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Mood Disorders               Depression and Bipolar Disorder   Mood:        Pervasive and sustained feeling tone that is ...
Mood Disorders             Hypomania is an episode of manic symptoms that does not meet the full              (DSM-IV-TR)...
Mood Disorders            II. DSM-IV-TR Classification of Mood Disorders i. Depression   According to DSM-IV-TR:    A maj...
Mood Disorders     Dysthymic disorder are characterized by at least 2 years of depressed mood that is      not sufficient...
Mood Disorders              Table 15.1-1 Lifetime Prevalence Rates of Depressive Disorders:                           Type...
Mood Disorders            3) Women also have a higher rate of being rapid cyclers "four or more manic               episod...
Mood Disorders     o In both unipolar and bipolar disorder, men more frequently present with substance       use disorders...
Mood Disorders              o Other evidence is the role of the presynaptic β2-receptors in depression,                bec...
Mood Disorders                Cholinergic neurons have interactive relationships with all three                 monoamine...
Mood Disorders    b) Second Messengers and Intracellular Cascades         The binding of a neurotransmitter to the postsy...
Mood Disorders                  Tested by administration of dexamethasone (Decadron) (0.5 to 2.0 mg),                   a...
Mood Disorders                  ­ Prolactin is released from the pituitary by serotonin stimulation and                   ...
Mood Disorders    e) Immunological Disturbance             ­ Depressive disorders are associated with several immunologica...
Mood Disorders                   Again, evidence suggests that antidepressants at least partially normalize              ...
Mood Disorders                  The former subdivision shares extensive connections with other limbic                   r...
Mood Disorders     B. Adoption Studies:              Adoption studies provide an alternative approach to separating genet...
Mood Disorders             o Another study has reported evidence for a gene-environment interaction in               the d...
Mood Disorders         As a result, a person has a high risk of undergoing subsequent episodes of a          mood disorde...
Mood Disorders                That theory involves four key points:                  a) Disturbances in the infant-mother...
Mood Disorders   D. Psychodynamic Factors in Mania:         Most theories of mania view manic episodes as a defense again...
Mood Disorders           learned that outcomes were independent of responses, so they had both           cognitive motivat...
Mood Disorders                                           Diagnosis  In addition to the diagnostic criteria for major depre...
Mood Disorders   D. The symptoms are not due to the direct physiological effects of a substance (e.g., a      drug of abus...
Mood Disorders      If the full criteria are currently met for a major depressive episode, specify its    current clinical...
Mood Disorders     Note: This exclusion does not apply if all of the manic-like, mixed-like, or     hypomanic-like episode...
Mood Disorders       ­ According to DSM-IV-TR, patients must be experiencing their first manic         episode to meet the...
Mood Disorders Table 15.1-15 DSM-IV-TR Diagnostic Criteria for Bipolar I Disorder, Most Recent                            ...
Mood Disorders Table 15.1-17 DSM-IV-TR Diagnostic Criteria for Bipolar I Disorder, Most Recent                            ...
Mood Disorders      (e.g., hyperthyroidism). Note: Mixed-like episodes that are clearly caused by somatic antidepressant t...
Mood Disorders     schizophreniform disorder, delusional disorder, or psychotic disorder not otherwise     specified.  E. ...
Mood Disorders              7. excessive involvement in pleasurable activities that have a high potential                 ...
Mood Disorders major depressive episode (only if it is the most recent type of mood episode):    In partial remission, in...
Mood Disorders              The following factors are associated with a poor prognosis for patients with               mo...
Mood Disorders      2. lack of reactivity to usually pleasurable stimuli (does not feel much better, even         temporar...
Mood Disorders recent 2 years of dysthymic disorder; if the major depressive episode is not current, it applies if the fea...
Mood Disorders    2. excessive motor activity (that is apparently purposeless and not influenced by external       stimuli...
Mood Disorders can be applied only if the criteria are currently met for a major depressive episode. In partial remission ...
Mood Disorders      o Mood-congruent psychotic features: Delusions or hallucinations whose content        is entirely cons...
Mood DisordersN.B.2: Describing Course of Recurrent Episodes:    o The DSM-IV-TR includes criteria for three distinct cour...
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
Mood Disorders For Post-graduates
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Mood Disorders For Post-graduates

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Mood Disorders For Post-graduates

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  1. 1. Mood Disorders Depression and Bipolar Disorder Mood:  Pervasive and sustained feeling tone that is experienced internally and influences a persons behavior and perception of the world.  Mood can be normal, elevated, or depressed. Affect: o The external expression of mood. Mood disorders o Group of clinical conditions characterized by a loss of sense of control and a subjective experience of great distress. o Patients with elevated mood demonstrate expansiveness, flight of ideas, decreased sleep, and grandiose ideas. o Patients with depressed mood experience a loss of energy and interest, feelings of guilt, difficulty in concentrating, loss of appetite, and thoughts of death or suicide. o Other signs and symptoms of mood disorders include change in activity level, cognitive abilities, speech, and vegetative functions (e.g., sleep, appetite, sexual activity, and other biological rhythms). o These disorders virtually always result in impaired interpersonal, social, and occupational functioning. N.B.: ­ It is tempting to consider disorders of mood on a continuum with normal variations in mood. ­ However, patients with mood disorders often report an ineffable ‫ ,ﯾﻔ ﻮق اﻟﻮﺻ ﻒ‬but distinct, quality to their pathological state. ­ Therefore, the concept of a continuum may represent the clinicians overidentification with the pathology, thus possibly distorting his or her approach to patients with mood disorder. ­ Patients afflicted with only major depressive episodes are said to have major depressive disorder or unipolar depression. ­ Patients with both manic and depressive episodes or patients with manic episodes alone are said to have bipolar disorder. ­ The terms "unipolar mania" and "pure mania" are sometimes used for patients who are bipolar, but who do not have depressive episodes. ­ Three additional categories of mood disorders are hypomania, cyclothymia, and dysthymia :- 1 -Page By Mohamed Abdelghani
  2. 2. Mood Disorders  Hypomania is an episode of manic symptoms that does not meet the full (DSM-IV-TR) criteria for manic episode.  Cyclothymia and dysthymia are defined by DSM-IV-TR as disorders that represent less severe forms of bipolar disorder and major depression, respectively. ­ The field of psychiatry has considered major depression and bipolar disorder to be two separate disorders, particularly in the last 20 years. ­ However, the possibility that bipolar disorder is actually a more severe expression of major depression is reconsidered recently. ­ Many patients given a diagnosis of a major depressive disorder reveal, on careful examination, past episodes of manic or hypomanic behavior that have gone undetected. ­ Many authorities see considerable continuity between recurrent depressive and bipolar disorders. ­ This has led to widespread discussion about the bipolar spectrum, which incorporates classic bipolar disorder, bipolar II, and recurrent depressions. I. History The Old Testament story of King Saul describes a depressive syndrome, as does thestory of Ajaxs suicide in Homers Iliad. About 400 BCE, Hippocrates used the terms mania and melancholia to describe mentaldisturbances. Around 30 AD, the Roman physician Celsus described melancholia (from Greek melan"black" and chole "bile") in his work De re medicina as a depression caused by black bile. In 1854, Jules Falret described a condition called folie circulaire, in which patientsexperience alternating moods of depression and mania. In 1882, the German psychiatrist Karl Kahlbaum, using the term cyclothymia,described mania and depression as stages of the same illness. In 1899, Emil Kraepelin described manic-depressive psychosis using most of thecriteria that psychiatrists now use to establish a diagnosis of bipolar I disorder. According to Kraepelin, the absence of a dementing and deteriorating course in manic-depressive psychosis differentiated it from dementia praecox (as schizophrenia was thencalled). Kraepelin also described a depression as involutional melancholia, which was viewedas a form of mood disorder that begins in late adulthood.- 2 -Page By Mohamed Abdelghani
  3. 3. Mood Disorders II. DSM-IV-TR Classification of Mood Disorders i. Depression According to DSM-IV-TR:  A major depressive disorder occurs without a history of a manic, mixed, or hypomanic episode.  A major depressive episode must last at least 2 weeks.  Typically a person with a major depressive episode also experiences at least four symptoms from a list that includes changes in appetite and weight, changes in sleep and activity, lack of energy, feelings of guilt, problems thinking and making decisions, and recurring thoughts of death or suicide.ii. Mania & Hypomania A manic episode is a distinct period of an abnormally and persistently elevated,expansive, or irritable mood lasting for at least 1 week, or less if a patient must behospitalized. A hypomanic episode lasts at least 4 days and is similar to a manic episode except thatit is not sufficiently severe to cause impairment in social or occupational functioning, andno psychotic features are present. Both mania and hypomania are associated with inflated self-esteem, decreased need forsleep, distractibility, great physical and mental activity, and overinvolvement inpleasurable behavior.iii. Bipolar I disorder According to DSM-IV-TR:  Bipolar I disorder is defined as having a clinical course of one or more manic episodes and, sometimes, major depressive episodes.  A mixed episode is a period of at least 1 week in which both a manic episode and a major depressive episode occur almost daily.  A variant of bipolar disorder characterized by episodes of major depression and hypomania rather than mania is known as bipolar II disorder.iv. Dysthymia and Cyclothymia Dysthymic disorder and cyclothymic disorder are characterized by the presence ofsymptoms that are less severe than those of major depressive disorder and bipolar Idisorder, respectively.- 3 -Page By Mohamed Abdelghani
