2. Frequently the “mood elevation” in mania is “dysphoric” in which irritability dwarfs, the euphoric or expansive quality of mood.
1. The jolly state is often transient or absent
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2. Conceptually- opposite of depression, but can overlap
1. Depression ratings are often higher during mania than during depression
3. Manifestations of early stages of mood elevation are often subtle, culture bound and may appear more isolated than the pervasive disturbance associated with depression

4. Risk of suicide increases during manic episodes
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1. Thwarting a manic patient increases the potential for suicide and violence
2. The end of a manic episode is often extremely uncomfortable

1. Increased risk of substance abuse to sustain the high
2. Increased risk for suicide especially if mood state drops into depression
3. Patients are very poor reporters of mood elevation
1. Inter-rater reliability for mania is very high
2. inter-rater reliability for hypomania is very low
4. Not all manics are psychotic
5. Thought disorder is common in acute mania

1. 15-30% of acute manics exhibit Schneiderian first rank symptoms
2. About 50% show delusions, about 1/3 hallucinations
3. Variability extreme-clear to confused, with alternation
4. Differentiation from schizophreniform disorders may be impossible in acutely
6. Unipolar Mania

1. Rare, but no data indicate its a separate entity
2. Same risk of affective illness for first-degree relatives
3. Lower incidence of rapid cycling and suicide attempts
7. Mania can be a form of psychosis and may present with characteristic symptoms of thought disorder indistinguishable from schizophreniform disorder
8. Bipolar affective Disorder

1. Any history of Mania

2. Most have history of meeting criteria for Major depressive episodes
3. Always recurrent
9. Clinical Notes

1. Among bipolar patients, 10-20% present with a manic episode or history of such an episode
2. First onset of manic episode without prior depression is very rare after age 65
3. The hostility of manics is generally more dramatic than that of paranoid schizophrenia
4. Tearfulness, depressed mood, even suicidal ideation are not uncommon at the height of a manic episode or in the transition from mania to retarded depression
5. Time from 1st depressive episode to 1st manic episode is up to a decade or more; mode = 5-6 years. (Akiskal, APA III)
6. The differential diagnosis from schizophrenia
1. Long course with periods of normal or “supernormal” functioning favors BP disorder
2. Psychotic symptoms in affective disorder tend to occur at the height of mania and depth of depression
3. Poverty of speech content (vagueness, but not poverty of speech or laconic speech) and severe affective flattening tend to favor schizophrenia Dx
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4. Response to lithium or a TCA favors affective Dx
5. Positive DST and REM latency test, possibly blunted TRH test response can help identify affective disorder
6. Differential diagnosis form alcoholism
Comorbid alcohol abuse is common to many psychiatric illness, but sociopathy is the only diagnosis with a higher rate of comorbid alcoholism than bipolar illness. Alcohol abuse is considerably more likely to occur in association with mania than during depression.
The prognosis for alcoholism is better with comorbid bipolar illness than for alcoholism alone (Am J Psychi, 1995).

1. Diagnosis is bipolar illness if a single episode can be documented with
1. mania/hypomania independent of substance abuse or 2. with symptoms mood elevation clearly before substance abuse
2. Family hx is very useful
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10. Course of Illness:

1. Prior to first major mood episode nonaffective diagnoses are common
1. Anxiety Disorders
2. Elimination Disorder
3. Sleep Disorders
4. Disruptive Behavior Disorders
5. Substance abuse

2. Chronic with periods of acute illness between which recovery to baseline function
3. Follow-up and Recovery
1. Over 30-40 year follow-up suggested 50% of BP patients achieved a full recovery
2. A small percentage suffer severe deterioration.
3. Harrow et al suggest <25% have excellent outcome
4. If recurrent, depressive episodes became more frequent, with shorter intervals between them, as patient gets older.
5. Progressive sensitization vs clustering

4. Manic Episodes are typically mixed with elements of both depression and mania
1. Coexisting or rapid alternation (bad prognosis)
1. Nearly 40% remain ill >1.5 yrs (Keller et al)
2. About 40% of manic episodes meet criteria for mixed state
2. DSM IV requires 1 week with symptoms meeting both As formalized in DSM IV, the criteria for mixed episodes provides a standard which enhances reliability of the diagnosis. It is unclear, however, if the stringent criteria requiring symptoms sufficient to meet both full depression and mania is clinically different than simply having the quality of dysphoric mood during mania. Several studies suggest prognosis is worse if manic episode is accompanied by 2 or more depressed symptoms or simply has includes the quality of dysphoric mood. There are no studies directly comparing the prognosis or treatment response of mixed episodes defined strictly versus loosely.
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Many studies lump rapid cycling (especially of with short cycle length) with mixed episodes. This is reasonable since the reliability of diagnosing the onset and offset of short periods of dysphoria and mood elevation is probably quite low. If cycling length is on the order of 24 hrs it appears pointless to differentiate rapid cycling from mixed episodes. Such mixed episodes may represent an extreme form of rapid cycling

