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LBM 2

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STEP 1
1. Mood : keadaan emosional dalam diri seseorang yang dialami secara subyektif.
2. Afektif : respon emosiaonal yang bisa dinilai melalui ekspresi wajah, pembicaraan,
sikap dan gerak tubuh.
Mood dan afektif, tidak reliabel bisa di gali lagi dg anamnesis
3. Sindroma depresi : sindrom yang menunjukan penurunan afektif dan aktivitas sehari
hari.
Kumpulan gejala diantaranya : kehilangan minat dan kegembiraan, energi yang
mudah turun lelah, kurang konsentrasi, penurunan rasa percaya diri dan
gangguan tidur yang menyebabkan fungsi sosialnya terganggu
STEP 2
1. Mengapa pasien merasa sedih, kehilangan minat dan kegembiraan, kurang semangat
dan tidur terganggu?
2. Mengapa penderita mengalami perubahan afektif yang sebelumnya semangat
menjadi sindroma depresi?
3. Bagaimana hubungan PHK dengan sindroma depresi?
4. Apakah ada hubungan dari umur dan jenis kelamin dengan sindroma depresi?
5. Apa saja faktor yang menyebabkan sindroma depresi?
6. Apa saja derajat depresi?
7. Apa macam-macam mood dan afektif?
8. Apa macam macam dari gangguan mood/afektif?
9. Apa penyebab dari gangguan afektif?
10. Bagaimana cara menilai scoring GAF?
11. Apa terapi yang diberikan pada pasien ini?
STEP 7
1. Mengapa pasien merasa sedih, kehilangan minat dan kegembiraan, kurang semangat
dan tidur terganggu?

Major depressive disorder (MDD) is a common and costly disorder which is
usually associated with severe and persistent symptoms leading to important social
role impairment and increased mortality 1,2. It is one of the most important causes
of disability worldwide 3. The high rate of inadequate treatment of the disorder
remains a serious concern 1.This review is aimed at summarizing the solid evidence
on the etiology and pathophysiology of MDD that is likely relevant for clinical
psychiatry. Neurobiological findings are regarded as solid when they are consistent
and convergent, i.e., they have been confirmed by several studies using the same
method and fit into results from studies using different methodological approaches.
GENES AND PSYCHOSOCIAL STRESS
Family, twin, and adoption studies provide very solid and consistent evidence
that MDD is a familial disorder and that this familiality is mostly or entirely due to
genetic factors 4. This important finding suggests that parental social behavior and
other familial environmental risk factors are not as important in the pathogenesis
of MDD as previously assumed and should not be the major focus of the treatment
of the disorder.
The above-mentioned studies consistently show that the influence of
genetic factors is around 30-40%4. Non-genetic factors, explaining the remaining 60-
70% of the variance in susceptibility to MDD, are individual-specific environmental
effects (including measurement error effects and gene-environment interactions).
These effects are mostly adverse events in childhood and ongoing or recent stress
due to interpersonal adversities, including childhood sexual abuse, other lifetime
trauma, low social support, marital problems, and divorce 5,6.
These results suggest that there is a huge potential in the prevention of
MDD by means of psychosocial interventions (e.g., in schools, at workplace). In
addition, these results mirror the clinical practice of empirically validated
psychotherapies to treat depression 7,8,9, including interpersonal, psychodynamic
and cognitive behavioral psychotherapies and cognitive behavioural analysis system
of psychotherapy, which all focus directly or indirectly on interpersonal difficulties
and skills. This does not exclude the fact that unidentified non-genetic, non-
psychosocial risk factors may also play important roles in some patients (e.g.,
climatic change, medical conditions).
Stress sensitivity in depression is partly gender-specific. While men and
women are, in general, equally sensitive to the depressogenic effects of stressful life
events, their responses vary depending upon the type of stressor. Specifically, men
are more likely to have depressive episodes following divorce, separation, and
work difficulties, whereas women are more sensitive to events in their proximal
social network, such as difficulty getting along with an individual, serious illness, or
death 10. These findings point to the importance of gender-sensitive psychosocial
approaches in the prevention and treatment of MDD.
In contrast to the very solid evidence from epidemiological studies on broad
risk factor domains, there is no solid evidence for specific genes and specific gene-
by-environment interactions in the pathogenesis of MDD. Genome-wide association
studies have indicated that many genes with small effects are involved in complex
diseases, increasing the difficulty in identifying such genes 11. While there has been
progress in the search for risk genes for several complex diseases despite this
methodological problem 12, psychiatric conditions have turned out to be very
resistant to robust gene identification. For example, based on a community-based
prospective study, it has been proposed that a specific genetic variation in the
promoter region of the serotonin transporter (a target of antidepressant drugs)
interacts with stressful life events in the pathogenesis of depression 13. Although
there is high clinical and neurobiological plausibility of this interaction, a recent
meta-analysis yielded no evidence that the serotonin transporter gene alone or in
interaction with psychological stress was associated with the risk of depression 14.
The limited success of genetic studies of depression has been related to use
of current classification schemas including ICD-10 and DSM-IV. These diagnostic
manuals are based on clusters of symptoms and characteristics of clinical course
that do not necessarily describe homogenous disorders but instead reflect
common final pathways of different pathophysiolgical processes 15,16. The
clinician should be aware that family history will continue to be the most solid source
of information to estimate the genetic risk of MDD.

STRESS HORMONES AND CYTOKINES
Corticotropin-releasing hormone (CRH) is released from the hypothalamus in
response to the perception of psychological stress by cortical brain regions. This
hormone induces the secretion of pituitary corticotropin, which stimulates the
adrenal gland to release cortisol into the plasma. The physiologic response to stress
is partly gender-specific: women show generally greater stress responsiveness than
men, which is consistent with the greater incidence of major depression in
women17. Moreover, men show greater cortisol responses to achievement
challenges, whereas women show greater cortisol responses to social rejection
challenges 18.

Although MDD is considered as a stress disorder, most subjects treated for MDD
have no evidence of dysfunctions of the hypothalamic-pituitary-adrenal axis
(HPA) 19. However, some subjects with MDD do show abnormalities of that axis
and of the extrahypothalamic CRH system 20. Altered stress hormone secretion
appeared to be most prominent in depressed subjects with a history of childhood
trauma 21. Elevated cortisol may act as a mediator between major depression and
its physical long-term consequences such as coronary heart disease, type II diabetes,
and osteoporosis 22.
The importance of HPA axis dysfunction for the efficacy of antidepressants is
a matter of debate 23. This axis is regulated through a dual system of
mineralocorticoid (MR) and glucocorticoid (GR) receptors. Decreased limbic GR
receptor function 24,25 and increased functional activity of the MR
system 26suggest an imbalance in the MR/GR ratio in stress-related conditions such
as MDD. Epigenetic regulation of the glucocorticoid receptors has been associated
with childhood abuse 27. Such environmental programming of gene expression may
represent one possible mechanism that links early life stress to abnormal HPA axis
function and increased risk of MDD in adults.
While the CRH stimulation test (dex/CRH test) 28 is a sensitive measure of
the HPA axis dysfunction in depression, the specificity of this test for MDD is low.
However, non-suppression in the dex/CRH test has consistently predicted increased
risk for depressive relapse during clinical remission 23. Additionally, the
measurement of waking salivary cortisol concentration has been shown to be a
simple and sensitive test for HPA axis hyperactivity in depression 29.
Hypercortisolemia is almost exclusively found in subjects with severe and
psychotic depression, in whom glucocorticoid antagonists may have some
therapeutic effect 30.
There is convergent evidence for CRH to play a major role in the pathogenesis
of certain types of depression. Levels of CRH in the cerebrospinal fluid are elevated
in some depressed subjects 31. Post-mortem studies reported an increased
number of CRH secreting neurons in limbic brain regions in depression 32, likely
reflecting a compensatory response to increased CRH concentrations 33. In addition,
CRH produces a number of physiological and behavioral alterations that resemble
the symptoms of major depression, including decreased appetite, disrupted sleep,
decreased libido, and psychomotor alterations 34. There is also preliminary evidence
that CRH1 receptor antagonists reduce symptoms of depression and anxiety 35.
Sickness behavior as a result of an activation of the inflammatory response
system shares many symptoms with depression, including fatigue, anhedonia,
psychomotor retardation, and cognitive impairment. Additionally, the measurement
of waking salivary cortisol concentration has been shown to be a simple and
sensitive test for HPA axis hyperactivity in depression 36. The prevalence of
depression as an unwanted effect of recombinant interferons is around 30% 37. In
animals, blocking pro-inflammatory cytokine-mediated signaling produces
antidepressant-like effects38. Clinical data suggest that cytokines may play a role in
the pathophysiology of a subgroup of depressed subjects, particularly those with
comorbid physical conditions 36. The antidepressant enhancing effect of
acetylsalicylic acid 39 points to the possible clinical relevance of
psychoneuroimmunology in clinical depression research.
Taken together, the laboratory tests with the highest potential to be clinically
useful in the care of depressed individuals are based on abnormalities of the
neuroendocrine and neuroimmune systems. Despite the large amount of basic
science data suggesting that the HPA axis is importantly involved in the
pathophysiology of depression, the effect of pharmacological modulation of this
neuroendocrine system as antidepressant therapy has been disappointing. The link
between childhood trauma and a permanently altered physiologic stress system
points to the use of specific psychotherapies in the treatment of depressed
patients with a history of early life trauma 40.