  4. 4. Mood Disorders  Dysthymic disorder are characterized by at least 2 years of depressed mood that is not sufficiently severe to fit the diagnosis of major depressive episode.  Cyclothymic disorder is characterized by at least 2 years of frequently occurring hypomanic symptoms that cannot fit the diagnosis of manic episode and of depressive symptoms that cannot fit the diagnosis of major depressive episode.v. Other Categories  The DSM-IV-TR includes three mood disorder research categories (minor depressive disorder, recurrent brief depressive disorder, and premenstrual dysphoric disorder).  Other DSM-IV-TR diagnoses are mood disorder due to a general medical condition and substance-induced mood disorder.  Finally, DSM-IV-TR includes three residual disorders: bipolar disorder NOS, depressive disorder NOS, and mood disorder NOS. III. Epidemiology1) Incidence and Prevalence o Mood disorders are common. o Major depressive disorder has the highest lifetime prevalence (almost 17%) of any psychiatric disorder. o The lifetime prevalence rate of different forms of DSM-IV-TR unipolar depressive disorder are shown in Table 15.1-1. o The lifetime prevalence rate of different clinical forms of bipolar disorder are shown in Table 15.1-2. o The annual incidence (number of new cases) of a major depressive episode is 1.59% (women, 1.89%; men, 1.10%). o The annual incidence of bipolar illness is less than 1%, but it is difficult to estimate, because milder forms of bipolar disorder are often missed.- 4 -Page By Mohamed Abdelghani
  5. 5. Mood Disorders Table 15.1-1 Lifetime Prevalence Rates of Depressive Disorders: Type Lifetime Prevalence (%) Range 5:17 Major depressive episode Average 12 Range 3:6 Dysthymic disorder Average 5 Range 10 Minor depressive disorder Average Range 16 Recurrent brief depressive disorder Average Full unipolar spectrum 20:25 Table 15.1-2 Lifetime Prevalence Rates of Bipolar I, Bipolar II, Cyclothymic Disorder, and Hypomania: Type Lifetime Prevalence (%) Bipolar I disorder 0: 2.4 Bipolar II disorder 0.3: 4.8 Cyclothymia 0.5: 6.3 Hypomania 2.6: 7.8 Full bipolar spectrum 2.6: 7.82) Sex  Major depressive disorder has twofold greater prevalence in women than in men.  This may be due to:  Hormonal differences  The effects of childbirth  Differing psychosocial stressors for women and for men  Behavioral models of learned helplessness  Bipolar I disorder has an equal prevalence among men and women, however: 1) Manic episodes are more common in men, and depressive episodes are more common in women. 2) When manic episodes occur in women, they are more likely than men to present a mixed picture (e.g., mania and depression).- 5 -Page By Mohamed Abdelghani
  6. 6. Mood Disorders 3) Women also have a higher rate of being rapid cyclers "four or more manic episodes in a 1-year period".3) Age  The onset of bipolar I disorder is earlier than that of major depressive disorder.  The age of onset for bipolar I disorder ranges from childhood (age 5 or 6) to 50 years or even older in rare cases, with a mean age of 30.  The mean age of onset for major depressive disorder is about 40 years, with 50% of all patients having an onset between the ages of 20 and 50.  Major depressive disorder can also begin in childhood or in old age.  Recent epidemiological data suggest that the incidence of major depressive disorder may be increasing among people younger than 20 years of age. This may be related to the increased use of alcohol and drugs of abuse in this age group.4) Marital Status o Major depressive disorder occurs most often in persons with poor interpersonal relationships or in those who are divorced or separated. o Bipolar I disorder is more common in divorced and single persons than among married persons, but this difference may reflect the early onset and the resulting marital discord characteristic of the disorder.5) Socioeconomic and Cultural Factors  No correlation was found between socioeconomic status and major depressive disorder.  A higher than average incidence of bipolar I disorder is found among the upper socioeconomic groups.  Bipolar I disorder is more common in persons who did not graduate from college than in college graduates, which may also reflect the relatively early age of onset for the disorder.  Depression is more common in rural areas than in urban areas.  The prevalence of mood disorder does not differ among races.6) Comorbidity o Individuals with major mood disorders are at an increased risk of having one or more additional comorbid Axis I disorders. o The most frequent disorders are alcohol abuse or dependence, panic disorder, OCD, and social anxiety disorder. o Conversely, individuals with substance use disorders and anxiety disorders also have an elevated risk of lifetime or current comorbid mood disorder.- 6 -Page By Mohamed Abdelghani
  7. 7. Mood Disorders o In both unipolar and bipolar disorder, men more frequently present with substance use disorders, whereas women more frequently present with comorbid anxiety and eating disorders. o In general, patients who are bipolar more frequently show comorbidity of substance use and anxiety disorders than do patients with unipolar major depression. In the Epidemiological Catchment Area (ECA) study, the lifetime history of substance use disorders, panic disorder, and OCD was approximately twice as high among patients with bipolar I disorder than in patients with unipolar major depression. o Comorbid substance use disorders and anxiety disorders worsen the prognosis of the illness and markedly increase the risk of suicide among patients who are unipolar major depressive and bipolar. IV. Etiologyi. Biological Factors ­ Until recently, the monoamine neurotransmitters (norepinephrine, dopamine, serotonin, and histamine) were the main focus of theories and research about the etiology of these disorders. ­ A progressive shift has occurred from focusing on disturbances of single neurotransmitter systems in favor of studying neurobehavioral systems, neural circuits, and more intricate neuroregulatory mechanisms. ­ Thus, the monoaminergic systems are now viewed as neuromodulary systems and disturbances are as likely to be secondary or epiphenomenal effects as they are directly related to etiology and pathogenesis. a) Biogenic Amines ­ Of the biogenic amines, norepinephrine and serotonin are the two neurotransmitters most implicated in the pathophysiology of mood disorders. 1) Norepinephrine o The correlation between the downregulation or decreased sensitivity of β- adrenergic receptors and clinical antidepressant responses is probably the most compelling data indicating a direct role for the noradrenergic system in depression.- 7 -Page By Mohamed Abdelghani
  8. 8. Mood Disorders o Other evidence is the role of the presynaptic β2-receptors in depression, because activation of these receptors results in a decrease of the amount of norepinephrine released. o Presynaptic β2-receptors are also located on serotonergic neurons and regulate the amount of serotonin released. o The clinical effectiveness of antidepressant drugs with noradrenergic effects "e.g., venlafaxine (Effexor)" further supports a role for norepinephrine in the pathophysiology of at least some of the symptoms of depression. 2) Serotonin  With the huge effect that SSRIs "e.g., fluoxetine (Prozac)" have made on the treatment of depression, serotonin has become the biogenic amine neurotransmitter most commonly associated with depression.  Other data indicate that serotonin is involved in the pathophysiology of depression: 1. Depletion of serotonin may precipitate depression. 2. Some patients with suicidal impulses have low cerebrospinal fluid (CSF) concentrations of serotonin metabolites and low concentrations of serotonin uptake sites on platelets. 3) Dopamine  The data suggest that dopamine activity may be reduced in depression and increased in mania.  Drugs that reduce dopamine concentrations "e.g., reserpine (Serpasil)" and diseases that reduce dopamine concentrations (e.g., Parkinsons disease) are associated with depressive symptoms.  In contrast, drugs that increase dopamine concentrations, such as tyrosine, amphetamine, and bupropion (Wellbutrin), reduce the symptoms of depression.  Two recent theories about dopamine and depression are: a. The mesolimbic dopamine pathway may be dysfunctional in depression. b.The dopamine D1 receptor may be hypoactive in depression. 4) Other Neurotransmitter Disturbances ­ Acetylcholine (ACh)- 8 -Page By Mohamed Abdelghani
