is fenfluramine.
• This drug was the subject of interest because it tends to reduce levels of
serotonin in the blood.
• Note that serotonin is one of the neurotransmitter that biochemical studies
have found to be elevated in some autistic children.
• Two preliminary studies in the 1980’s provided data suggesting that
fenfluramine reduces serotonin levels and brings about improvements in
functioning, as indexed by a social and intellectual indices .
 Pharmacological Approaches
• Results also suggested that when the treatment ceased behavior
deteoriated.
• Subsequently, other researchers have sought to evaluate the safety and
effectiveness of fenfluramine.
• These, investigations have not always found treatment effects to equal
those of prior studies.
• Indeed, they suggested that treatment effects often diminish after a few
months and that an increase in dosage had only a moderate impact on
symptoms.
• Despite early enthusiasm, most later controlled studies found no
consistent effects for fenfluramine.
• Further the association of fenfluramine with primary pulmonary
hypertension and (in combination with phentermine) valvular heart
disease has eliminated its use as a safe agent.
 Pharmacological Approaches
• Research with some drugs have shown them to be more
effective.
• For example, one drug (Haloperidol), which has been
used with adult schizophrenics and some other clinical
groups, has been shown to improve the learning ability
of autistic children and make them more responsive to
special education and behavior modification
• An especially noteworthy aspect of this treatment is
that therapeutic effects were obtained with lower doses
that do not seem to produce serious side effects
 Additional Drug Treatments
• A recent NIMH Multisite study (2005) has found newer,
atypical antipsychotic medications such as Risperdal® to be
useful in the treatment of autism.
• This medication, has been found to not only decrease
aggression but also reduced repetitive behaviors and increase
social interaction - all with limited side effects.
• The two-part study found that discontinuation after six months
prompted rapid return of the problem behaviors in most cases.
• Other drugs such as the SSRI’s may also be useful in
reducing repetitive behavior social avoidance in individuals
with autism.
• These seem to be more effective with adolescents with autism
as opposed to younger children.
• The use of other atypical antipsychotic drugs (e.g. Abilify) is
also being researched as well.
 Multimodal Treatments
• While behavior therapy and drug treatments have both shown
some promise in treating autism, there is research evidence to
suggest that treatment should not be an either/or proposition.
• For example, early research by Campbell, et al (1987) focused on
the efficacy of a combination of Haloperidol and behavior
modification in the treatment of 40 autistic children.
• The results of this study suggested that while haloperidol alone
was effective in reducing stereotyped behavior and withdrawal, a
combination of drug treatment and behavior therapy was
superior to either approach used in isolation.
• There is reason to believe that behavior modification in
combination with other newer drugs such as atypical anti-
psychotics would also be valuable.
 Multimodal Treatments
• These findings suggest that, rather than looking
for one specific form of treatment to deal with the
diverse symptoms of autism (which may be a
diverse disorder), it may be important to employ
multimodal treatments that are designed to bring
about specific types of treatment effects.
• And, the importance of special education in the
child’s treatment should not be minimized
 Living with Autism:
Temple Grandin, Ph.D
» http://www.npr.org/templates/story/story.
php?storyId=4278538
 Rett Disorder
• This disorder, first described in 1964 by Dr.
Andreas Rett
• Did not receive worldwide recognition until
English language publication by Dr. Bengt
Hagberg in 1983
• It is a neurodevelopmental disorder which is
manifest in both physical & behavioral
symptoms .
• Initial onset after a period of apparently normal
early development.
• Onset of symptoms typically occurs as early as
5 months or as late as 48 months
• Often misdiagnosed as autism, cerebral palsy
or non-specified developmental delay
Dr. Andreas Rett in Vienna, Austria
Rett Disorder: Primary Symptoms
• Major symptoms include the following;
– a deceleration in normal head growth, resulting in
acquired microcephaly,
– a loss of previously acquired hand movements, and
the appearance of poorly coordinated gait and/or
trunk movements.
• The loss of existing motor skills.
• development of stereotyped hand movements
(hand wringing or washing type movements.
 Other Symptoms of Rett Disorder
• Other symptoms include regression with deficits
in expressive and receptive language.
• This is usually accompanied by severe
psychomotor retardation.
• Behavior is often autistic-like;
– stereotypic behaviors (e.g., hand movements noted
above),
– a lack of sustained interest in persons and objects and
– a marked decrease in interpersonal contact
 Some General Information
• Prevalence of Rett disorder estimated at 1 in
10,000 to 1 in 22,000 (Percy & Lane, 2009) .
• It occurs primarily in females, among live births.
• It is usually associated with severe mental
retardation.
• It is a disorder marked by rapid deteoriation after
initial onset and a course which is chronic.
• However, sometimes a renewed interest in social
interactions may appear as the person becomes
older.
 Suggestions as to Etiology
• Disorder seems to be caused by mutations of a defective
regulatory MECP2 (meck-pea-two) gene on the X
chromosome (Zoghbi, 2005).
• This gene controls other genes that are involved in the
protein synthesis of a protein called methyl cytosine.
• This protein acts as a biochemical switch that instructs
other genes to turn off and stop producing their own
proteins.
• This abnormalities of this proteins function produce the
neurodevelopmental problems seen in this disorder.