NEUROTRANSMITTERS AND MOOD
Neurotransmitters, especially noradrenaline and serotonin (also called 5-HT)
are believed to be key in the control of mood and emotional behavior. The
neurotransmitters we are concerned with - monoamines - all share a similar
chemical structure and are also known as biogenic amines. These neurotransmitters
include adrenaline, dopamine, serotonin and noradrenaline.

Noradrenaline and the Noradrenergic System
The noradrenaline system is referred to as the noradrenergic system, and
receptors specific to noradrenaline or adrenaline are both referred to as adrenergic
receptors.
Noradrenaline, which is synthesized from the dietary amino acid tyrosine, is
believed to play a major role in the control of mood and emotional behavior.
The major concentration of noradrenergic neurons is in the locus ceruleus in the
midbrain. The axons of these neurons project upward through the forebrain to the
cerebral cortex, the limbic system, the thalamus, and the hippocampus.

the various parts of the brain along the noradrenergic pathway
Noradrenaline, a key neurotransmitter involved in the control of mood and
emotional behavior, is believed to inhibit or stimulate a variety of emotional
responses such as anxiety, aggression, stress, and sleep patterns.
Noradrenaline is released by a presynapse, and binds to receptor sites on a
postsynaptic neuron. Residual noradrenaline (NE) is taken back up into the
presynaptic neuron (reuptake) where it is recycled into storage vesicles or
metabolized by the enzyme MAO (degradation).

Serotonin and the Serotonergic System
Like noradrenaline, serotonin (5-HT) is a key neurotransmitter involved in the
control of mood. The axons of serotonergic neurons originate in the raphe nuclei of
the brain stem and project to the cerebral cortex, the limbic system, cerebellum,
and spinal cord.

the various parts of the brain along the serotonergic pathway
Serotonin is involved in the regulation of pain, pleasure, anxiety, panic,
arousal, and sleep behavior (the sleep-wake cycle). Serotonin (5-HT) is synthesized
from a dietary acid called tryptophan. Like noradrenaline, serotonin is a
neurotransmitter. As such, serotonin is released by a presynaptic neuron, travels
across a synapse, and binds to a receptor site in a postsynaptic neuron.

Residual serotonin may also be recycled by the presynaptic neuron through
reuptake.

Neurotransmitter Receptor Sites
Just as there are different types of neurotransmitters, there are different
receptor sites, each with an affinity for a specific neurotransmitter.

In addition to the receptor sites located on postsynaptic neurons in the brain,
receptor sites exist on neurons in other parts of the body, such as the gut or salivary
glands. (The side effect profile of antidepressant drugs varies with their affinity for
these receptors.)
In recent years, many subtypes of these receptors have been discovered.
Some adrenergic receptors, for example, are now known to be associated with
inhibitory processes while others are stimulatory. While the science of mood
disorders is still very incompletely understood, some very useful theories have
emerged over the past two decades.
The Biogenic Amine Hypothesis.
In the early 1950s, researchers noticed that drugs that decreased monoamines
precipitated depression, and drugs that increased monoamines relieved depression.
The Biogenic Amine Hypothesis states that depression is caused by a deficiency of
monoamines, particularly noradrenaline and serotonin.



Monoamine Deficiency
According to this hypothesis, depression can be alleviated by drugs that
increase the availability of noradrenaline and serotonin.
One method of increasing monoamines centers around the action of MAO.
Remember that MAO degrades neurotransmitters.



Action of MAOI's
Blocking the action of MAO leads to an increased availability of neurotransmitters.
When the action of MAO is blocked, neurotransmitters are not metabolised, so
they accumulate in the presynaptic neuron. Drugs which block the metabolism of
noradrenaline and serotonin via inhibition of MAO are called MAO inhibitors, or
MAOIs. MAOIs were among the first clinically proven antidepressants. Taken
chronically, MAOIs also produce desensitization and down-regulation of postsynaptic
receptors.
Another way to increase monoamines involves blocking the process of
reuptake. Blocking reuptake prevents the presynaptic neuron from reclaiming
neurotransmitter, which increases the amount of neurotransmitter in the synaptic
cleft.



Action of TCA's
Drugs were developed in the 1950s that blocked reuptake in just this way. These
drugs - still widely used today - are called tricyclic antidepressants or TCAs.
The Biogenic Amine Hypothesis has been the cornerstone of research on
depression for more than 30 years. However, an important fact cannot be explained
by the Biogenic Amine Hypothesis. Laboratory tests indicate that antidepressants
such as TCAs and MAOIs increase available neurotransmitters quite rapidly - within
a matter of hours. Yet, typically, clinical relief takes much longer. A person
suffering from depression may not experience significant relief for as long as 6 to 8
weeks.
The Receptor Sensitivity Hypothesis
The Biogenic Amine Hypothesis alone cannot explain the delay in time of onset of
clinical relief of depression of up to 6-8 weeks.
Recall how the body compensates for a deficit or excess of neurotransmitter.



Supersensitivity (up-regulation)
Supersensitivity is a compensatory response of the postsynaptic neuron
when it receives too little stimulation. The neuron tries to make up for a lack of
stimulation by increasing receptor responsiveness. Over time, the postsynaptic
neuron may also compensate for lack of stimulation by synthesizing additional
receptor sites. This process is known as up-regulation.
By increasing the amount of neurotransmitter in the cleft, you can normalize
responsiveness. Increased neurotransmitter increases stimulation of receptor sites,
which prompts the postsynaptic neuron to compensate by decreasing receptor
sensitivity, a process known as desensitization.
The postsynaptic neuron is also thought to compensate for increasing
stimulation by decreasing the number of receptor sites, a process known as down-
regulation.
As we know, antidepressant drugs are thought to work by increasing the
amount of neurotransmitter in the cleft. They do this by blocking metabolism of
monoamines - the MAOIs - or by blocking reuptake - the TCAs. Most TCAs are more
effective in blocking noradrenaline reuptake than serotonin reuptake.



Actions of Early Antidepressant Drugs
Chronic administration of TCAs or MAOIs is thought to alter the
responsiveness and/or the number of postsynaptic receptor sites. Observation of
this long-term effect of antidepressants led to the Receptor Sensitivity Hypothesis.
This hypothesis proposes that depression is the result of a pathological alteration
(supersensitivity and up-regulation) in receptor sites, which results from too little
stimulation by monoamines, i.e., a deficiency of noradrenaline and serotonin in
the cleft.
Chronic administration of TCAs or MAOIs results in increased availability of
noradrenaline and serotonin. This causes desensitization (the uncoupling of receptor
sites) and possibly down-regulation (a decrease in the number of receptor sites).
According to this hypothesis, relief from depression symptoms comes from a
normalization of receptor sensitivity.
According to the Receptor Sensitivity Hypothesis, antidepressant drugs
achieve their clinical effect by reducing receptor supersensitivity. This theory is an
important step toward understanding the long delay between administration of
TCAs and MAOIs and clinical response.
While TCAs are effective in blocking the reuptake of noradrenaline and
serotonin into the presynaptic neuron, they are non-selective: they also block
postsynaptic receptor sites, including cholinergic (muscarinic), histaminergic, and
adrenergic receptor sites. Blockade of histaminergic receptors can lead to sedation,
weight gain, and hypotension. In the elderly, this is a particular problem, since it can
result in fainting or falls. TCAs also block muscarinic receptors, which can lead to
blurred vision, dry mouth, constipation, urinary retention, confusion, and delirium.



Non-specific Blockade of TCA's
The Serotonin-only Hypothesis.
Early in the 1980s, drugs were introduced that selectively blocked serotonin
reuptake, resulting in more serotonin available in the cleft. These drugs were known
as selective serotonin reuptake inhibitors, or SSRIs.
Unlike the TCAs, which are non-selective, the SSRIs may have fewer serious
side effects and are therefore easier for patients to tolerate. This has led to
the Serotonin-only Hypothesis which emphasizes the role of serotonin in depression
and downplays noradrenaline.