3. Mixed Episodes

1. Associated with secondary neuropsychiatric factors
1. Substance abuse
2. Subclinical drug toxicity
2. Higher prevalence among females
1. Winokur 1969, Murphy 1974, Krishnan 1983
3. Are mixed episodes the result of progressive worsening (kindling) ?

1. Typical of episodes of among Children and Adolescents
2. Mixed vs Pure
1. Over course of illness in 108 women (Dell’Osso 1990)
1. Median onset mania 30.6 yrs
2. Median onset mixed 39.2 yrs
2. Number of prior episodes not greater in Mixed (Prien 1988)
3. Greater number of prior hospitalizations for depression-(Post 1989) Family hx – (Dell’Osso 1990)
1. no difference – overall rate of affective illness
2. Rate of unipolar illness higher in relatives of Mixed
3. Rate of bipolar illness higher in relatives of Pure

11. Working with Bipolar patients

1. Understand that there is a person apart from the illness
2. Families/employers/friends tend to tolerate depression better than mania
3. Understand that mood is a filter coloring all experience

1. Consider the possibility of current pathological mood state
2. It is pointless to argue with a manic patient

Criterion AI: depressed mood.
2. B. During the same period of illness, there have been delusions or hallucinations for at least 2 weeks in the absence of prominent mood symptoms.
3. C. Symptoms that meet criteria for a mood episode are present for a substantial portion of the total duration of the active and residual periods of the illness.
4. D. The disturbance is not due to the direct physiological effects of a substance (eg, a drug of abuse, a medication) or a general medical condition.
5. Specify type:

1. Bipolar Type: if the disturbance includes a Manic or a Mixed Episode (or a Manic or a Mixed Episode and Major Depressive Episodes)
2. Depressive Type: if the disturbance only includes Major Depressive Episodes
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1. Evidence suggests its resemblance to Affective Disorders
1. No surprise since criteria require full affective syndrome
2. Can schizoaffective patients be distinguished from schizophrenics by high urinary phenylacetic acid levels (Sabelfi et al, 1989)?

15. III Clinical Notes

1. Clinical Characteristics of Depression
2. The principle problems
1. Distinguishing normal from pathological

2. Subtyping Depressive states
1. Reactive vs Endogenous
1. little empirical support for either concept
2. Psychotic vs Neurotic
1. Presence of psychotic features coded in DSM IV by fifth digit
3. Involutional Melancholia
1. Patients with involutional onset report more agitation, initial insomnia, somatization and hypochondriasis. (Brown 1984)
2. Genetically heterogeneous (Stenstedt 1959)
3. Same phenomenology seen at other times (Post 62, Angst 66, Weisman 79)
4. Unipolar vs Bipolar
1. Still considerable debate as to whether these are distinct. Goodwin and Jamison favor a continuum model
5. Primary vs Secondary
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1. Attractive idea but this distinction is without grounding or definition
2. DSM IV skirts the issue by defining secondary as “due to” a medical condition or substance use without saying how it can be determined when depression is “due to” another condition
3. Causes of Secondary Depression

1. Medical Illnesses
1. Damage to Brain Tissue
1. Stroke, trauma, subcortical dementias,MS, HIV
2. Endocrine/Humoral

1. Cushings, Addisons, Hypo/hyperthyroid, paraneoplastic (pancreatic CA), hyperparathyroidism, hyperprolactinemia
3. Latrogenic

Reserpine, steroids, propranolol, thiazides, methyldopa, barbiturates, ACTH, contraceptives, L-dopa, amphetamine, benzodiazepines, metoclopramide, cimetidine, spironolactone
2. Other psychiatric Illness

1. Substance Abuse
2. Anxiety Disorder
3. Eating Disorders
4. Psychotic Disorders

6. Biological (Magic) Markers
1. Urinary MHPG
2. Dexamethasone
3. Decreased REM Latency
4. TRH Stimulation Test
5. CSF 5-HIAA
6. Response to Sleep Deprivation
7. Course Specifiers

1. Melancholic
2. Atypical
3. Postpartum onset
4. Rapid Cycling
5. Seasonal Pattern

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 l-week period.
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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 (eg, a drug of abuse, a medication, or other treatment) or a general medical condition (eg, hyperthyroidism).