  9. 9. Mood Disorders  Cholinergic neurons have interactive relationships with all three monoamine systems.  Abnormal levels of choline "a precursor to Ach" have been found at autopsy in the brains of some depressed patients, perhaps reflecting abnormalities in cell phospholipid composition.  Cholinergic agonist and antagonist drugs have differential clinical effects on depression and mania:  Agonists:  Can produce lethargy, anergia, and psychomotor retardation in healthy subjects  Can exacerbate symptoms in depression  Can reduce symptoms in mania.  Can induce changes in hypothalamic-pituitary adrenal (HPA) activity and sleep that mimic those associated with severe depression.  Some patients with mood disorders in remission, as well as their never-ill first-degree relatives, have a trait-like increase in sensitivity to cholinergic agonists. ­ γ-Aminobutyric acid (GABA)  It has an inhibitory effect on ascending monoamine pathways, particularly the mesocortical and mesolimbic systems.  Reductions of GABA were observed in plasma, CSF, and brain GABA levels in depression.  Animal studies have also found that chronic stress can reduce and eventually can deplete GABA levels.  By contrast, GABA receptors are upregulated by antidepressants, and some GABAergic medications have weak antidepressant effects. ­ Glutamate and Glycine  Glutamate and glycine are the major excitatory and inhibitory neurotransmitters in the CNS.  Glutamate and glycine bind to sites associated with the N-methyl-D- aspartate (NMDA) receptor, and an excess of glutamatergic stimulation can cause neurotoxic effects.  Importantly, a high concentration of NMDA receptors exists in the hippocampus. Glutamate, thus, may work in conjunction with hypercortisolemia to mediate the deleterious neurocognitive effects of severe recurrent depression.  Emerging evidence suggests that drugs that antagonize NMDA receptors have antidepressant effects.- 9 -Page By Mohamed Abdelghani
  10. 10. Mood Disorders b) Second Messengers and Intracellular Cascades  The binding of a neurotransmitter to the postsynaptic receptor triggers a cascade of membrane-bound and intracellular processes mediated by second messenger systems.  Receptors on cell membranes interact with the intracellular environment via guanine nucleotide-binding proteins (G proteins).  The G proteins, in turn, connect to various intracellular enzymes (e.g., adenylate cyclase, phospholipase C, and phosphodiesterase) that regulate utilization of energy and formation of second messengers, such as cyclic nucleotide (e.g., cAMP and cGMP , as well as phosphatidylinositols (e.g., inositol triphosphate and diacylglycerol) and calcium-calmodulin.  Second messengers regulate the function of neuronal membrane ion channels.  Increasing evidence also indicates that mood-stabilizing drugs act on G proteins or other second messengers. c) Alterations of Hormonal Regulation  Lasting alterations in neuroendocrine and behavioral responses can result from severe early stress.  Activity of the gene coding for the neurokinin brain-derived neurotrophic growth factor (BDNF) , as well as the process of neurogenesis are decreased after chronic stress.  Protracted stress thus can induce functional changes in neurons and, eventually, cell death.  Recent studies in depressed humans indicate that a history of early trauma is associated with increased HPA activity accompanied by structural changes (i.e., atrophy or decreased volume) in the cerebral cortex.  Elevated HPA activity is a hallmark of mammalian stress responses and one of the clearest links between depression and the biology of chronic stress.  Hypercortisolema in depression suggests one or more of the following central disturbances: ­ Decreased inhibitory serotonin tone. ­ Increased drive from norepinephrine, ACh, or CRH. ­ Decreased feedback inhibition from the hippocampus.  Elevated HPA activity in depression has been documented via: ­ Excretion of urinary-free cortisol (UFC). ­ 24-hour intravenous collections of plasma cortisol levels. ­ Salivary cortisol levels. ­ Tests of the integrity of feedback inhibition:- 10 -Page By Mohamed Abdelghani
  11. 11. Mood Disorders  Tested by administration of dexamethasone (Decadron) (0.5 to 2.0 mg), a potent synthetic glucocorticoid, "normally suppresses HPA axis activity for 24 hours".  Nonsuppression of cortisol secretion at 8:00 AM the following morning or subsequent escape from suppression at 4:00 PM or 11:00 PM is indicative of impaired feedback inhibition.  Hypersecretion of cortisol and dexamethasone nonsuppression are imperfectly correlated (approximately 60 percent concordance).  The sensitivity of the test can be improved by infusion of a test dose of CRH after dexamethasone suppression.  These tests of feedback inhibition are not used as a diagnostic test because adrenocortical hyperactivity is observed in mania, schizophrenia, dementia, and other psychiatric disorders. 1. Thyroid Axis Activity ­ Approximately 5 to 10% of people with depression have previously undetected thyroid dysfunction, as reflected by an elevated basal TSH level or an increased TSH response to a 500-mg infusion of the hypothalamic TRH. ­ Such abnormalities are often associated with elevated antithyroid antibody levels and, unless corrected with hormone replacement therapy, can compromise response to treatment. ­ An even larger subgroup of depressed patients (e.g., 20 to 30%) shows a blunted TSH response to TRH challenge. ­ To date, the major therapeutic implication of a blunted TSH response is evidence of an increased risk of relapse despite preventive antidepressant therapy. ­ Of note, unlike the dexamethasone suppression test (DST), blunted TSH response to TRH does not usually normalize with effective treatment. 2. Growth Hormone  Growth hormone (GH) is secreted from the anterior pituitary after stimulation by NE and Dopamine.  Secretion is inhibited by somatostatin, a hypothalamic neuropeptide, and CRH.  Decreased CSF somatostatin levels are reported in depression, and increased levels are observed in mania. 3. Prolactin- 11 -Page By Mohamed Abdelghani
  12. 12. Mood Disorders ­ Prolactin is released from the pituitary by serotonin stimulation and inhibited by DA. ­ Most studies have not found significant abnormalities of basal or circadian prolactin secretion in depression, although a blunted prolactin response to various serotonin agonists has been described. ­ This response is uncommon among premenopausal women, suggesting that estrogen has a moderating effect. d) Alterations of Sleep Neurophysiology  Depression is associated with a premature loss of deep (slow wave) sleep and an increase in nocturnal arousal.  The latter is reflected by four types of disturbance: (1) an increase in nocturnal awakenings. (2) a reduction in total sleep time. (3) increased phasic rapid eye movement (REM) sleep. (4) increased core body temperature.  The combination of increased REM drive and decreased slow wave sleep results in a significant reduction in the first period of non-REM (NREM) sleep, a phenomenon referred to as reduced REM latency.  Reduced REM latency and deficits of slow wave sleep typically persist after recovery of a depressive episode.  Blunted secretion of GH after sleep onset is associated with decreased slow wave sleep and shows similar state-independent or trait-like behavior.  The combination of reduced REM latency, increased REM density, and decreased sleep maintenance identifies approximately 40% of depressed outpatients and 80% of depressed inpatients.  False "negative" findings are commonly seen in younger, hypersomnolent patients, who may actually experience an increase in slow wave sleep during episodes of depression.  Approximately 10% of healthy individuals have abnormal sleep profiles, and, as with dexamethasone nonsuppression, false "positive" cases are not uncommonly seen in other psychiatric disorders.  Patients manifesting a characteristically abnormal sleep profile are less responsive to psychotherapy and have a greater risk of relapse or recurrence and may benefit preferentially from pharmacotherapy.- 12 -Page By Mohamed Abdelghani
  13. 13. Mood Disorders e) Immunological Disturbance ­ Depressive disorders are associated with several immunological abnormalities, including decreased lymphocyte proliferation in response to mitogens and other forms of impaired cellular immunity. ­ These lymphocytes produce neuromodulators, such as CRF, and cytokines "interleukins". ­ There may be an association with clinical severity, hypercortisolism, and immune dysfunction, and the cytokine interleukin-1 may induce gene activity for glucocorticoid synthesis. f) Structural and Functional Brain Imaging 1)CT and MRI scans  Have permitted sensitive, noninvasive methods to assess the living brain.  The most consistent abnormality in the depressive disorders is: ­ Abnormal hyperintensities in subcortical regions, such as periventricular regions, the basal ganglia, and the thalamus. These hyperintensities reflect the deleterious neurodegenerative effects of recurrent affective episodes. ­ Ventricular enlargement, cortical atrophy, and sulcal widening also are reported. ­ Some depressed patients also may have reduced hippocampal or caudate nucleus volumes, or both, suggesting more focal defects in relevant neurobehavioral systems.  Diffuse and focal areas of atrophy are associated with increased illness severity, bipolarity, and increased cortisol levels. 2)PET  In depression shows decreased anterior brain metabolism "more on the left side".  From a different point, depression may be associated with a relative increase in nondominant hemispheric activity.  Furthermore, a reversal of hypofrontality occurs after shifts from depression into hypomania, such that greater left hemisphere reductions are seen in depression compared with greater right hemisphere reductions in mania.  Other studies observed more specific reductions of reduced cerebral blood flow or metabolism, or both, in the dopaminergically innervated tracts of the mesocortical and mesolimbic systems in depression.- 13 -Page By Mohamed Abdelghani
  14. 14. Mood Disorders  Again, evidence suggests that antidepressants at least partially normalize these changes.  Also, increased glucose metabolism was observed in several limbic regions, particularly among patients with relatively severe recurrent depression and a family history of mood disorder.  During episodes of depression, increased glucose metabolism is correlated with intrusive ruminations. g) Neuroanatomical Considerations Modern affective neuroscience focuses on the importance of four brain regions in the regulation of normal emotions: 1. Prefrontal cortex (PFC). 2. Anterior cingulate. 3. Hippocampus. 4. Amygdala. 1) The PFC o Viewed as the structure that holds representations of goals and appropriate responses to obtain these goals. o Such activities are particularly important when multiple, conflicting behavioral responses are possible or when it is necessary to override affective arousal. o Evidence indicates some hemispherical specialization in PFC function: a) Activation of the left PFC is more involved in goal-directed or appetitive behaviors, b) Whereas, the right PFC is implicated in avoidance behaviors and inhibition of appetitive pursuits. c) Subregions in the PFC appear to localize representations of behaviors related to reward and punishment. 2) The anterior cingulate cortex (ACC)  Serve as the point of integration of attentional and emotional inputs.  Two subdivisions have been identified: 1. An affective subdivision in the rostral and ventral regions of the ACC. 2. A cognitive subdivision involving the dorsal ACC.- 14 -Page By Mohamed Abdelghani