Specific Serotonin Blockade of SSRI's
But the serotonin-only theory has shortcomings: it does not explain why there is a
delay in onset of clinical relief; it does not explain the role of noradrenaline in
depression.
A study at Yale tested the serotonin-only hypothesis and
demonstrated the importance of noradrenaline. The test group consisted of
depressed patients who were being treated successfully with either selective
serotonin reuptake inhibitors (SSRIs) or a non-selective TCA. All these patients were
placed on a tryptophan-free diet. (Remember, tryptophan is the precursor of
serotonin.) Researchers reasoned that is serotonin alone were responsible for
depression, all patients should relapse when the tryptophan-free diet caused their
serotonin levels to fall. In fact, only those patients taking SSRIs relapsed, while
those on TCAs did not. This suggested that both noradrenaline and serotonin play a
critical role in depression.
Another key observation came from laboratory studies. When noradrenergic
neurons are destroyed in laboratory animals, drugs that affect serotonin do not
have their usual effects. Likewise, when serotonergic neurons are destroyed, drugs
that affect noradrenaline do not have their usual effects.
The Permissive Hypothesis
Current research suggests that mood is controlled by a balance of
noradrenaline and serotonin, not by absolute levels of these neurotransmitters or
their receptors. According to this hypothesis - the Permissive Hypothesis - the
control of emotional behavior results from a balance between noradrenaline and
serotonin.
According to this theory, both the manic phase and the depressive phase of
bipolar disorder are characterized by low central serotonin function. Evidence
suggests that brain serotonin systems dampen or inhibit a range of functions
involving other neurotransmitters. Mood disorders result from the removal of the
serotonin damper.
The Permissive Hypothesis postulates that low levels of serotonin permit
abnormal levels of noradrenaline to cause depression or mania. If serotonin cannot
control noradrenaline, and noradrenaline falls to abnormally low levels, the patient
becomes depressed. On the other hand, if the level of serotonin falls and the level of
noradrenaline becomes abnormally high, the patient becomes manic.

THE NEUROIMAGING OF DEPRESSION
Although many historical attempts to localize mental functions have failed,
they have considerably contributed to a modern neuroscientific understanding of
mental disorders 60. The development of neuroimaging techniques has opened up
the potential to investigate structural and functional abnormalities in living
depressed patients. Unfortunately, the diversity of imaging techniques used, the
relatively small and heterogeneous study samples studied, and the limited overlap of
results across imaging paradigms 61 make it difficult to reliably identify neuronal
regions or networks with consistently abnormal structure or function in MDD.
Functional imaging studies have provided the most limited overlap of
findings. This may be due to methodological limitations and/or the complexity of
neurocircuitry involved in MDD. A recent meta-analytic study found the best
evidence for abnormal brain activity in MDD in lateral frontal and temporal
cortices, insula, and cerebellum. In these brain regions activity was decreased at
rest, they showed a relative lack of activation during induction of negative emotions,
and an increase in activity following treatment with serotonin reuptake inhibitors.
Opposite changes may exist in ventromedial frontal areas, striatum and possibly
other subcortical brain regions 61.

More solid evidence has been provided by structural imaging and post-
mortem studies. A recent meta-analytic study on brain volume abnormalities in
MDD revealed relatively large volume reductions in the ventromedial prefrontal
cortex, particularly in the left anterior cingulate and in the orbitofrontal cortex.
Moderate volume reductions were found in the lateral prefrontal cortex,
hippocampus and striatum 62. Post-mortem studies consistently identified a
reduction in glia cell density in dorsal, orbital and subgenual prefrontal cortices, as
well as in the amygdala 63,64.
Overall, functional, structural and post-mortem studies suggest that
structural and functional abnormalities in the left subgenual cingulate cortex are
the most solid neuroanatomical finding in MDD. Volume reduction in this region
was found early in illness and in young adults at high familial risk for MDD 65,
suggesting a primary neurobiological abnormality associated with the etiology of the
illness. Humans with lesions that include the subgenual prefrontal cortex showed
abnormal autonomic responses to social stimuli 66, and rats with left-sided lesions in
this region had increased sympathetic arousal and corticosterone responses to
restraint stress 67. Most importantly, chronic deep brain stimulation to reduce the
potentially elevated activity in the subgenual cingulated cortex produced clinical
benefits in patients with treatment-resistant depression 68.
In summary, despite the considerable heterogeneity of findings from
neuroimaging studies, there is convergent evidence for the presence of
abnormalities in the subgenual prefrontal cortex in some patients with MDD.
Neuroanatomical research in depression is of great clinical interest, since novel
antidepressant treatments such as deep brain stimulation can target specific brain
regions. In addition, there are promising leads for neuroimaging findings to predict
the likelihood of responses to specific treatments 69.

THE NEUROTROPHIC HYPOTHESIS OF DEPRESSION
Risk factors for depressive episodes change during the course of the illness.
The first depressive episode is usually reactive, i.e., triggered by important
psychosocial stressors, while subsequent episodes become increasingly
endogenous, i.e., triggered by minor stressors or occurring spontaneously 70.
There is consistent evidence that the volume loss of the hippocampus and other
brain regions is related to the duration of depression 71, suggesting that untreated
depression leads to hippocampal volume loss, possibly resulting in increased stress
sensitivity 72 and increased risk of recurrence 73.
Glucocorticoid neurotoxicity, glutamatergic toxicity, decreased
neurotrophic factors, and decreased neurogenesis have been proposed as possible
mechanisms explaining brain volume loss in depression. There is no solid evidence
on any of these mechanisms, since there are no imaging tools to directly examine
neurotoxic and neurotrophic processes in vivo. Brain derived neurotrophic factor
(BDNF) has attracted considerable interest. Specifically, preclinical studies have
shown correlations between stress-induced depressive-like behaviors and decreases
in hippocampal BDNF levels, as well as enhanced expression of BDNF following
antidepressant treatment 74. The clinician should be aware of the potentially brain-
damaging effect of depression and treat depressed patients as early and effectively
as possible.

ALTERED GLUTAMATERGIC AND GABAERGIC NEUROTRANSMISSION
A series of magnetic resonance spectroscopy studies consistently showed
reductions in total gamma-aminobutyric acid (GABA) concentrations in the
prefrontal and occipital cortex in acute depression 75. This may reflect acute stress
effects, since psychological stress seems to induce presynaptic down-regulation of
prefrontal GABAergic neurotransmission 76. Alternatively, low total GABA
concentration may reflect reduction in the density and size of GABAergic
interneurons 77. In addition, chronic stress may reduce GABA-A receptor function,
possibly through changes in neuroactive steroid synthesis 78. Contradictory
evidence of the GABA hypothesis of depression includes the lack of effects of
GABAergic drugs on core depressive symptoms 79 and normal prefrontal GABA
concentration in subjects with remitted MDD 80.
Several lines of evidence suggest a dysfunction of the glutamate
neurotransmitter system in MDD: a single dose of the glutamate N-methyl-D-
aspartate (NMDA) receptor antagonist ketamine produced rapid and large
antidepressant effects in patients with treatment-resistant MDD 81; inhibitors of
glutamate release (e.g., lamotrigine, riluzole) demonstrated antidepressant
properties 82; abnormal glutamate levels were found in depressed subjects as
determined by magnetic resonance spectroscopy75; and there is evidence for
abnormal NMDA signaling in post-mortem tissue preparations 83. Since glutamate is
the major excitatory neurotransmitter involved in almost every brain activity, the
characterization of the specific role of glutamate in depression deserves further
investigation (e.g., there are promising leads that the metabotropic glutamate
receptor 5 is specifically involved in MDD 84).

CIRCADIAN RHYTHMS
Sleep disturbances and daytime fatigue are diagnostic criteria for MDD,
suggesting impaired sleep-wake regulation in depressed patients. In addition, some
depressive symptoms may show diurnal variations (mood, psychomotor activity,
accessibility of memories of positive and negative experiences), and a subgroup of
patients with MDD may have a circadian rhythm disorder 85. In healthy young
subjects, moderate changes in the timing of the sleep-wake cycle had specific
effects on subsequent mood 86. In depressed patients, manipulations of circadian
rhythms (light therapy, sleep deprivation, phase advance treatment) can have
antidepressant efficacy.
Based on these findings, circadian abnormalities have been hypothesized to
be etiologically associated with MDD 16. The association between phase advance of
the sleep-wake cycle and phase advances in nocturnal cortisol secretion; shortened
REM latency in some subjects with MDD; and the effect of antidepressants on
circadian rhythms of behavior, physiology, and endocrinology contribute to the
biological foundation of this hypothesis 85,87,88. Despite of the many promising
findings, the molecular and genetic underpinnings of this hypothesis are largely
unknown. It remains to be determined whether antidepressant effects of new
therapeutics such as agomelatine directly relate to normalization of circadian
rhythms 87.Based on these findings, circadian abnormalities have been hypothesized
to be etiologically associated with MDD 16..

