Chapter V Mental and behavioural disorders (F00-F99)

Mood [affective] disorders (F30-F39)

This block contains disorders in which the fundamental disturbance is a change in affect or mood to depression (with or without associated anxiety) or to elation. The mood change is usually accompanied by a change in the overall level of activity; most of the other symptoms are either secondary to, or easily understood in the context of, the change in mood and activity. Most of these disorders tend to be recurrent and the onset of individual episodes can often be related to stressful events or situations. F30 Manic episode All the subdivisions of this category should be used only for a single episode. Hypomanic or manic episodes in individuals who have had one or more previous affective episodes (depressive, hypomanic, manic, or mixed) should be coded as bipolar affective disorder (F31.-). Incl.: bipolar disorder, single manic episode
F30.0 Hypomania

A disorder characterized by a persistent mild elevation of mood, increased energy and activity, and usually marked feelings of well-being and both physical and mental efficiency. Increased sociability, talkativeness, over-familiarity, increased sexual energy, and a decreased need for sleep are often present but not to the extent that they lead to severe disruption of work or result in social rejection. Irritability, conceit, and boorish behaviour may take the place of the more usual euphoric sociability. The disturbances of mood and behaviour are not accompanied by hallucinations or delusions.
F30.1 Mania without psychotic symptoms

Mood is elevated out of keeping with the patient's circumstances and may vary from carefree joviality to almost uncontrollable excitement. Elation is accompanied by increased energy, resulting in overactivity, pressure of speech, and a decreased need for sleep. Attention cannot be sustained, and there is often marked distractibility. Self-esteem is often inflated with grandiose ideas and overconfidence. Loss of normal social inhibitions may result in behaviour that is reckless, foolhardy, or inappropriate to the circumstances, and out of character.
F30.2 Mania with psychotic symptoms

In addition to the clinical picture described in F30.1, delusions (usually grandiose) or hallucinations (usually of voices speaking directly to the patient) are present, or the excitement, excessive motor activity, and flight of ideas are so extreme that the subject is incomprehensible or inaccessible to ordinary communication. Mania with:

mood-congruent psychotic symptoms mood-incongruent psychotic symptoms

Manic stupor
F30.8 Other manic episodes F30.9 Manic episode, unspecified

Mania NOS F31 Bipolar affective disorder A disorder characterized by two or more episodes in which the patient's mood and activity levels are significantly disturbed, this disturbance consisting on some occasions of an elevation of mood and increased energy and activity (hypomania or mania) and on others of a lowering of mood and decreased energy and activity (depression). Repeated episodes of hypomania or mania only are classified as bipolar. Incl.: manic-depressive:

illness psychosis reaction

Excl.: bipolar disorder, single manic episode (F30.-) cyclothymia (F34.0)

F31.0 Bipolar affective disorder, current episode hypomanic

The patient is currently hypomanic, and has had at least one other affective episode (hypomanic, manic, depressive, or mixed) in the past.
F31.1 Bipolar affective disorder, current episode manic without psychotic symptoms

The patient is currently manic, without psychotic symptoms (as in F30.1), and has had at least one other affective episode (hypomanic, manic, depressive, or mixed) in the past.

F31.2 Bipolar affective disorder, current episode manic with psychotic symptoms

The patient is currently manic, with psychotic symptoms (as in F30.2), and has had at least one other affective episode (hypomanic, manic, depressive, or mixed) in the past.
F31.3 Bipolar affective disorder, current episode mild or moderate depression

The patient is currently depressed, as in a depressive episode of either mild or moderate severity (F32.0 or F32.1), and has had at least one authenticated hypomanic, manic, or mixed affective episode in the past.
F31.4 Bipolar affective disorder, current episode severe depression without psychotic symptoms

The patient is currently depressed, as in severe depressive episode without psychotic symptoms (F32.2), and has had at least one authenticated hypomanic, manic, or mixed affective episode in the past.
F31.5 Bipolar affective disorder, current episode severe depression with psychotic symptoms

The patient is currently depressed, as in severe depressive episode with psychotic symptoms (F32.3), and has had at least one authenticated hypomanic, manic, or mixed affective episode in the past.
F31.6 Bipolar affective disorder, current episode mixed