  15. 15. Mood Disorders  The former subdivision shares extensive connections with other limbic regions, and the latter interacts more with the PFC and other cortical regions.  Activation of the ACC facilitates control of emotional arousal. 3) The hippocampus ­ Clearly involved in various forms of learning and memory, including fear conditioning, as well as inhibitory regulation of the HPA axis activity. ­ Emotional or contextual learning appears to involve a direct connection between the hippocampus and the amygdala. 4) The amygdala  A crucial way station for processing novel stimuli of emotional significance and coordinating cortical responses.  Located just above the hippocampi bilaterally, the amygdala has long been viewed as the heart of the limbic system.ii. Genetic Factors  Numerous family, adoption, and twin studies have long documented the heritability of mood disorders.  Recently, the primary focus of genetic studies is to identify specific susceptibility genes using molecular genetic methods. A. Family Studies:  If one parent has a mood disorder, a child will have a risk of between 10 and 25% for mood disorder.  If both parents are affected, this risk roughly doubles.  The more members of the family affected, the greater the risk is to a child.  The risk is greater if the affected family members are first-degree relatives.  A family history of bipolar disorder conveys a greater risk for mood disorders and, specifically, a much greater risk for bipolar disorder.  Unipolar disorder is typically the most common form of mood disorder in families of bipolar probands.  This familial overlap suggests some degree of common genetic underpinnings ‫ أﺳﺎس ﻣﺸﺘﺮك‬between these two forms of mood disorder.  The presence of more severe illness in the family also conveys a greater risk.- 15 -Page By Mohamed Abdelghani
  16. 16. Mood Disorders B. Adoption Studies:  Adoption studies provide an alternative approach to separating genetic and environmental factors in familial transmission.  One large study found a threefold increase in the rate of bipolar disorder and a twofold increase in unipolar disorder in the biological relatives of bipolar probands.  Similarly, in a Danish sample, a threefold increase in the rate of unipolar disorder and a sixfold increase in the rate of completed suicide in the biological relatives of affectively ill probands were reported.  However, other studies have found no difference in the rates of mood disorders. C. Twin Studies:  Twin studies provide the most powerful approach to separating genetic from environmental factors (nature from nurture).  The twin data provide compelling evidence that genes explain only 50 to 70% of the etiology of mood disorders, while environment or other nonheritable factors explain the remainder.  These studies find a concordance rate for mood disorder "unipolar and bipolar" in the monozygotic (MZ) twins of 70 to 90% compared with the same-sex dizygotic (DZ) twins of 16 to 35%. D. Linkage Studies: (Table 15.1-3). o DNA markers are segments of DNA of known chromosomal location, which are highly variable among individuals. o They are used to track the segregation of specific chromosomal regions within families affected with a disorder. o When a marker is identified with disease in families, the disease is said to be genetically linked. o Chromosomes 18q and 22q are the two regions with strongest evidence for linkage to bipolar disorder. o Several linkage studies found evidence for the involvement of specific genes in clinical subtypes: ­ For example, the linkage evidence on 18q has been shown to be derived largely from bipolar II-bipolar II sibling pairs and from families in which the probands had panic symptoms. ­ Studies of unipolar depression have found strong evidence of linkage to the locus for cAMP Response Element-Binding Protein (CREB1) on chromosome 2. Eighteen other genomic regions were found to be linked; some of these displayed interactions with the CREB1 locus.- 16 -Page By Mohamed Abdelghani
  17. 17. Mood Disorders o Another study has reported evidence for a gene-environment interaction in the development of major depression: ­ Subjects who underwent adverse life events were at an increased risk for depression. ­ However, of such subjects, those with a variant in the serotonin transporter gene showed the greatest increase in risk. Table 15.1-3: Selected Chromosomal Regions with Evidence of Linkage to Bipolar Disorder:  Data suggest the presence of as many as four different loci on this one chromosome. Chromosome  Studies found linkage to 18q to preferentially occur in families in 18 which affective illness was transmitted through the mother, suggesting a possible parent-of-origin effect. o Regions showed linkage or association to both schizophrenia and Chromosome bipolar disorder. 21q  The breakpoint cluster region (BCR) gene is located on chromosome 22q11. Chromosome  The BCR gene encodes an activating protein, which plays 22q important roles in neuron growth and axonal guidance.iii. Psychosocial Factors A. Life Events and Environmental Stress:  Stressful life events more often precede first, rather than subsequent, episodes of mood disorders.  This is reported for both patients with major depressive disorder and bipolar I disorder.  This is explained by: ­ The stress accompanying the first episode results in long-lasting changes in the brains biology. ­ These changes may alter the functional states of various neurotransmitter and intraneuronal signaling systems, including the loss of neurons and an excessive reduction in synaptic contacts.- 17 -Page By Mohamed Abdelghani
  18. 18. Mood Disorders  As a result, a person has a high risk of undergoing subsequent episodes of a mood disorder, even without an external stressor.  In Depression: ­ Some clinicians believe that life events play the primary or principal role in depression. ­ Others suggest that life events have only a limited role in the onset and timing of depression. ­ The life event most often associated with development of depression is losing a parent before age 11. ­ The environmental stressor most often associated with the onset of an episode of depression is the loss of a spouse. ­ Another risk factor is unemployment; persons out of work are three times more likely to report symptoms of an episode of major depression than those who are employed. B. Personality Factors: o No single personality type uniquely predisposes a person to depression. o All humans can become depressed under appropriate circumstances. o Persons with certain personality disorders "OCD, histrionic, and borderline" may be at greater risk for depression than persons with antisocial or paranoid personality disorder. o The latter can use projection and other externalizing defense mechanisms to protect themselves from their inner rage. o No evidence indicates that any particular personality disorder is associated with later development of bipolar I disorder; however, patients with dysthymic disorder and cyclothymic disorder are at risk of later developing major depression or bipolar I disorder. o Recent stressful events are the most powerful predictors of the onset of a depressive episode. o The clinician is always interested in the meaning of the stressor: ­ The stressors experienced as reflecting negatively on his or her self-esteem are more likely to produce depression. ­ Howover, what may seem to be a relatively mild stressor to outsiders may be devastating to the patient because of particular idiosyncratic meanings attached to the event. C. Psychodynamic Factors in Depression: 1) The classic view of depression "Defined by Sigmund Freud and expanded by Karl Abraham":- 18 -Page By Mohamed Abdelghani
  19. 19. Mood Disorders  That theory involves four key points: a) Disturbances in the infant-mother relationship during the oral phase (the first 10 to 18 months of life) predispose to subsequent vulnerability to depression. b) Depression can be linked to real or imagined object loss. c) Introjection of the departed "lost" objects is "Defense mechanism". d) Because the lost object is regarded with a mixture of love and hate, feelings of anger are directed inward at the self. 2) Melanie Klein: o Depression involves the expression of aggression toward loved ones. 3) Edward Bibring:  Depression sets in when a person becomes aware of the discrepancy between extraordinarily high ideals and the inability to meet those goals. 4) Edith Jacobson:  Depression is similar to a powerless, helpless child victimized by a tormenting parent. 5) Silvano Arieti: o Depression sets in when patients realize that the person or ideal "the dominant other" for which they have been living is never going to respond in a manner that will meet their expectations. 6) Heinz Kohut:  His self-psychological theory of depression assumes that the developing self has specific needs that must be met by parents to give the child a positive sense of self-esteem and self-cohesion.  When others do not meet these needs, there is a massive loss of self- esteem that presents as depression. 7) John Bowlby:  Damaged early attachments and traumatic separation in childhood predispose to depression.  Adult losses are said to revive the traumatic childhood loss and so precipitate adult depressive episodes.- 19 -Page By Mohamed Abdelghani