CONCLUSIONS
The many theories of depression and the relatively low response rate of all
available antidepressant treatments clearly argue against a unified hypothesis of
depression and suggest that depression is a clinically and etiologically
heterogeneous disorder.
This encourages research on predictors of the response to therapeutic
interventions using biomarkers such as neuroimaging and neuroendocrine tests in
combination with genotyping for inter-individual variability with respect to stress
sensitivity and antidepressant drug action.
The identification of reliable predictors of therapeutic outcomes will allow for
the development of personalized medicine that has the potential to individually
tailor interventions and to open up new pathways in the evaluation of novel
therapeutic approaches.
Melatonin - Pada siang hari, tubuh Anda berubah dari serotonin menjadi
melatonin.
Tubuh Anda kemudian menyimpan melatonin pada kelenjar pineal di dalam otak
Anda. Ketika tingkat penurunan cahaya pada malam hari, kelenjar pineal
mengeluarkan melatonin, membantu Anda untuk tertidur. Di pagi hari, siang hari
sinyal kelenjar pineal Anda untuk menutup produksi melatonin, membantu Anda
untuk bangun. Jika kadar serotonin Anda rendah, kemungkinan besar, Anda tidak
memproduksi melatonin yang cukup. Dan tanpa melatonin yang cukup, tubuh
Anda tidak dapat secara memadai mengatur tidur Anda / siklus bangun. Studi
menunjukkan bahwa mengambil dalam jumlah yang tepat dari melatonin dapat
mengembalikan tidur pada orang dewasa lebih dari 50. Ambil 1-3 mg setengah jam
sebelum Anda pergi tidur.
(Dr. Frank Shallenberger, www.realcuresletter.com)

Fase Tidur
Terdapat dua fase utama tidur, yaitu Non-Rapid Eye Moevement (NREM) dan Rapid
Eye Movement (REM). Keterangan serta tahapan-tahapan yang terjadi di dalamnya
adalah sebagai berikut.
Fase Tidur: Non-REM (NREM)
Non-rapid eye movement terbagi menjadi 4 tahap: N1 N4, yang masing-masingnya
lebih dalam dari yang lainnya.
N1 dimulai saat kita mulai tertidur dan berlangsung dalam waktu yang
sangat singkat, sekitar 5 menit. Mata bergerak sangat lambat di bawah
kelopak, aktifitas otot menurun, dan pada tahap ini kita sangat mudah
terbangun. Banyak orang yang merasakan sensasi seperti terjatuh pada
tahap ini, yang menyebabkan kontraksi otot secara tiba-tiba (disebut hypnic
myoclonia).
N2 tahap ini bisa dikatakan sebagai tahap awal saat kita benar-benar tidur,
dan berlangsung antara 10-30 menit. Pada tahap ini otot tubuh menjadi
sangat rileks, aktifitas otak lebih lambat, gerakan mata berhenti, detak
jantung melambat dan temperatur tubuh menurun. Seseorang agak susah
terbangun di tahap ini.
N3 & N4 kedua tahap ini merupakan tahap paling dalam dari tidur NREM.
Sangat sulit untuk terbangun pada tahap ini, dan jika terbangun kita akan
mengalami disorientasi serta membutuhkan penyesuaian selama beberapa
menit. Pada bagian terdalam dari tahap ini, aktifitas otak sangat lambat,
dan aliran darah lebih banyak diarahkan ke otot, mengisi energi fisik tubuh.
Selama tahap tidur lelap (deep sleep) pada fase NREM, tubuh akan meregenerasi
dan memperbaiki sel-sel tubuh, serta memperkuat sistem imun tubuh.
Fase Tidur: REM
Fase REM biasanya terjadi 70 90 menit setelah kita tertidur. Fase tidur ini lebih
dalam dari NREM. Selama fase REM ini, biasanya mata bergerak-gerak/berkedut
(itulah mengapa fase ini disebut rapid eye movement) dan napas menjadi lebih tidak
teratur, aktifitas otak dan ritme detak jantung juga meningkat.
Umumnya mimpi terjadi saat fase tidur REM. Namun otak melumpuhkan otot-otot
tubuh, khususnya tangan dan kaki, sehingga kita tidak ikut bergerak saat bermimpi.
Siklus NREM dan REM dalam Tidur

Selama tidur, seseorang biasanya melewati setidaknya 3 tahapan dalam NREM
sebelum masuk ke fase REM. Siklus atau perputaran antara dua fase ini akan terus
berulang selama tidur, yang masing-masingya membutuhkan waktu antara 1 2 jam.
Dan siklus ini dapat berulang sekitar 3 hingga 4 kali dalam satu malam.

GREGOR HASLER
.
.

PATHOPHYSIOLOGY OF DEPRESSION. World Psychiatry. Oct 2010; 9(3):
155161.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2950973/

2. Mengapa penderita mengalami perubahan afektif yang sebelumnya bersemangat
menjadi sindroma depresi?
MANIA
Trias Manic:
1. Flight of ideas
2. Euforia dan reaksi emosional yang labil, eksaltasi (perasaan senang dan
semangat yang ekstrim)
3. Sikap yang berubah-ubah dan tingkah laku yang hiperaktif
Nafsu bergerak yang banyak dan dapat terjadi logorhoe (bicara cepat dan
banyak)
Gejala tambahan:
1. Selalu bangga diri, sikap sombong, puas terhadap dirinya.
2. Kadang-kadang ada waham kebesaran.
Tanda
Penampilan Umum dan perilaku: agitasi psikomotor, menarik perhatian,
pakaian berwarna semarak,dadndanan berlebihan, kombinasi pakaian aneh,
intrusive, menghibur,mengancam,hipereksitasi.
Afek:labil, kuat
Mood: euforik, ekspansif, iritabel, menuntut,bercanda
Bicara;menekan, keras,dramatic, berlebihan dapat menjadi inkoheren
Isi pikiran: harga diri sangat tinggi,grandiositas, egosentrik tinggi,waham dan
lebih jarang halusinasi
Proses fikiran; flight of ideas(jika berat dpt menjadi inkoheren), pikiran
berpacu, neologisme,asosiasi bunyi(clang), sirkumstansial,
tangensial(mendadak berubah topic).
Sensorium: sangat mudah dialihkan, sulit konsentrasi.
Tilikan: sering terganggu.
Gejala
Perilaku keliru dan disinhibisi(semena-mena)
- Membuang uang berlebihan
- Berjudi berlebihan
- Hiperseksualitas, promiskusitas
Terlampau kepanjangan dalam aktivitas dan tanggung jawab
Toleransi frustasi rendah
Tanda vegetative
- Naiknya libido
- penurunanBB dan anoreksia
- Insomnia( diungkapkan sebagai tak perlu tidur)
- Energi berlebihan

DEPRESI
Gejala Utama:
Afek depresi
Kehilangan minat dan kegembiraan
Berkurangnya energi yang menuju meningkatnya keadaan yg mudah lelah
(rasa lelah yg nyata sesudah kerja sedikit saja) dan menurunnya aktivitas
Gejala Tambahan:
Konsentrasi dan perhatian berkurang
Harga diri dan kepercayaan diri berkurang
Gagasan tentang rasa bersalah dan tidak berguna
Pandangan masa depan yang suram dan pesimistis
Gagasan atau perbuatan membahayankan diri atau bunuh diri
Tidur terganggu
Nafsu makan menurun
(Dr. Rusdi Maslim, PPDGJ III)
The Permissive Hypothesis
Current research suggests that mood is controlled by a balance of
noradrenaline and serotonin, not by absolute levels of these neurotransmitters or
their receptors. According to this hypothesis - the Permissive Hypothesis - the
control of emotional behavior results from a balance between noradrenaline and
serotonin.
According to this theory, both the manic phase and the depressive phase of
bipolar disorder are characterized by low central serotonin function. Evidence
suggests that brain serotonin systems dampen or inhibit a range of functions
involving other neurotransmitters. Mood disorders result from the removal of the
serotonin damper.
The Permissive Hypothesis postulates that low levels of serotonin permit
abnormal levels of noradrenaline to cause depression or mania. If serotonin cannot
control noradrenaline, and noradrenaline falls to abnormally low levels, the patient
becomes depressed. On the other hand, if the level of serotonin falls and the level of
noradrenaline becomes abnormally high, the patient becomes manic.




Abnormally High Noradrenaline : Manic Patient
According to this hypothesis, antidepressant drugs are effective to the degree that
they reinstate the ability of serotonin to control noradrenaline, thus restoring the critical
balance that controls emotional behavior.
A new class of antidepressant drugs, serotonin-noradrenaline reuptake inhibitors
(SNRIs) work to selectively block reuptake of both noradrenaline and serotonin, thereby
increasing levels of both monoamines. The SNRIs have very little affinity for other
postsynaptic receptor sites and are therefore less likely to produce some of the side effects
associated with TCAs.
The Electrolyte Membrane Hypothesis
This theory is largely based on studies in the 1960s of state related fluctuations in
manic depressive illness such as urine volume and body weight. This hypothesis largely died
out after the 1960s but may be reemerging with the resurgence in the literature in the
biochemistry and biophysics of membrane functions. For example, the lithium-sodium
counterflow mechanism in red cells has been described and protein structural differences
between patients with bipolar-polar disorder and controls have been revealed. The
mechanism of action of lithium in bipolar disorder is still not understood.
The Neuroendocrine Hypothesis.
According to this hypothesis, pathological mood states are explained or contributed to by
altered endocrine function. This theory historically grew out of observations that altered
mood states were associated with thyroid or Cushings disease. Current explorations of
pathophysiology using neuroendocrine theories have tended to result in research tools
such as the dexamethasone suppression test becoming diagnostic tools, perhaps
prematurely.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2950973/
3. Perbedaan belanja normal dg suka belanja?
Berbelanja adalah kegiatan yang menyenangkan dan bisa menghilangkan stres
terutama bagi kaum perempuan. Tapi saat orang berbelanja ternyata ada perang di
otak.