Note: Mixed-like episodes that are clearly caused by somatic antidepressant treatment (eg, medication, electroconvulsive therapy, light therapy) should not count toward a diagnosis of Bipolar i Disorder.

13. Simplified DSM IV Primary Mood Disorders

1. Unipolar
1. Major Depressive Disorder
1. Never manic or hypomanic
2. Single episode or recurrent MDE
2. Dysthymia
1. Period of chronic dysphoria or disinterest
1. Child or adolescent 1 year

2. Adult 2 years
2. During which
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1. more than half the days dysphoria or disinterest is present and at least 2 associated symptoms of depression
2. Never meets criteria for Depression
3. Any euthymic period is less than 8 weeks
4. Never manic or hypomanic
3. NOS
2. Bipolar
1. Bipolar type I

1. one or more manic episodes
2. Bipolar type II
1. Hypomania but never mania
2. Must have at least one MDE
3. Cyclothymia

1. Period with frequent hypomanic symptoms 1. Child or adolescent I year 2. Adult 2 years
2. During which
1. more than half the days too low or too high

• 2. Never meets criteria for Depression

• 3. Never criteria for mania

• 4. Any euthymic period is less than 8 weeks

4. NOS

C. The symptoms do not meet criteria for a Mixed Episode (see p. 335).
D. 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.

10. E. The symptoms are not due to the direct physiological effects of a substance (eg, a drug of abuse, a medication, or other treatment) or a general medical condition (eg, hyperthyroidism).

1. Note: Manic-like episodes that are clearly caused by somatic antidepressant treatment (eg, medication, electroconvulsive therapy, light therapy) should not count toward a diagnosis of Bipolar I Disorder.

2. This is a significant change from DSM III-R which stated
1. F. it cannot be established that an organic factor initiated and maintained the disturbance. NOTE: Somatic antidepressant treatment (eg, drugs, ECT) that apparently precipitates a mood disturbance should not be considered an etiologic organic factor.

11. Criteria for Hypomanic Episode*

1. 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.
2. 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 (eg, 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 (ie, 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
7. excessive involvement in pleasurable activities that have a high potential for painful consequences (eg, 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 (eg, a drug of abuse, a medication, or other treatment) or a general medical condition (eg, hyperthyroidism).
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Note: Hypomanic-like episodes that are clearly caused by somatic antidepressant treatment (eg, medication, electroconvulsive therapy, light therapy) should not count toward a diagnosis of Bipolar !1 Disorder.

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.
D. The symptoms are not due to the direct physiological effects of a substance (eg, a drug of abuse, a medication) or a general medical condition (eg, hypothyroidism).
E. The symptoms are not better accounted for by Bereavement, ie, 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.

9. Criteria for Manic Episode*

A. A distinct period of abnormally and persistently elevated, expansive, or irritable mood, lasting at least 1 week (or any duration if hospitalization is necessary).

1. 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 (eg, feels rested after only
3 Hours of sleep)
3. More talkative than usual or pressure to keep talking
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4. Flight of ideas or subjective experience that thoughts are racing
5. Distractibility (ie, 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
7. Excessive involvement in pleasurable activities that have a high potential for painful consequences (eg, engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments)
C. The symptoms do not meet criteria for a Mixed Episode (see p. 335).
D. 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.
Mood disorders information

1. Note: this now includes antidepressant induced episodes

5. Mood disorders Due to a General Medical Condition

1. characterized by a prominent and persistent disturbance in mood that is judged to be a direct physiological consequence of a general medical condition. (hypothyroidism, Cushings, frontal lobe tumor)

6. Mood Disorder Not Otherwise Specified

1. Included for coding disorders with mood symptoms that do not meet the criteria for any specific Mood Disorder and in which it is difficult to choose between Depressive Disorder Not Otherwise Specified and Bipolar Disorder Not Otherwise Specified (eg, acute agitation).

7. DSM IV criteria for mood disorder episodes

8. Criteria for Major Depressive Episode*

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.

1. 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 (eg, feels sad or empty) or observation made by others (eg, 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 (eg, 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.
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D. The symptoms are not due to the direct physiological effects of a substance (eg, a drug of abuse, a medication) or a general medical condition (eg, hypothyroidism).

E. The symptoms are not better accounted for by Bereavement, ie, 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.

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.

D. The symptoms are not due to the direct physiological effects of a substance (eg, a drug of abuse, a medication) or a general medical condition (eg, hypothyroidism).