  20. 20. Mood Disorders D. Psychodynamic Factors in Mania:  Most theories of mania view manic episodes as a defense against underlying depression: 1) Abraham: ­ Manic episodes may reflect an inability to tolerate a developmental tragedy, such as the loss of a parent. ­ Also, the manic state may result from a tyrannical superego, which produces intolerable self-criticism that is then replaced by euphoric self- satisfaction. 2) Bertram Lewin: ­ The manic patients ego is overwhelmed by pleasurable impulses, such as sex, or by feared impulses, such as aggression. 3) Melanie Klein: ­ Mania is a defensive reaction to depression, using manic defenses such as omnipotence, in which the person develops delusions of grandeur. E. Other Formulations of Depression: 1. Cognitive Theory: (Table 15.1-4). ­ According to the theory, depression results from specific cognitive distortions present in persons susceptible to depression. ­ Those distortions are referred as depressogenic schemata. ­ Aaron Beck postulated a cognitive triad of depression that consists of : 1) Views about the self: "a negative self-precept". 2) About the environment: a tendency to experience the world as hostile and demanding. 3) About the future: "the expectation of suffering and failure". ­ Therapy consists of modifying these distortions. 2. Learned Helplessness: ­ The learned helplessness theory of depression connects depressive phenomena to the experience of uncontrollable events. ­ According to the learned helplessness theory, when dogs were exposed to electrical shocks from which they could not escape, the shocked dogs then- 20 -Page By Mohamed Abdelghani
  21. 21. Mood Disorders learned that outcomes were independent of responses, so they had both cognitive motivational deficit (i.e., they would not attempt to escape the shock) and emotional deficit (decreased reactivity to the shock). ­ In human depression, internal causal explanations produce a loss of self-esteem after adverse external events. ­ Behaviorists claimed that improvement of depression is contingent on the patients learning a sense of control and mastery of the environment. Table 15.1-4 Elements of Cognitive Theory: Element Definition Cognitive triad Beliefs about oneself, the world, the future Ways of organizing and interpreting Schemas experiences Cognitive distortions:  Arbitrary inference Drawing a specific conclusion without sufficient evidence  Specific abstraction Focus on a single detail while ignoring other, more important aspects of an experience  Overgeneralization Forming conclusions based on too little and too narrow experience  Magnification and Over- or undervaluing the significance of a minimization particular event  Personalization Tendency to self-reference external events without basis  Absolutist, dichotomous Tendency to place experience into all-or-none thinking categories- 21 -Page By Mohamed Abdelghani
  22. 22. Mood Disorders Diagnosis In addition to the diagnostic criteria for major depressive disorder and bipolar disorders,DSM-IV-TR includes specific criteria for mood episodes and criteria, such as severity toqualify the most recent episode.i. Major Depressive Disorder Table 15.1-5 DSM-IV-TR Criteria for Major Depressive Episode: A. Five (or more) of the following symptoms have been present during the same 2- week period and represent a change from previous functioning; at least one of the symptoms is either: (1) depressed mood or (2) loss of interest or pleasure. Note: Do not include symptoms that are clearly due to a general medical condition, or mood- incongruent delusions or hallucinations. 1. depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad or empty) or observation made by others (e.g., appears tearful). Note: In children and adolescents, can be irritable mood 2. markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by either subjective account or observation made by others) 3. significant weight loss when not dieting or weight gain (e.g., a change of more than 5% of body weight in a month), or decrease or increase in appetite nearly every day. Note: In children, consider failure to make expected weight gains. 4. insomnia or hypersomnia nearly every day 5. psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down) 6. fatigue or loss of energy nearly every day 7. feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely self-reproach or guilt about being sick) 8. diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others) 9. recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide B. The symptoms do not meet criteria for a mixed episode. C. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.- 22 -Page By Mohamed Abdelghani
  23. 23. Mood Disorders D. The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication) or a general medical condition (e.g., hypothyroidism). E. The symptoms are not better accounted for by bereavement, i.e., after the loss of a loved one, the symptoms persist for longer than 2 months or are characterized by marked functional impairment, morbid preoccupation with worthlessness, suicidal ideation, psychotic symptoms, or psychomotor retardation. A. Major Depressive Disorder, Single Episode: (Table 15.1-12).  Differentiation between these patients and those with two or more episodes is justified because of the uncertain course of the former patients disorder.  Several studies reported that major depression covers a heterogeneous population of disorders.  One type of study assessed the stability of a diagnosis of major depression in a patient over time. The study found that 25 to 50% of the patients were later reclassified as having a different psychiatric condition or a nonpsychiatric medical condition with psychiatric symptoms.  A second type of study evaluated first-degree relatives of affectively ill patients to determine the presence and types of psychiatric diagnoses for these relatives over time.  Both types of studies found that depressed patients with more depressive symptoms are more likely to have stable diagnoses over time and are more likely to have affectively ill relatives than are depressed patients with fewer depressive symptoms.  Also, patients with bipolar I disorder and those with bipolar II disorder (recurrent major depressive episodes with hypomania) are likely to have stable diagnoses over time.Table 15.1-12 DSM-IV-TR Diagnostic Criteria for Major Depressive Disorder, Single Episode: A. Presence of a single major depressive episode. B. The major depressive episode is not better accounted for by schizoaffective disorder and is not superimposed on schizophrenia, schizophreniform disorder, delusional disorder, or psychotic disorder not otherwise specified. C. There has never been a manic episode, a mixed episode, or a hypomanic episode. Note: This exclusion does not apply if all of the manic-like, mixed-like, or hypomanic-like episodes are substance or treatment induced or are due to the direct physiological effects of a general medical condition.- 23 -Page By Mohamed Abdelghani
  24. 24. Mood Disorders If the full criteria are currently met for a major depressive episode, specify its current clinical status and/or features:  Mild, moderate, severe without psychotic features/severe with psychotic features  Chronic  With catatonic features  With melancholic features  With atypical features  With postpartum onset If the full criteria are not currently met for a major depressive episode, specify the current clinical status of the major depressive disorder or features of the most recent episode: o In partial remission, in full remission o Chronic o With catatonic features o With melancholic features o With atypical features o With postpartum onset B. Major Depressive Disorder, Recurrent: (Table 15.1-13).  Patients who are experiencing at least a second episode of depression are classified in DSM-IV-TR as having major depressive disorder, recurrent.  The essential problem with diagnosing recurrent episodes of major depressive disorder is choosing the criteria to designate the resolution of each period.  Two variables are the degree of resolution of the symptoms and the length of the resolution.  DSM-IV-TR requires that distinct episodes of depression be separated by at least 2 months during which a patient has no significant symptoms of depression. Table 15.1-13 DSM-IV-TR Diagnostic Criteria for Major Depressive Disorder, Recurrent: A. Presence of two or more major depressive episodes. Note: To be considered separate episodes, there must be an interval of at least 2 consecutive months in which criteria are not met for a major depressive episode. B. The major depressive episodes are not better accounted for by schizoaffective disorder and are not superimposed on schizophrenia, schizophreniform disorder, delusional disorder, or psychotic disorder not otherwise specified. C. There has never been a manic episode, a mixed episode, or a hypomanic episode.- 24 -Page By Mohamed Abdelghani
  25. 25. Mood Disorders Note: This exclusion does not apply if all of the manic-like, mixed-like, or hypomanic-like episodes are substance or treatment induced or are due to the direct physiological effects of a general medical condition. If the full criteria are currently met for a major depressive episode, specify its current clinical status and/or features:  Mild, moderate, severe without psychotic features/severe with psychotic features  Chronic  With catatonic features  With melancholic features  With atypical features  With postpartum onset If the full criteria are not currently met for a major depressive episode, specify the current clinical status of the major depressive disorder or features of the most recent episode: o In partial remission, in full remission o Chronic o With catatonic features o With melancholic features o With atypical features o With postpartum onset Specify if: ­ Longitudinal course specifiers (with and without interepisode recovery) ­ With seasonal patternii. Bipolar I Disorder  The DSM-IV-TR criteria for a manic episode requires the presence of a distinct period of abnormal mood lasting at least 1 week and includes separate bipolar I disorder diagnoses for a single manic episode and a recurrent episode, based on the symptoms of the most recent episode as described below.  The designation bipolar I disorder is synonymous with what was formerly known as "bipolar disorder" a syndrome in which a complete set of mania symptoms occurs during the course of the disorder.  The diagnostic criteria for bipolar II disorder is characterized by depressive episodes and hypomanic episodes during the course of the disorder, but the episodes of manic- like symptoms do not quite meet the diagnostic criteria for a full manic syndrome.  Manic episodes precipitated by antidepressant treatment (e.g., pharmacotherapy, electroconvulsive therapy [ECT]) do not indicate bipolar I disorder. A. Bipolar I Disorder, Single Manic Episode: (Table 15.1-14).- 25 -Page By Mohamed Abdelghani