Peneliti menemukan adanya tarikan perang saraf di otak ketika seseorang
berbelanja. Belanja merupakan suatu kegiatan yang melibatkan interaksi berbagai
faktor mulai dari genetik sampai tata letak dari suatu mal. Faktor-faktor ini
mempengaruhi dorongan seseorang untuk membeli sesuatu.

Penelitian yang dipimpin oleh ahli saraf Profesor Brian Knutson dari California
menuturkan adanya tarikan perang saraf di otak ketika seseorang berbelanja. Hasil
penelitiannya dilaporkan dalam jurnal Neuron.

Hal yang terjadi di otak dan memainkan peran sentral ketika berbelanja adalah
meningkatnya produksi neurotransmitter dopamin, yaitu respon menyenangkan
yang berhubungan dengan makanan dan seks.

Tapi saat seseorang memikirkan harga dari barang tersebut otak akan
mengaktifkan insula, yaitu suatu bagian dari korteks otak besar yang memainkan
peran untuk merenungkan kerugian (untung ruginya).

"Ketika seseorang memutuskan untuk membeli sesuatu, maka ia akan membuat
keputusan emosional dan rasional. Seseorang memiliki keinginan untuk percaya
bahwa ia membuat keputusan yang rasional, walaupun kenyataanya tidak. Hal ini
yang menyebabkan terjadinya perang saraf di otak," ujar psikolog Adam Ferrier,
seperti dikutip dari ABC.net.au.

Berdasarkan laporan dalam Journal of Consumer Research apapun barang yang
dipilih oleh seseorang baik saat membeli cokelat atau mobil sekalipun semuanya
dipengaruhi oleh faktor genetik.

Selain itu jenis kelamin juga memberikan perbedaan dalam berbelanja. Perempuan
memiliki afinitas pemikiran yang besar saat berbelanja, karenanya ia akan berjalan
santai di setiap toko, memeriksa barang, membandingkan produk dan nilainya,
berinteraksi dengan staf penjual, mengajukan pertanyaan, mencobanya hingga
akhirnya melakukan pembelian.

Sedangkan pada laki-laki memiliki pemikiran yang berbeda, umumnya ia sudah tahu
apa yang diinginkannya sehingga langsung mencari barang tersebut serta memiliki
sedikit kesabaran untuk browsing.

Oniomaniacs, or buying maniacs, have been of interest to psychiatrists since
Kraepelin first coined the term in 1915. Along with pyromania, kleptomania, and alcoholism,
Bleuler (1924) later included oniomania under The Reactive Impulses (Impulsive Insanity of
Kraepelin). He described it as follows:
The particular element is impulsiveness; they cannot help ity the patients are
absolutely incapable to think differently, and to conceive the senseless consequences of
their act, and the possibilities of not doing it. They do not even feel the impulse, but they
act out of their nature like the caterpillar which devours the leaves
Shirley Lee*, Avis Mysyk. 2004. The medicalization of compulsive buying.Department of
Anthropology, Fletcher Argue Building, University of Manitoba, Winnipeg, Manitoba,
Canada R3T 2N2
4. Hubungan suka belanja dg gangguan afektif dan mood?
ETIOLOGY
The etiology of CBD is unknown, though speculation has settled on developmental,
neurobiological, and cultural influences. Psychoanalysts (7-9) have suggested that early life
events, such as sexual abuse, are causative factors. Yet, no special or unique family
constellation or pattern of early life events has been identified in persons with CBD.
Neurobiological theories have centered on disturbed neurotransmission, particularly
involving the serotonergic, dopaminergic, or opioid systems. Selective serotonin reuptake
inhibitors (SSRIs) have been used to treat CBD (27,34- 38), in part because investigators
have noted similarities between CBD and obsessive-compulsive disorder, a disorder known
to respond to SSRIs. Dopamine has been theorized to play a role in "reward dependence",
which has been claimed to foster "behavioral addictions" (e.g., CBD, pathological gambling)
(39). Case reports suggesting benefit from the opiate antagonist naltrexone have led to
speculation about the role of opiate receptors (40,41). There is currently no direct evidence
to support the role of these neurotransmitter systems in the etiology of CBD.
Cultural mechanisms have been proposed to recognize the fact that CBD occurs mainly in
developed countries (42). Elements which appear necessary for the development of CBD
include the presence of a market-based economy, the availability of a wide variety of
goods, disposable income, and significant leisure time. For these reasons, CBD is unlikely to
occur in poorly developed countries, except among the wealthy elite (Imelda Marcos and
her many shoes come to mind).
PSYCHIATRIC COMORBIDITY
Persons with CBD frequently meet criteria for Axis I disorders, particularly mood disorders
(21-100%) (27,34), anxiety disorders (41-80%) (10,12), substance use disorders (21-46%)
(11,29), and eating disorders (8-35%) (10,27). Disorders of impulse control are also relatively
common in these individuals (21-40%) (10,11).
Schlosser et al (12) found that nearly 60% of subjects with CBD met criteria for at least one
Axis II disorder. While there was no special "shopping" personality, the most frequently
identified personality disorders were the obsessive-compulsive (22%), avoidant (15%), and
borderline (15%) types. Krueger (7), a psychoanalyst, described four patients who he
observed to have aspects of narcissistic character pathology.
DONALD W BLACK
1

A review of compulsive buying disorder. . World Psychiatry. Feb 2007; 6(1): 1418.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1805733/

5. Bagaimana hubungan PHK dengan sindroma depresi? Sudah di no.1
6. Apakah ada hubungan dari umur dan jenis kelamin dengan sindroma depresi? Jenis
kelamin di no.1
7. Apa saja faktor yang menyebabkan sindroma depresi? Sudah No.1
8. Apa saja derajat depresi?
DEPRESI
Gejala Utama:
Afek depresi
Kehilangan minat dan kegembiraan
Berkurangnya energi yang menuju meningkatnya keadaan yg mudah lelah
(rasa lelah yg nyata sesudah kerja sedikit saja) dan menurunnya aktivitas
Gejala Tambahan:
Konsentrasi dan perhatian berkurang
Harga diri dan kepercayaan diri berkurang
Gagasan tentang rasa bersalah dan tidak berguna
Pandangan masa depan yang suram dan pesimistis
Gagasan atau perbuatan membahayankan diri atau bunuh diri
Tidur terganggu
Nafsu makan menurun
(Dr. Rusdi Maslim, PPDGJ III)

MANIA
Trias Manic:
4. Flight of ideas
5. Euforia dan reaksi emosional yang labil, eksaltasi (perasaan senang dan
semangat yang ekstrim)
6. Sikap yang berubah-ubah dan tingkah laku yang hiperaktif
Nafsu bergerak yang banyak dan dapat terjadi logorhoe (bicara cepat dan
banyak)
Gejala tambahan:
3. Selalu bangga diri, sikap sombong, puas terhadap dirinya.
4. Kadang-kadang ada waham kebesaran.
Tanda
Penampilan Umum dan perilaku: agitasi psikomotor, menarik perhatian,
pakaian berwarna emarak,dadndanan berlebihan, kombinasi pakaian aneh,
intrusive, menghibur,mengancam,hipereksitasi.
Afek:labil, kuat
Mood: euforik, ekspansif, iritabel, menuntut,bercanda
Bicara;menekan, keras,dramatic, berlebihan dapat menjadi inkoheren
Isi pikiran: harga diri sangat tinggi,grandiositas, egosentrik tinggi,waham dan
lebih jarang halusinasi
Proses fikiran; flight of ideas(jika berat dpt menjadi inkoheren), pikiran
berpacu, neologisme,asosiasi bunyi(clang), sirkumstansial,
tangensial(mendadak berubah topic).
Sensorium: sangat mudah dialihkan, sulit konsentrasi.
Tilikan: sering terganggu.
Gejala
Perilaku keliru dan disinhibisi(semena-mena)
- Membuang uang berlebihan
- Berjudi berlebihan
- Hiperseksualitas, promiskusitas
Terlampau kepanjangan dalam aktivitas dan tanggung jawab
Toleransi frustasi rendah
Tanda vegetative
- Naiknya libido
- penurunanBB dan anoreksia
- Insomnia( diungkapkan sebagai tak perlu tidur)
- Energi berlebihan