E. The symptoms are not better accounted for by Bereavement, ie, 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.

5. The Nosology of DSM IV
A core concept in DSM IV is the distinction between the episodes of abnormal mood (eg depression, mania, hypomania and mixed) from the illnesses characterized by these episodes.
1. Current Nosology

1. DSM IV has Four Mood disorder categories and a residual category
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The diagnostic criteria for current episodes (mania, hypomania, depression and mixed) are distinguished from the criteria illnesses characterized by the longitudinal pattern of episodes. Explicit in the DSM IV is the concept that a primary mood disorder is only one of possible causes that can produce a mood episode. Other common causes of mood episodes include medical disorders, substance abuse disorders, and other psychiatric illness.
2. Unipolar Mood Disorders

1. Major Depressive Disorder
2. Dysthymia
3. Depressive Disorder NOS

3. Bipolar Disorders

1. Bipolar I

1. Last episode can be specified

1. mixed
2. manic
3. Hypomanic
4. depressed

2. Bipolar II
3. Cyclothymia
4. Bipolar disorder NOS

1. Classical formulation = anger turned inward
2. Freud 1915

1. Mourning and Melancholia
1. “The disturbance of self-regard is absent in mourning; but otherwise the features are the same”
2. “Moreover, the exciting causes due to environmental influences are, so far as we can discern them at all, the same for both conditions.”.

2. Kraepelin’s synthesis

1. Set the stage for the current classification system. The initial division of mad patients or “dements” was based on the age of onset. Those that developed psychotic symptoms late in life (senile dementia) were placed under the care of Dr. Alzheimer. Those who were ill earlier in life were distinguished into two groups based on the course of illness. Patients with a chronic course of unremitting deterioration were diagnosed “dementia praecox” and those considered to recover completely between their episodes of illness were noted to have prominent mood symptoms and received the diagnosis “manic-depressive insanity”.
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2. Basic Characteristics of Kraepelin’s Mood disorder
1. Usually early age of onset
2. Prominent mood symptoms
3. Recurrent Episodes
4. Periods of recovery
5. Variable Courses

3. Leonhard

1. The Classification of Endogenous Psychosis
1. Found Kraepelin’s classification wholly inadequate and described 56 separate psychotic illnesses including several varieties of illness which alternated between specific affective states (eg “anxiety-euphoria psychosis”). Such bipolar illnesses were separated form the “monopolar” types. Subsequent research failed to validate Leonhard’s illnesses except for the division of manic depressive insanity into unipolar and bipolar depression based on the occurrence of manic episodes during the course of the illness.

1. “A kind of dotage without a fever, having for his ordinary companions fear and sadness, without any apparent occasion”
2. Sadness among symptoms but not the defining characteristic.
3. 3 Subtypes: Primary: Generalized: Hypochondriacal
4. Clinico-anatomical (19 th century)

1. Associated overt signs of illness with anatomical lesions. Failure to identify lesions in patients with mental illness had two major consequences;

1. The concept of neurosis gradually changed from a label implying tissue pathology to a psychodynamic formulation.

2. In the absence of etiological classification the basis of nosology was descriptive classification

1. Under the descriptive system separate clusters of mental functions could become diseased separately.

1. Intellectual
2. Emotional

3. Volitional

5. Falret 1854
1. Memoire sur la Folie Circulaire
1. Described cyclical course of mood including “folie a double forme”

1. History records recognition of profound disturbances of emotions in its most ancient accounts of the human condition.
1. Gilgemesh the first single-case report
2. Hippocrates Melancholia = Humoral Imbalance (5th century BC)

1. Ancient concepts of melancholia bear little correspondence to its modern meaning or to the idea of depression or even mood. The historical idea of melancholia most nearly conveys the same meaning as “madness”. Hippocrates observed symptoms of delirium in patients suffering from quartan malaria and noted their darkened skin. He ascribed this over abundance of black bile, melancholia. This term like depression became nonspecific as it became associated with character traits, grief, and illness.

1. Divine Affliction
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1. The severity of suffering was interpreted even by many otherwise physicianly experts as evidence of punishment by the gods rather than the result of a lesion like other disease states. Galen (2nd century) attempted to correct this asserting his belief that the causes of mental illness was based on the same principles as other medical illness. Unfortunately through the middle ages the prevailing view (adopted by the church) followed Malleus Maleficarum (1486, The Hammer of witchcraft).

2. Burton’s Anatomy of Melancholia (1621)
1. Sadness among symptoms but not the defining characteristic.