  26. 26. Mood Disorders ­ According to DSM-IV-TR, patients must be experiencing their first manic episode to meet the diagnostic criteria for bipolar I disorder, single manic episode. ­ This requirement rests on the fact that patients who are having their first episode of bipolar I disorder depression cannot be distinguished from patients with major depressive disorder. Table 15.1-14 DSM-IV-TR Diagnostic Criteria for Bipolar I Disorder, Single Manic Episode: A. Presence of only one manic episode and no past major depressive episodes. Note: Recurrence is defined as either a change in polarity from depression or an interval of at least 2 months without manic symptoms. B. The manic episode is not better accounted for by schizoaffective disorder and is not superimposed on schizophrenia, schizophreniform disorder, delusional disorder, or psychotic disorder not otherwise specified. Specify if:  Mixed: if symptoms meet criteria for a mixed episode If the full criteria are currently met for a manic, mixed, or major depressive episode, specify its current clinical status and/or features:  Mild, moderate, severe without psychotic features/severe with psychotic features  With catatonic features  With postpartum onset If the full criteria are not currently met for a manic, mixed, or major depressive episode, specify the current clinical status of the bipolar I disorder or features of the most recent episode:  In partial remission, in full remission  With catatonic features  With postpartum onset B. Bipolar I Disorder, RecurrentManic episodes are considered distinct when they are separated by at least 2 monthswithout significant symptoms of mania or hypomania.DSM-IV-TR specifies diagnostic criteria for recurrent bipolar I disorder on the basis of thesymptoms of the most recent episode:  Bipolar I disorder, most recent episode manic (Table 15.1-15).  Bipolar I disorder, most recent episode hypomanic (Table 15.1-16).  Bipolar I disorder, most recent episode depressed (Table 15.1-17).  Bipolar I disorder, most recent episode mixed (Table 15.1-18).  Bipolar I disorder, most recent episode unspecified (Table 15.1-19).- 26 -Page By Mohamed Abdelghani
  27. 27. Mood Disorders Table 15.1-15 DSM-IV-TR Diagnostic Criteria for Bipolar I Disorder, Most Recent Episode Manic A. Currently (or most recently) in a manic episode. B. There has previously been at least one major depressive episode, manic episode, or mixed episode. C. The mood episodes in Criteria A and B are not better accounted for by schizoaffective disorder and are not superimposed on schizophrenia, schizophreniform disorder, delusional disorder, or psychotic disorder not otherwise specified. If the full criteria are currently met for a manic episode, specify its current clinical status and/or features:  Mild, moderate, severe without psychotic features/severe with psychotic features  With catatonic features  With postpartum onset If the full criteria are not currently met for a manic episode, specify the current clinical status of the bipolar I disorder and/or features of the most recent manic episode:  In partial remission, in full remission  With catatonic features  With postpartum onset Specify if:  Longitudinal course specifiers (with and without interepisode recovery)  With seasonal pattern (applies only to the pattern of major depressive episodes)  With rapid cycling Table 15.1-16 DSM-IV-TR Diagnostic Criteria for Bipolar I Disorder, Most Recent Episode Hypomanic: A. Currently (or most recently) in a hypomanic episode. B. There has previously been at least one manic episode or mixed episode. C. The mood symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. D. The mood episodes in Criteria A and B are not better accounted for by schizoaffective disorder and are not superimposed on schizophrenia, schizophreniform disorder, delusional disorder, or psychotic disorder not otherwise specified. Specify if:  Longitudinal course specifiers (with and without interepisode recovery)  With seasonal pattern (applies only to the pattern of major depressive episodes)  With rapid cycling- 27 -Page By Mohamed Abdelghani
  28. 28. Mood Disorders Table 15.1-17 DSM-IV-TR Diagnostic Criteria for Bipolar I Disorder, Most Recent Episode Depressed: A. Currently (or most recently) in a major depressive episode. B. There has previously been at least one manic episode or mixed episode. C. The mood episodes in Criteria A and B are not better accounted for by schizoaffective disorder and are not superimposed on schizophrenia, schizophreniform disorder, delusional disorder, or psychotic disorder not otherwise specified. If the full criteria are currently met for a major depressive episode, specify its current clinical status and/or features:  Mild, moderate, severe without psychotic features/severe with psychotic features  Chronic With catatonic features  With melancholic features  With atypical features  With postpartum onset If the full criteria are not currently met for a major depressive episode, specify the current clinical status of the bipolar I disorder and/or features of the most recent major depressive episode: o In partial remission, in full remission o Chronic o With catatonic features o With melancholic features o With atypical features o With postpartum onset Specify if:  Longitudinal course specifiers (with and without interepisode recovery)  With seasonal pattern (applies only to the pattern of major depressive episodes)  With rapid cycling Table 15.1-8 DSM-IV-TR Criteria for Mixed Episode: A. The criteria are met both for a manic episode and for a major depressive episode (except for duration) nearly every day during at least a 1-week period. B. The mood disturbance is sufficiently severe to cause marked impairment in occupational functioning or in usual social activities or relationships with others, or to necessitate hospitalization to prevent harm to self or others, or there are psychotic features. C. The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication, or other treatment) or a general medical condition- 28 -Page By Mohamed Abdelghani
  29. 29. Mood Disorders (e.g., hyperthyroidism). Note: Mixed-like episodes that are clearly caused by somatic antidepressant treatment (e.g., medication, electroconvulsive therapy, light therapy) should not count toward a diagnosis of bipolar I disorder. Table 15.1-18 DSM-IV-TR Diagnostic Criteria for Bipolar I Disorder, Most Recent Episode Mixed: A. Currently (or most recently) in a mixed episode. B. There has previously been at least one major depressive episode, manic episode, or mixed episode. C. The mood episodes in Criteria A and B are not better accounted for by schizoaffective disorder and are not superimposed on schizophrenia, schizophreniform disorder, delusional disorder, or psychotic disorder not otherwise specified. If the full criteria are currently met for a mixed episode, specify its current clinical status and/or features:  Mild, moderate, severe without psychotic features/severe with psychotic features  With catatonic features  With postpartum onset If the full criteria are not currently met for a mixed episode, specify the current clinical status of the bipolar I disorder and/or features of the most recent mixed episode: o In partial remission, in full remission o With catatonic features o With postpartum onset Specify if:  Longitudinal course specifiers (with and without interepisode recovery)  With seasonal pattern (applies only to the pattern of major depressive episodes)  With rapid cycling Table 15.1-19 DSM-IV-TR Diagnostic Criteria for Bipolar I Disorder, Most Recent Episode Unspecified: A. Criteria, except for duration, are currently (or most recently) met for a manic, a hypomanic, a mixed, or a major depressive episode. B. There has previously been at least one manic episode or mixed episode. C. The mood symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. D. The mood symptoms in Criteria A and B are not better accounted for by schizoaffective disorder and are not superimposed on schizophrenia,- 29 -Page By Mohamed Abdelghani
  30. 30. Mood Disorders schizophreniform disorder, delusional disorder, or psychotic disorder not otherwise specified. E. The mood symptoms in Criteria A and B are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication, or other treatment) or a general medical condition (e.g., hyperthyroidism). Specify if:  Longitudinal course specifiers (with and without interepisode recovery)  With seasonal pattern (applies only to the pattern of major depressive episodes)  With rapid cyclingiii. Bipolar II Disorder  The diagnostic criteria for bipolar II disorder specify the particular severity, frequency, and duration of the hypomanic symptoms.  The diagnostic criteria for a hypomanic episode (Table 15.1-7) are listed separately from the criteria for bipolar II disorder (Table 15.1-20).  The criteria have been established to decrease overdiagnosis of hypomanic episodes and the incorrect classification of patients with major depressive disorder as patients with bipolar II disorder.  Clinically, psychiatrists may find it difficult to distinguish euthymia from hypomania in a patient who is chronically depressed for many months or years.  As with bipolar I disorder, antidepressant-induced hypomanic episodes are not diagnostic of bipolar II disorder. Table 15.1-7 DSM-IV-TR Criteria for Hypomanic Episode: A. A distinct period of persistently elevated, expansive, or irritable mood, lasting throughout at least 4 days, that is clearly different from the usual nondepressed mood. B. During the period of mood disturbance, three (or more) of the following symptoms have persisted (four if the mood is only irritable) and have been present to a significant degree: 1. inflated self-esteem or grandiosity 2. decreased need for sleep (e.g., feels rested after only 3 hours of sleep) 3. more talkative than usual or pressure to keep talking 4. flight of ideas or subjective experience that thoughts are racing 5. distractibility (i.e., attention too easily drawn to unimportant or irrelevant external stimuli) 6. increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation- 30 -Page By Mohamed Abdelghani