EPISODE DEPRESIF GJALA KHAS/MENCOLOK
RINGAN Sekurang-kurangnya ada 2 dari 3 gjala
utama depresi
Ditambah sekurang-kurangnya 2 gjala
lainnya
tdk ada yg berat diantaranya
minimal berlangsung 2 minggu
Hanya sedikit kesulitan dlm pekerjaan
dan kegiatan social yang biasa
dilakukan
SEDANG Sekurang-kurangnya ada 2 dari 3
gjala utama depresi
Ditambah sekurang-kurangnya 3 (&
sebaiknya 4)dari gejala lainnya
minimal berlangsung 2 minggu
Menghadapi kesulitan nyata untuk
meneruskan keg.sosial,pekerjaan
dan urusan rumah tangga
BERAT tanpa Gjala Psikotik Semua 3 gjala utama depresi harus
ada
Ditambah sekurang-kurangnya 4
dari gjala lainnya, dan beberapa
diantaranya harus berintensitas
berat
berlangsung minimal 2 minggu
atau < bila gjala amat berat dan
beronset sangat ceoat
Sangat tdk mungkin pasient
mampu meneruskan
kegiatan
social,pekerjaan/urusan
rumah tangga kcuali pd taraf
yg sangat terbatas
BERAT dengan gjala Psikotik Sama sperti pd episode
depresif berat tanpa gjala
psikotik tapi disertai waham,
halusinasi atau stupor
depresif
waham biasnyamelibatkan
ide ttg
dosa,kemiskinan/malapetaka
yg mengancam dan pasien
merasa bertanggung jwb
atas itu smua.
halusinasi
auditorik/olfactorik berupa
suara yg
menghina/menuduh/bau
kotoran/daging membusuk

EPISODE MANIK GEJALA KHAS/MENONJOL
Hipomania Afek yang meninggi/berubah disertai
peningkatan aktifitas , menetap selama
sekurang-kurangnya beberapa hari
berturut-turut
Mania tanpa gejala psikotik Episode berlangsung sekurang-
kurangnya 1 minggu
Cukup berat sampai mengacaukan
seluruh pekerjaan atau hampir seluruh
aktifitas social yang biasa dilakukan
Aktifitas yang berlebihan,percepatan &
kbanyakan bicara,keb tdr yang
berkurang, Ide-ide perihal
kebesaran/grandiose ideasdan
terlaluoptimistik
Mania dengan Gejala psikotik Gmbrn klinisnya > berat dari mania tanpa gjala
psikotik
Harga diri yang membumbung dan gagasan
kebesaranwaham kebesaran
Iritabilitas & kecurigaan waham kejar (delusion
of persecution)
Waham & halusinasi sesuai dengan keadaan afek
tersebut (mood-congruent)


Perbedaan Klinis Antara Depresi dan Mania
No Pembeda Sindroma Depresif Sindroma Manik
1. Mood Depresi, iritabel,
atau cemas(tapi
pasien mungkin
tersenyum atau
menolak perubahan
mood subjektif dan
sebaliknya
mengeluhkan nyeri
atau keluhan
somatic lain)
Jeritan tangis (tapi
pasien dapat
mengeluh tak
mampu menangis
atau mengalami
emosi)
Elasi, iritabel, atau hostil
Menangis sejenak (sebagai
bagian keadaan campuran)
2. Manifestasi
psikologis
terkait
Tak punya
keyakinan diri,harga
diri rendah, sesal
diri,
Konsentrasi buruk ,
bimbang
Reduksi gratifikasi
,tdk ada minat
dalam aktivitas
lazimnya,lepas
kemelekatan, nyepi
dari pergaulan
Pengharapan
negate, putus asa,
tak berdaya,naiknya
ketergantungan
Rekurensi pikiran
Harga diri
berlebihan,membual,grandio
sitas
Pikiran brpacu,asosiasi clang(
pikiran baru dicetuskan oleh
bunyi ucapan bukan
artinya),mudah beralih
perhatian
Minat meninggi dalam
aktivitas teman, dan hal
kreatif baru, naiknya
keterlibatan dengan orang(
yang berselisih karena
perilaku pasien yang intrusive
dan ikut campur), pesta pora,
kebebasan seks,investas
bisnis bodoh.
akan mati dan
bunuh diri
3. Manifestasi
Somatik
Retardasi
psikomotor,
fatig,agitasi
Anoreksia, dan
penurunan BB, atau
penambahan BB
Insomnia, atau
hipersomnia
Ketidakteraturan
haid,amenore
Anhedonia,
hilangnya kehendak
seks

Akselerasi psikomotor,
eutonia(naiknya rasa
sejahtera fisik)
Kemungkinan penurunan BB
akibat naiknya aktifitas dan
inatensi pada kebiasaan diet
yang baik
Turunnya kebutuhan tidur
Naiknya nafsu seks
4. Gejala psikotik Delusi tak berharga
dan berdosa
Delusi rujukan dan
persekusi
Delusi diri sakit
(nihilistic,somatic,at
au hipokondriak)
Delusi kemiskinan
Halusinasi depresif
dibidang
auditorik,visual, dan
(sangat jarang)
olfaktorius
Delusi grandiose akan bakat
istimewa
Delusi bantuan,delusi rujukan
dan persekusi
Delusi kebugaran mental dan
fisik istimewa
Delusi kaya,keturunan
bangsawan atau identitas
gradios lain
Halusinasi visual atau
auditorik sekilas

(Buku Saku Psikiatri Klinik, Harold I Kaplan & Benajmin J Sadock)

9. Apa macam-macam mood dan afektif?
Mood: tonus perasaan, khususnya yang dialami secara internal oleh seseorang.
mood kongruen(serasi dengan afek) =mood apropriat=ide konsisten dengan
moodsering pada gangguan bipolar
mood inkongruen (tidak serasi dengan afek) =mood inapropriat=ide tak
selaras dengan mood sering pada skizofrenia
Macam Mood
Eutimik: mood dlm batas normal, tdk tertekan atau melambung
Disforik: mood yg tdk menyenagkan
Elevated: lebih ceria dari biasanya
Iritable: mudah diganggu/dibuat marah
Euforia: elasi kuat dg perasaan kebesaran
Ecstasy: rasa kegembiraan yg kuat dan luarbiasa
Expansive: perasaan meluap-luap tanpa batas
Anhedonia: hilang minat, menarik diri dari aktivitas rutin yg menyenangkan
Aleksitimia: kesulitan / tdk mampu menggambarkan emosi / mood

Afek: tonus perasaan subyektif yang menyertai suatu idea tau representasi mental;
unsure perilaku objektif diungkapkan sebagai tumpul (menurun berat), datar(absen),
restriksi(menurun), apropriat(serasi), inapropriat(tidak serasi), dan labil(tak stabil)
Macam Afek
Afek sesuai (appropriate affect): irama perasaan harmonis dg pikiran dan
pembicaraan, rentang emosi lengkap/luas diekspresikan scr sesuai
Afek tdk sesuai (inappropriate affect): irama perasaan tdk harmonis dg
pikiran dan pembicaraan
Afek terbatas (restricted or constricted affect): penurunan irama perasaan
kurang parah
Afek tumpul (blanted affect): penurunan berat pd intensitas irama perasaan
Afek datar (flat affect): hampir tdk ada tdk ada tanda ekspresi afek, suara
monoton wajah kosong tdk ada gerakan
Afek labil (labile affect): perubahan irama perasaan yg cepat dan tiba-tiba yg
tdk berhubungan dg situasi eksternal

10. Apa macam macam dari gangguan mood/afektif?
Suatu kelompok kondisi klinis yang ditandai oleh hilangnya perasaan kendali dan
pengalaman subjektif adanya penderitaan berat.
Dua gangguan mood utama adalah gangguan depresif berat dan gangguan bipolar I.
Menurut DSM-IV:
Depresi berat (depresi unipolar)
Ggn bipolar:
Episode mani-depresi atau mani-mani (mani unipolar atau mani murni)
Episode hipomani-depresi
Ggn mood tambahan:
Ggn siklotimik (siklotimia)
Ggn distimik (distimia)
Ggn berhubungan dg sindrom depresi:
Ggn depresi ringan sedang
Ggn depresi singkat rekuren ( berat-ringan)
Ggn disforik pra menstrual
Ggn mood krn kondisi medis umum
Ggn mood akibat zat
Ggn mood yg tdk ditentukan



Mood meninggi Mania : mood meluap-luap, peningkatan harga diri, gagasan
meloncat-loncat (flight of ideas), gagasan kebesaran, hiperaktif, kurang tidur.
Mood terdepresi Depresi : kurang/hilang energi dan minat, nafsu makan,
perasaan bersalah, sulit konsentrasi, pikiran kematian/bunuh diri.
(Sinopsis Psikiatri Jilid I, Kaplan dan Sadock)