 Why Females Only
• Why is Rett Disorder seen almost exclusively in females?
– Since males have an X and a Y chromosome, they lack a "backup"
copy of the X chromosome that can compensate for a defective one
– Mutations typically lethal to the male fetus
• The diagnosis remains a clinical one
– Not made solely on the basis of MECP2 mutations.
– RS can occur with or without mutations in MECP2, and MECP2
mutations can occur without the diagnosis of RS.
– MECP2 gene 70-90% with “classical” RS
– MECP2 gene 0-30% with atypical RS
 Suggestions of Etiology
• Despite being a gene related disorder, not likely to be
inherited.
• Chances of a second child in family developing Rett disorder
is less than one in 100.
• Other suggestions of a biological etiology include;
– the course of the disorder is usually accompanied by the development
of motor neurological signs,
– almost all show abnormal EEG records
– that there is sometimes evidence of cortical atrophy on CT scans,
– that some show evidence of postmortem neurological abnormalities,
and
– that some show abnormalities of the cerebrospinal fluid’
 Possible Treatments
• Treatment: Multidisciplinary
– No cure
– Treatment is symptomatic — focusing on the management of
symptoms
– Medication may be needed for breathing irregularities and motor
difficulties, and antiepileptic drugs may be used to control seizures
– Monitoring for scoliosis and possible heart abnormalities
– Occupational therapy
– Hydrotherapy may prolong mobility
– Nutritionists to help them maintain adequate nutrition
– Behavioral approaches designed to deal with the behavioral deficits
and excesses associated with the disorder may be useful.
– Would need to be combined with special education approaches to
deal with cognitive impairments, and physical therapy to assist with
the motor problems that result from this condition.
– Family support is essential.
 Long Term Outlook
• Long-Term Prognosis
– Little is known since most known cases are relatively
young.
– Females have a 95% chance of surviving to 25 years old
– Can live into middle age and beyond; Survival rate to age
35 is about 70% (Percy & Price 2009)
– Long term care will likely be necessary
– Morbidity often related to seizure disorder or swallowing
difficulties
– Future: Stem Cell and Gene Therapies
Childhood Disintegrative Disorder
• The disorder was originally labeled "dementia infantilis"
by Heller (1930),
• A severe and disorder occurring after a period of normality.
• Usually develops after age two.
• Involves rapid regression in behavior with a loss of social,
language, and motor skills as well a skills in other areas
(e.g., play, bladder and bowel control).
• Symptoms include impairment in social interaction &
communication, repetitive and stereotyped behaviors as
seen in other PDD’s.
 Other Clinical Manifestations
• The regression or disintegration seen in the
disorder usually takes place over a period of six
to nine months.
• This results in a clinical picture "... of an
overactive child with poor attention-span,
isolation, obsessional behavior, limited but
variable comprehension, minimal and often
inappropriate expressive language, but with
good motor abilities.”
 Disintegrative Disorder vs Autism
• The obsessional and stereotypic behaviors and the
impairment in social interactions that often accompany
this disorder can resemble autistic disorder.
• However, this disorder can be distinguished from
autism by
– its later age of onset (usually 2 to 4 years) and
– the absence of other autistic features.
• Examples of the latter might include specific language
characteristics as well as the obsessive desire for the
maintenance of sameness which is often considered
one of the hallmarks of autism .
Epidemiology and Natural Course
• A pooled estimate of prevalence from four surveys is 1.7 per
100,000.
• This suggests that CDD is very rare and its prevalence is 60 times
less than that for autistic disorder.
• If a rate of 30 per 10,000 is taken for all PDDs, only one child out of
175 children with a PDD diagnosis would meet criteria for CDD
(Fombonne, 2002).
• It is more common in males.
• It course is variable.
– Sometimes, after the initial loss of skills, the condition will
remain static, with limited improvement in social behavior.
– In other cases there is progressive deteoriation
– Most often the problems in social interaction, communication,
and behavior remain relatively constant over time.
 The Issue of Etiology
• Little information is available regarding the etiology of
this disorder.
• Although it is sometimes associated with medical
conditions such as epileptic encephalopathy and
progressive neurological syndromes suggesting CNS
involvement (Wiznitzer, 2009).
• Case studies of children with this disorder have
reported;
– abnormal EEG findings,
– increases in soft neurological signs, and
– postmortem indicators of neurolipidoses.
• While these findings are suggestive, more definitive
investigations into the etiology of this disorder are
needed.
 Treatment
• Despite little information regarding optimal
treatments for this condition, an approach
similar to that suggested for the treatment of
Rett's disorder might be of value in this case as
well.
• Again, the focus would be on behavioral
approaches to modify problematic behavioral
excesses and deficits, along with appropriate
special educational approaches.
 Long Term Outlook
• Loss of skills often reaches a plateau and then there
may be some limited improvement.
• In other cases there is progressive loss of skills.
Those with moderate-to-severe mental retardation or
with an inability to communicate tend to do worse
than those left with a higher IQ and some verbal
communication.
• The disorder is lifelong with long-term impairment of
behavioral and cognitive functioning.
• Risk of seizures increases throughout childhood,
peaking at adolescence and seizure threshold may be
lowered by SSRIs and neuroleptics.6
The End