  31. 31. Mood Disorders 7. excessive involvement in pleasurable activities that have a high potential for painful consequences (e.g., the person engages in unrestrained buying sprees, sexual indiscretions, or foolish business investments) C. The episode is associated with an unequivocal change in functioning that is uncharacteristic of the person when not symptomatic. D. The disturbance in mood and the change in functioning are observable by others. E. The episode is not severe enough to cause marked impairment in social or occupational functioning, or to necessitate hospitalization, and there are no psychotic features. F. The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication, or other treatment) or a general medical condition (e.g., hyperthyroidism). Note: Hypomanic-like episodes that are clearly caused by somatic antidepressant treatment (e.g., medication, electroconvulsive therapy, light therapy) should not count toward a diagnosis of bipolar II disorder. Table 15.1-20 DSM-IV-TR Diagnostic Criteria for Bipolar II Disorder: A. Presence (or history) of one or more major depressive episodes. B. Presence (or history) of at least one hypomanic episode. C. There has never been a manic episode or a mixed episode. D. The mood symptoms in Criteria A and B are not better accounted for by schizoaffective disorder and are not superimposed on schizophrenia, schizophreniform disorder, delusional disorder, or psychotic disorder not otherwise specified. E. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. Specify current or most recent episode:  Hypomanic: if currently (or most recently) in a hypomanic episode  Depressed: if currently (or most recently) in a major depressive episode If the full criteria are currently met for a major depressive episode, specify its current clinical status and/or features: o Mild, moderate, severe without psychotic features/severe with psychotic features. Note: Fifth-digit codes cannot be used here because the code for bipolar II disorder already uses the fifth digit. o Chronic o With catatonic features o With melancholic features o With atypical features o With postpartum onset If the full criteria are not currently met for a hypomanic or major depressive episode, specify the clinical status of the bipolar II disorder and/or features of the most recent- 31 -Page By Mohamed Abdelghani
  32. 32. Mood Disorders major depressive episode (only if it is the most recent type of mood episode):  In partial remission, in full remission. Note: Fifth-digit codes cannot be used here because the code for bipolar II disorder already uses the fifth digit.  Chronic  With catatonic features  With melancholic features  With atypical features  With postpartum onset Specify if:  Longitudinal course specifiers (with and without interepisode recovery)  With seasonal pattern (applies only to the pattern of major depressive episodes)  With rapid cyclingN.B.1: Specifiers Describing Most Recent Episode:  In addition to the severity, psychotic, and remission specifiers (Tables 15.1-7,15.1- 8,15.1-9,15.1-10,15.1-11), DSM-IV-TR defines additional symptom features that can be used to describe patients with various mood disorders.  Two of the features (melancholic and atypical) are limited to describing depressive episodes.  Two others (catatonic features and with postpartum onset) can be applied to depressive and manic episodes.  These are described below:  With Psychotic Features: (Table 15.1-7).  The presence of psychotic features in major depressive disorder reflects severe disease and a poor prognosis.  A review comparing psychotic with nonpsychotic major depressive disorder indicates that the two conditions may be distinct in their pathogenesis:  One difference is that bipolar I disorder is more common in the families of probands with psychotic depression than in the families of probands with nonpsychotic depression.  The psychotic symptoms are often categorized as either mood congruent e.g. "I deserve to be punished because I am so bad", or mood incongruent, not in harmony with the mood disorder.  Patients with mood disorder with mood-congruent psychoses have a psychotic type of mood disorder; however, patients with mood disorder with mood-incongruent psychotic symptoms may have schizoaffective disorder or schizophrenia.- 32 -Page By Mohamed Abdelghani
  33. 33. Mood Disorders  The following factors are associated with a poor prognosis for patients with mood disorders:  Long duration of episodes.  Temporal dissociation ‫ اﻻﻧﻔﺼ ﺎل اﻟﻤﺆﻗ ﺖ‬between the mood disorder and the psychotic symptoms.  A poor premorbid history of social adjustment.  The presence of psychotic features also has significant treatment implications:  The patients typically require antipsychotic drugs in addition to antidepressants or mood stabilizers and may need ECT to obtain clinical improvement.  With Melancholic Features: (Table 15.1-21). ­ Melancholia is one of the oldest terms in psychiatry "Hippocrates in the 4th century" to describe the dark mood of depression. ­ It is still used to refer to a depression characterized by:  Severe anhedonia.  Early morning awakening.  Weight loss.  Profound feelings of guilt (often over trivial events). ­ It is not uncommon for patients who are melancholic to have suicidal ideation. ­ Melancholia is associated with changes in the autonomic nervous system and in endocrine functions. For that reason, melancholia is sometimes referred to as "endogenous depression" or depression that arises in the absence of external life stressors. ­ The DSM-IV-TR melancholic features can be applied to major depressive episodes in major depressive disorder, bipolar I disorder, or bipolar II disorder. Table 15.1-21 DSM-IV-TR Criteria for Melancholic Features Specifier: Specify if: With melancholic features (can be applied to the current or most recent major depressive episode in major depressive disorder and to a major depressive episode in bipolar I or bipolar II disorder only if it is the most recent type of mood episode) A. Either of the following, occurring during the most severe period of the current episode: 1. loss of pleasure in all, or almost all, activities- 33 -Page By Mohamed Abdelghani
  34. 34. Mood Disorders 2. lack of reactivity to usually pleasurable stimuli (does not feel much better, even temporarily, when something good happens) B. Three (or more) of the following: 1. distinct quality of depressed mood (i.e., the depressed mood is experienced as distinctly different from the kind of feeling experienced after the death of a loved one) 2. depression regularly worse in the morning 3. early morning awakening (at least 2 hours before usual time of awakening) 4. marked psychomotor retardation or agitation 5. significant anorexia or weight loss 6. excessive or inappropriate guilt  With Atypical Features: (Table 15.1-22).  The patients with atypical features have specific characteristics as overeating and oversleeping.  These symptoms are sometimes referred to as reversed vegetative symptoms, and the symptom pattern is sometimes called hysteroid dysphoria.  When patients with atypical depression are compared with patients with typical depression features, the patients with atypical features are found to have: 1. A younger age of onset. 2. More severe psychomotor slowing. 3. More frequent coexisting diagnoses of panic disorder. 4. Substance abuse or dependence. 5. Somatization disorder.  The high incidence and severity of anxiety symptoms in patients with atypical features are sometimes correlated with the likelihood of being misclassified as having an anxiety disorder rather than a mood disorder.  Patients with atypical features may also have a long-term course, a diagnosis of bipolar I disorder, or a seasonal pattern to their disorder.  The DSM-IV-TR atypical features can be applied to the most recent major depressive episode in major depressive disorder, bipolar I disorder, bipolar II disorder, or dysthymic disorder. Table 15.1-22 DSM-IV-TR Criteria for Atypical Features Specifier: Specify if: With atypical features (can be applied when these features predominate during the most recent 2 weeks of a current major depressive episode in major depressive disorder or in bipolar I or bipolar II disorder when a current major depressive episode is the most recent type of mood episode, or when these features predominate during the most- 34 -Page By Mohamed Abdelghani
  35. 35. Mood Disorders recent 2 years of dysthymic disorder; if the major depressive episode is not current, it applies if the feature predominates during any 2-week period): A. Mood reactivity (i.e., mood brightens in response to actual or potential positive events) B. Two (or more) of the following features: 1. significant weight gain or increase in appetite 2. hypersomnia 3. leaden paralysis (i.e., heavy, leaden feelings in arms or legs) 4. long-standing pattern of interpersonal rejection sensitivity (not limited to episodes of mood disturbance) that results in significant social or occupational impairment C. Criteria are not met for with melancholic features or with catatonic features during the same episode.  With Catatonic Features: (Table 15.1-23).  As a symptom, catatonia can be present in several mental disorders, most commonly, schizophrenia and the mood disorders.  The presence of catatonic features in patients with mood disorders may have prognostic and treatment significance.  The hallmark symptoms of catatonia "stuporousness, blunted affect, extreme withdrawal, negativism, and marked psychomotor retardation" can be seen in both catatonic and noncatatonic schizophrenia, major depressive disorder (often with psychotic features), and medical and neurological disorders.  Clinicians often do not associate catatonic symptoms with bipolar I disorder because of the marked contrast between the symptoms of stuporous catatonia and the classic symptoms of mania.  Because catatonic symptoms are a behavioral syndrome appearing in several medical and psychiatric conditions, catatonic symptoms do not imply a single diagnosis. Table 15.1-23 DSM-IV-TR Criteria for Catatonic Features Specifier: Specify if: With catatonic features (can be applied to the current or most recent major depressive episode, manic episode, or mixed episode in major depressive disorder, bipolar I disorder, or bipolar II disorder) The clinical picture is dominated by at least two of the following: 1. motoric immobility as evidenced by catalepsy (including waxy flexibility) or stupor- 35 -Page By Mohamed Abdelghani