F30 EPISODE MANIK
F30.1 Hipomania
F30.2 Mania Tanpa Gejala Psikotik
F30.3 Mania Dengan Gejala Psikotik
F30.8 Episode Manik Lainnya
F30.9 Episode Manik YTT
F32 EPISODE DEPRESIF
F32.0 Episode Depresif Ringan
F32.00 Tanpa Gejala Somatik
F32.01 Dengan Gejala Somatik
F32.1 Episode Depresif Sedang
F32.00 Tanpa Gejala Somatik
F32.01 Dengan Gejala Somatik
F32.2 Episode Depresif Berat Tanpa Gejala Psikotik
F32.3 Episode Depresif Berat Dengan Gejala Psikotik
F32.8 Episode Depresif Lainnya
F32.9 Episode Depresif YTT
F31.0 Gangguan afektif bipolar, episode kini hipomanik
F31.1 Gangguan afektif bipolar, episode kini manik tanpa gejala psikotik
F31.2 Gangguan afektif bipolar, episode kini manik dengan gejala psikotik
F31.3 Gangguan afektif bipolar, episode kini depresif ringan atau sedang
F31.4 Gangguan afektif bipolar, episode kini depresif berat tanpa gejala psikotik
F31.5 Gangguan afektif bipolar, episode kini depresif berat dengan gejala psikotik
F31.6 Gangguan afektif bipolar, episode kini campuran
F31.7 Gangguan afektif bipolar, kini dalam remisi
F31.8 Gangguan afektif bipolar lainnya
F31.9 Gangguan afektif bipolar yang tidak tergolongkan
(Dr. Rusdi Maslim, PPDGJ III)


1. Etiologi gangguan mood
< Faktor Biologis
Norepinefrin
- aktivitas reseptor adrenergik-alfa2 penurunan jumlah
norepinefrin yg dilepaskan
- penurunan serotonin mencetuskan depresi ( beberapa pasien
bunuh diri memiliki konsentrasi metabolit serotonin di dalam cairan
serebrospinal yang rendah )
Dopamin
- aktivitas dopamin menurun pasien depresi
- aktivitas dopamin meningkat pasien mania
- jalur dopamin mesolimbik mungkin mengalami disfungsi pada
depresi. Reseptor dopamin tipe 1 ( D1 ) mungkin hipoaktif pada
depresif
Faktor Neurokimiawi lain.
- Neurotransmiter asam amino, khususnya gamma-aminobutyric acid
(GABA)dan peptida neuroaktif (khususnya vasopresin dan opiat
endogen) => patofisiologi gangguan mood.
- Beberapa peneliti telah menyatakan bahwa sistem pembawa kedua
(second-messenger), seperti: adenylate cyclase,
phosphotidylinositol, dan regulasi kalsiumjuga memiliki relevansi
penyebab.
Regulasi neuroendokrin.
- Hipotalamus sebagai pusat regulasi sumbu neurohormonal dan
hipotalamus menerima banyak masukan (input) neuronal yang
menggunakan neurotransmiter amin biogenik.
- Sumbu neuroendokrin utama ggn mood adalah: sumbu adrenal,
tiroid, dan hormon pertumbuhan.
- Kelainan neuroendakrin lainnya adalah sekresi nokturnal
melantonin, pelepasan prolaktin terhadap pemberian
tryptophan, kadar follicle-stimulating hormone (FSH) dan
luteinzing hormone (LH), dan testosteron pada laki-laki.
< Faktor Genetik
Penelitian keluarga
- saudara derajat pertama penderita ggn bipolar I => 8 - 18 kali >
saudara derajat pertatma subjek kontrol untuk menderita
gangguan bipolar I & 2-10 kali lebih menderita ggn depresif berat.
- saudara derajat pertama penderita ggn depresif berat => 1,5-2,5
kali > saudara derajat pertama subjek kontrol untuk menderita
gangguan bipolar I dan 2-3 kali lebih mungkin menderita gangguan
depresif berat.
Penelitian adopsi
- Anak biologis dari orang tua yg menderita, berada dlm risiko
menderita ggn mood, bahkan jika dibesarkan oleh keluarga angkat
yg tidak menderita gangguan.
Penelitian kembar
- Anak kembar menunjukkan bahwa angka kesesuaian untuk
gangguan bipolar I pada kembar monozigotik adalah 33-90 %,
untuk ggn depresif berat angka adalah 50 %.
- Sebaliknya, angka kesesuaian pada kembar dizigotik adalah 5-25 %
untuk ggn bipolar I dan 10-25 % untuk ggn depresif berat.
< Faktor Psikososial
Peristiwa kehidupan dan stres lingkungan.
Peristiwa kehidupan (clefts) melepaskan corticotropin-releasing hormone (CRH),
menstimulasi pelepasan hormon adrenokortikotropik (ACTH) dari hipofisis
anterior. ACTH => pelepasan kortisol dari korteks adrenal. Kortisol memberikan
umpan batik (feed back) pada jaringan kerja melalui sekurangnya dua
mekanisme:
mekanisme umpan balik cepat, peka terhadap kecepatan peningkatan
konsentrasi kortisol, beroperasi melalui reseptor kortisol di hipokampus
dan menyebabkan pelepasan ACTH;
mekanisme umpan balik lambat, sensitif terhadap konsentrasi kortisol,
bekerja melalui reseptor hipofisis dan adrenal.
< Faktor Pramorbid
Tipe kepribadian: dependen, obsesif-kompulsif, histeriakal risiko > ggn depresi
daripada tipe kepribadian antisocial, paranoid, dan lainnya yang menggunakan
proyeksi dan mekanisme pertahanan mengeksternalisasikan lainnya.
(Sinopsis Psikiatri Jilid I, Kaplan dan Sadock)

11. Apa penyebab dari gangguan afektif?

12. Bagaimana cara menilai scoring GAF?
DEPRESI
Teori interpersonal. Asumsi dari teori ini adalah bahwa individu yang depresi
cenderung memiliki hubungan sosial yang kurang baik dan mengganggap mereka
kurangmemberikan dukungan. Sedikitnya dukungan sosial dapat mengurangi
kemampuan individu untuk mengatasi peristiwa hidup yang negatif dan membuat
mereka rentan terhadap depresi.

SKOR GAF
100-91 : Gejala tidak ada, berfungsi maksimal, tidak ada masalah yang tak
tertanggulangi
90-81 : Gejala minimal, berfungsi baik, cukup puas, tidak lebih dari masalah harian
yang biasa
80-71 : gejala sementara dan dapat diatasi, disabilitas ringan dalam social,
pekerjaan, sekolah, dll.
70-61 : beberapa gejala ringan dan menetap, disabilitas ringan dalam fungsi,
secara umum masih baik.
60-51 : gejala sedang ( moderate), disabilitas sedang
50-41 : gejala berat (serious), disabilitas berat
40-31 : beberapa disabilitas dalam hubungan dengan realita dan komunikasi,
disabilitas berat dalam beberapa fungsi
30-21 : disabilitas berat dalam komunikasi dan daya nilai, tidak mampu berfungsi
hamper semua bidang
20-11 : bahaya mencederai diri / orang lain, disabilitas sangat berat dalam
komunikasi dan mengurus diri
10-01 : seperti di atas persisten dan lebih serius
0 : informasi tidak adekuat

1 . MA S L I M R. . B U K U S A K U DI A G N O S I S GA N G G U A N J I WA : RU J U K A N
RI N G K A S D A R I P P DGJ I I I . J A K A R T A .
2 . KA P L A N D A N S A D O C K , . S I N O P S I S P S I K I A T R I , E D I S I K E T U J U H .
B I N A R U P A AK S A R A , J A K A R T A .