  36. 36. Mood Disorders 2. excessive motor activity (that is apparently purposeless and not influenced by external stimuli) 3. extreme negativism (an apparently motiveless resistance to all instructions or maintenance of a rigid posture against attempts to be moved) or mutism 4. peculiarities of voluntary movement as evidenced by posturing (voluntary assumption of inappropriate or bizarre postures), stereotyped movements, prominent mannerisms, or prominent grimacing 5. echolalia or echopraxia  Postpartum Onset: (Table 15.1-24). ­ DSM-IV-TR specifies a postpartum mood disturbance if the onset of symptoms is within 4 weeks postpartum. ­ Postpartum mental disorders commonly include psychotic symptoms. Table 15.1-24 DSM-IV-TR Criteria for Postpartum Onset Specifier: Specify if: With postpartum onset (can be applied to the current or most recent major depressive, manic, or mixed episode in major depressive disorder, bipolar I disorder, or bipolar II disorder; or to brief psychotic disorder)  Onset of episode within 4 weeks postpartum  Chronic: (Table 15.1-25). o DSM-IV-TR specifies chronic to describe major depressive episodes that occur as a part of major depressive disorder, bipolar I disorder, and bipolar II disorder. Table 15.1-25 DSM-IV-TR Criteria for Chronic Specifier Specify if: Chronic (can be applied to the current or most recent major depressive episode in major depressive disorder and to a major depressive episode in bipolar I or II disorder only if it is the most recent type of mood episode)  Full criteria for a major depressive episode have been met continuously for at least the past 2 years.  Severity/Psychotic/ Remission Specifiers: Table 15.1-9 DSM-IV-TR Criteria for Severity/Psychotic/ Remission Specifiers for Current (or Most Recent) Major Depressive Episode: Note: Code in fifth digit. Mild, moderate, severe without psychotic features, and severe with psychotic features- 36 -Page By Mohamed Abdelghani
  37. 37. Mood Disorders can be applied only if the criteria are currently met for a major depressive episode. In partial remission and in full remission can be applied to the most recent major depressive episode in major depressive disorder and to a major depressive episode in bipolar I or II disorder only if it is the most recent type of mood episode.  Mild: Few, if any, symptoms in excess of those required to make the diagnosis and symptoms result in only minor impairment in occupational functioning or in usual social activities or relationships with others.  Moderate: Symptoms or functional impairment between "mild" and "severe".  Severe without psychotic features: Several symptoms in excess of those required to make the diagnosis, and symptoms markedly interfere with occupational functioning or with usual social activities or relationships with others.  Severe with psychotic features: Delusions or hallucinations. If possible, specify whether the psychotic features are mood-congruent or mood-incongruent: o Mood-congruent psychotic features: Delusions or hallucinations whose content is entirely consistent with the typical depressive themes of personal inadequacy, guilt, disease, death, nihilism, or deserved punishment. o Mood-incongruent psychotic features: Delusions or hallucinations whose content does not involve typical depressive themes of personal inadequacy, guilt, disease, death, nihilism, or deserved punishment. Included are such symptoms as persecutory delusions (not directly related to depressive themes), thought insertion, thought broadcasting, and delusions of control.  In partial remission: Symptoms of a major depressive episode are present but full criteria are not met, or there is a period without any significant symptoms of a major depressive episode lasting less than 2 months following the end of the major depressive episode. (If the major depressive episode was superimposed on dysthymic disorder, the diagnosis of dysthymic disorder alone is given once the full criteria for a major depressive episode are no longer met.)  In full remission: During the past 2 months, no significant signs or symptoms of the disturbance were present.  Unspecified. Table 15.1-10 DSM-IV-TR Criteria for Severity/Psychotic/ Remission Specifiers for Current (or Most Recent) Manic Episode Note: Code in fifth digit. Mild, moderate, severe without psychotic features, and severe with psychotic features can be applied only if the criteria are currently met for a manic episode. In partial remission and in full remission can be applied to a manic episode in bipolar I disorder only if it is the most recent type of mood episode.  Mild: Minimum symptom criteria are met for a manic episode.  Moderate: Extreme increase in activity or impairment in judgment.  Severe without psychotic features: Almost continual supervision required to prevent physical harm to self or others.  Severe with psychotic features: Delusions or hallucinations. If possible, specify whether the psychotic features are mood-congruent or mood-incongruent:- 37 -Page By Mohamed Abdelghani
  38. 38. Mood Disorders o Mood-congruent psychotic features: Delusions or hallucinations whose content is entirely consistent with the typical manic themes of inflated worth, power, knowledge, identity, or special relationship to a deity or famous person. o Mood-incongruent psychotic features: Delusions or hallucinations whose content does not involve typical manic themes of inflated worth, power, knowledge, identity, or special relationship to a deity or famous person. Included are such symptoms as persecutory delusions (not directly related to grandiose ideas or themes), thought insertion, and delusions of being controlled.  In partial remission: Symptoms of a manic episode are present but full criteria are not met, or there is a period without any significant symptoms of a manic episode lasting less than 2 months following the end of the manic episode.  In full remission: During the past 2 months no significant signs or symptoms of the disturbance were present.  Unspecified. Table 15.1-11 DSM-IV-TR Criteria for Severity/Psychotic/ Remission Specifiers for Current (or Most Recent) Mixed Episode: Note: Code in fifth digit. Mild, moderate, severe without psychotic features, and severe with psychotic features can be applied only if the criteria are currently met for a mixed episode. In partial remission and in full remission can be applied to a mixed episode in bipolar I disorder only if it is the most recent type of mood episode.  Mild: No more than minimum symptom criteria are met for both a manic episode and a major depressive episode.  Moderate: Symptoms or functional impairment between "mild"and "severe".  Severe without psychotic features: Almost continual supervision required to prevent physical harm to self or others.  Severe with psychotic features: Delusions or hallucinations. If possible, specify whether the psychotic features are mood-congruent or mood-incongruent: o Mood-congruent psychotic features: Delusions or hallucinations whose content is entirely consistent with the typical manic or depressive themes. o Mood-incongruent psychotic features: Delusions or hallucinations whose content does not involve typical manic or depressive themes. Included are such symptoms as persecutory delusions (not directly related to grandiose or depressive themes), thought insertion, and delusions of being controlled.  In partial remission: Symptoms of a mixed episode are present but full criteria are not met, or there is a period without any significant symptoms of a mixed episode lasting less than 2 months following the end of the mixed episode.  In full remission: During the past 2 months, no significant signs or symptoms of the disturbance were present.  Unspecified.- 38 -Page By Mohamed Abdelghani
  39. 39. Mood DisordersN.B.2: Describing Course of Recurrent Episodes: o The DSM-IV-TR includes criteria for three distinct course specifiers for mood disorders: 1. With rapid cycling: restricted to bipolar I disorder and bipolar II disorder. 2. With seasonal pattern. 3. With or without full interepisode recovery. o Both "2&3" can be applied to bipolar I disorder, bipolar II disorder, and major depressive disorder, recurrent.N.B.: The course specifier with postpartum onset can be applied to major depressive ormanic episodes in bipolar I disorder, bipolar II disorder, major depressive disorder, andbrief psychotic disorder.  Rapid Cycling: (Table 15.1-26). ­ Patients with rapid cycling bipolar I disorder are likely to be female and to have had depressive and hypomanic episodes. ­ No data indicate that rapid cycling has a familial pattern of inheritance and, thus, an external factor such as stress or drug treatment may be involved in the pathogenesis of rapid cycling. ­ The DSM-IV-TR criteria specify that the patient must have at least four episodes within a 12-month period. Table 15.1-26 DSM-IV-TR Criteria for Rapid-Cycling Specifier: Specify if: With rapid cycling (can be applied to bipolar I disorder or bipolar II disorder) At least four episodes of a mood disturbance in the previous 12 months that meet criteria for a major depressive, manic, mixed, or hypomanic episode. Note: Episodes are demarcated either by partial or full remission for at least 2 months or a switch to an episode of opposite polarity (e.g., major depressive episode to manic episode).  Seasonal Pattern: (Table 15.1-27). ­ Patients with a seasonal pattern to their mood disorders tend to experience depressive episodes during a particular season, most commonly winter. ­ The pattern has become known as seasonal affective disorder (SAD), although this term is not used in DSM-IV-TR. ­ Two types of evidence indicate that the seasonal pattern may represent a separate diagnostic entity:  First, the patients are likely to respond to treatment with light therapy.- 39 -Page By Mohamed Abdelghani

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