13. Apa terapi yang diberikan pada pasien ini?
Terapi Psikososial
Tiga jenis psikoterapi jangka pendek :
- terapi kognitif
- terapi interpersonal
- terapi perilaku.
Bermanfaat: gangguan depresif berat.
Psikoterapi berorientasi psikoanalitik
Terapi kognitif, pada distorsi kognitif pada depresif berat.
Tujuan terapi kognitif adalah menghilangkan episode depresif dan
mencegah rekurennya dengan membantu pasien mengidentifikas dan uji
kognitif negatif; mengembangkan cara berpikir altenatif, fleksibel, dan
positif; dan melatih kembali respon kognitif dan perilaku yang baru.
Terapi interpersonal
Memusatkan pada satu atau dua masalah interpersonal pasien yang sedang
dialami sekarang,
Pertama, masalah interpersonal sekarang kemungkinan memiliki hubungan
awal yang disfungsional.
Kedua, masalah interpersonal sekarang adalah efektif di dalam pengobatan
gangguan depresif berat dan mungkin, secara spesifik membantu menjawab
masalah.
Terapi berorientasi psikoanalitik.
Pendekatan psikoanalitik pada teori psikoanalitik tentang depresi dan mania.
Tujuan umum
= perubahan struktur atau karakter, bukan semata-mata menghilangkan
gejala.
= perbaikan kepercayaan diri, keakraban, mekanisme mengatasi, kapasitas
berdukacita, dan kemampuan untuk mengalami berbagai macam emosi
Terapi keluarga
Indikasi
= jika gangguan membahayakan perkawinan atau fungsi keluarga
= jika gangguan mood adalah diperkembangkan atau dipertahankan oleh
situasi keluarga
Farmakoterapi
Indikasi
Gangguan depresif berat.
= obat trisiklik. masalah pasien tidak respon terhadap pengobatan
pertama;
semua antidepresan memerlukan waktu 3-4 minggu efek terapetik,
semua antidepresan memiliki efek merugikan.
Tetapi,
= bupropion (Wellbutrin)
= serotoninspecific reuptake inhibitors (SSRIs): fluoxetine, paroxetin,
dan setraline (Zoloft)klinis lebih aman dan lebih baik ditoleransi
daripada obat yang sebelunnya, sama efektifnya.
gejala pertama yang membaik adalah pola tidur dan makan yang
terganggu.agitasi, kecemasan, episode depresif.
gejala selanjutnya yang membaik: energi yang rendah, konsentrasi yang
buruk, ketidakberdayaan, dan penurunan libido
PENDIDIKAN PASIEN.
tentang penggunaan antidepresan adalah sama pentingnya bagi keberhasilan
pengobatan.
bahwa pasien tidak akan mengalami ketagihan terhadap antidepresan,
diperlukan waktu 3-4 minggu untuk dapat dirasakannya efek antidepresan:,
menjelaskan efek samping secara terinci;
mempertimbangkan risiko hunuh diri
ALTERNATIF TERHADAP TERAPI OBAT.
elektrokonvulsif terapi dan fototerapi.
elektrokonvulsif terapi (ECT) digunakan jika
(1) pasien tidak responsif terhadap farmakoterapi,
(2) pasien tidak dapat mentoleransi farmakoterapi, atau
(3) situasi klinis adalah sangat parah sehingga diperlukan perbaikan cepat.
Fototerapi adalah suatu pengobatan baru pada pasien ggn mood dgn pola
musiman, dapat digunakan sendiri dan kombinasi
Obat trisiklik, dan tetrasiklik
monoamine oxidase inhibitors (MAOIs).
serotonin specific reuptake inhibitors (SSRIs) dan
Antidepresan atipikal lain: bupropion, trazodone (Desyrel) dan alprazolam
(Xanax)
(Sinopsis Psikiatri, Kaplan & Sadock ed. 7 jilid satu)

Terapi Psikologik
Psikoterapi suportif selalu diindikasikan.
Berikan kehangatan, empati, pengertian dan opimistik.
Bantu pasien mengidentifikasi dan mengekspresikan hal-hal yang membuatnya
prihatin dan melontarkannya.
Bantulah memecahkan problem eksternal (misal, pekerjaan, menyewa rumah)-
arahkan pasien, terutama selama episode akut dan bila pasien aktif bergerak.
Latih pasien untuk mengenal tanda-tanda dekompesasi yang akan datang
Temui pasien sesering mungkin (mula-mula 1-3 kali per minggu) dan secara
teratur tetapi jangan sampai tidak berakhir atau untk selamanya.
Kenalilah bahwa beberapa pasien depresi dapat memprovokasi kemarahan anda
(melalui kemarahan, hostilitas, dan tuntutan yang tak masuk akal, dll)
Psikoterapi berorientasi tilikan jangka panjang dapat berguna pada pasien
depresi minor kronis tertentu dan beberapa pasien dengan depresi mayor yang
mengalami remisi tetapi mempunyai konflik.
Terapi kognitif perilaku dapat sangat bermanfaat pada pasien depresi sedang dan
ringan
Depresi diterapi dengan memberikan pasien latihan keterampilan dan
pengelaman -pengalaman sukses.
Dari perspektif kognitif, pasien dilatih untuk mengenal dan menghilangkan pikian
-pikiran negatif dan harapan harapan negatif. Terapi ini mencegah
kekambuhan.
Deprivasi tidur parsial (bangun mulai di pertengahan malam dan tetap terjaga
sampai malam berikutnya), dapa membantu mengurangi gejala gejala depresi
mayor buat sementara.
Latihan fisik (berlari,berenang) dapat memperbaiki depresi, dengan mekanisme
bilologik yang belum dimengerti dengan baik.


Terapi Fisik
- Litium efektif dalam membuat remisi gangguan bipolar, mania dan mungkin
bermanfaat dalam pengobatan depresi bipolar akut dan beberapa depresi
unipolar.
- Antikonvulsan juga sama baik dengan litium untuk mengobati kondisi akut,
meskipun kurang efektif untuk rumatan. Antidepresan dan litium dapat
dimulai bersama sama dan litium diteruskan setelah remisi.
- Antipsikotik diperlukan bagi pasien psikotik, paranoid, atau pasien yang
sangat agitasi, tunggal atau bersama sama dengan antidepresan,
litium, atau ECT-anti depresan yang baru juga terlihat efektif.
ECT mungkin merupakan terapi terpilih :
bila obat tidak berhasil setelah satu atau lebih dari 6 minggu pengobatan,
bila kondisi pasien menuntut remisi segera (misal, bunuh diri yang akut)
pada beberapa depresi psikotik
pada pasien yang tak dapat mentoleransi obat (misal, pasien tua yang
berpenyakit jantung). Lebih dari 90% pasien memberikan respons.
(Buku Saku Psikiatri, David A tomb)
Indikasi utama untuk antidepresan adalah episode depresif berat
Obat lini pertamatrisiklik atau tetrasiklik atau SSRI
Alogaritma untuk mengobati pasien dengan gangguan depresif berat


Obat Anti Depresi ( Thymoleptics, Psychic Energizers, Anti Depressants, Anti
Depresan
+ Penggolongan
B. Golongan Obat pada Gangguan Depresi
C.
D. Diagram skematis titik tangkap obat-obat antidepresan
E.
F. SUMBER: B G KATZUNG, BASI C CLI NI CAL PHARMACOLOGY 10TH ED, 2006.
+ Indikasi
Untuk Sindroma Depresi

+ Kontraindikasi
Penyakit jantung koroner, MCI, khususnya pd usia lanjut
Glaukoma, Retensi Urin, Hipertrofi Prostat, Gg fungsi hati, Epilepsi
Pd penggunaan obat Lithium, kelainan fungsi jantung, ginjal dan kelenjar
thyroid
Wanita hamil dan menyusui tdk dianjuran menggunaan TCA, resiko
teratogenik besar ( khususnya trimester 1 ) dan TCA diekskresi mll ASI

+ Mekanisme Kerja
Menghambat re uptake aminergik neurotransmitter (Noradrenalin,
serotonin, dopamin) dan menghambat penghancuran oleh
enzim MAO ( Monoamine Oxidase ) shg terjadi peningkatan jumlah aminergik
neurotrasmitter pada sinaps neuron di SSP.

+ Dosis
Yg perlu dipertimbangkan :
Onset efek primer : sekitar 2 4 minggu
Onset efek sekunder : sekitar 12 24 jam
Waktu paruh : 12 48 jam ( pemberian 1 2 x / hari )
Ada 5 proses dlm pengaturan dosis :
Initiating Dosage ( test dose) untuk mencapai dosis anjuran selama
mgg I
Titrating Dosage ( optimal dose ) mulai dosis anjuran sampai mencapai
dosis efektif dosis optimal
Stabilizing Dosage ( Stabilizing dose ) dosis optimal dipertahankan
selama 2 3 bulan
Maintaining Dosage ( Maintaining dose ) selama 3 6 bulan. Biasanya
dosis pemeliharaan = dosis optimal
Tapering Dosage ( tapering dose ) selama 1 bulan. Kebalikan dari
proses Initiating Dosage

+ Efek Samping
Sedasi ( rasa mengantuk, kewaspadaan berkurang, kinerja psikomotor
menurun, kemampuan kognitif menurun, dll )
Efek Antikolinergik ( mulut kering, retensi urin, penglihatan kabur, konstipasi,
sinus tekikardia, dll )
Efek Anti adrenergik alfa ( perubahan EKG, hipotensi )
Efek Neurotoksis ( tremor halus, gelisah, agitasi, insomnia )

+ Cara mengatasinya :
Gastric lavage ( hemodialisis tdk bermanfaat oleh karena obat Trisiklik
bersifat protein binding forced diuresis juga tdk bermanfaat oleh karena
renal excretion of free drug rendah )
Diazepam 10 mg ( im ) untuk mengatasi konvulsi
Prostigmine 0,5 1,0 mg ( im ) untuk mengatasi efek anti kolinergik ( dp
diulangi setiap 30 45 sampai gejala mereda )
Monitoring EKG untuk deteksi kelainan jantung
(Maslim, Rusdi, Panduan Praktis Penggunaan Klinis Obat Psikotropik, 2001, Edisi
ke-3)