The patient has had at least one authenticated hypomanic, manic, depressive, or mixed affective episode in the past, and currently exhibits either a mixture or a rapid alteration of manic and depressive symptoms. Excl.: single mixed affective episode (F38.0)
F31.7 Bipolar affective disorder, currently in remission

The patient has had at least one authenticated hypomanic, manic, or mixed affective episode in the past, and at least one other affective episode (hypomanic, manic, depressive, or mixed) in addition, but is not currently suffering from any significant mood disturbance, and has not done so for several months. Periods of remission during prophylactic treatment should be coded here.
F31.8 Other bipolar affective disorders

Bipolar II disorder Recurrent manic episodes NOS

F31.9 Bipolar affective disorder, unspecified

F32 Depressive episode

In typical mild, moderate, or severe depressive episodes, the patient suffers from lowering of mood, reduction of energy, and decrease in activity. Capacity for enjoyment, interest, and concentration is reduced, and marked tiredness after even minimum effort is common. Sleep is usually disturbed and appetite diminished. Self-esteem and selfconfidence are almost always reduced and, even in the mild form, some ideas of guilt or worthlessness are often present. The lowered mood varies little from day to day, is unresponsive to circumstances and may be accompanied by so-called "somatic" symptoms, such as loss of interest and pleasurable feelings, waking in the morning several hours before the usual time, depression worst in the morning, marked psychomotor retardation, agitation, loss of appetite, weight loss, and loss of libido. Depending upon the number and severity of the symptoms, a depressive episode may be specified as mild, moderate or severe. Incl.: single episodes of:

depressive reaction psychogenic depression reactive depression

Excl.: adjustment disorder (F43.2) recurrent depressive disorder (F33.-) when associated with conduct disorders in F91.- (F92.0)
F32.0 Mild depressive episode

Two or three of the above symptoms are usually present. The patient is usually distressed by these but will probably be able to continue with most activities.
F32.1 Moderate depressive episode

Four or more of the above symptoms are usually present and the patient is likely to have great difficulty in continuing with ordinary activities.
F32.2 Severe depressive episode without psychotic symptoms

An episode of depression in which several of the above symptoms are marked and distressing, typically loss of self-esteem and ideas of worthlessness or guilt. Suicidal thoughts and acts are common and a number of "somatic" symptoms are usually present.

Agitated depression Major depression Vital depression

single episode without psychotic symptoms

F32.3 Severe depressive episode with psychotic symptoms

An episode of depression as described in F32.2, but with the presence of hallucinations, delusions, psychomotor retardation, or stupor so severe that ordinary social activities are impossible; there may be danger to life from suicide, dehydration, or starvation. The hallucinations and delusions may or may not be mood-congruent. Single episodes of:

major depression with psychotic symptoms psychogenic depressive psychosis psychotic depression reactive depressive psychosis

F32.8 Other depressive episodes

Atypical depression Single episodes of "masked" depression NOS

F32.9 Depressive episode, unspecified

Depression NOS Depressive disorder NOS F33 Recurrent depressive disorder A disorder characterized by repeated episodes of depression as described for depressive episode (F32.-), without any history of independent episodes of mood elevation and increased energy (mania). There may, however, be brief episodes of mild mood elevation and overactivity (hypomania) immediately after a depressive episode, sometimes precipitated by antidepressant treatment. The more severe forms of recurrent depressive disorder (F33.2 and F33.3) have much in common with earlier concepts such as manicdepressive depression, melancholia, vital depression and endogenous depression. The first episode may occur at any age from childhood to old age, the onset may be either acute or insidious, and the duration varies from a few weeks to many months. The risk that a patient with recurrent depressive disorder will have an episode of mania never disappears completely, however many depressive episodes have been experienced. If such an episode does occur, the diagnosis should be changed to bipolar affective disorder (F31.-). Incl.: recurrent episodes of:

depressive reaction psychogenic depression reactive depression

seasonal depressive disorder Excl.:

recurrent brief depressive episodes (F38.1)

F33.0 Recurrent depressive disorder, current episode mild

A disorder characterized by repeated episodes of depression, the current episode being mild, as in F32.0, and without any history of mania.
F33.1 Recurrent depressive disorder, current episode moderate

A disorder characterized by repeated episodes of depression, the current episode being of moderate severity, as in F32.1, and without any history of mania.
F33.2 Recurrent depressive disorder, current episode severe without psychotic symptoms

A disorder characterized by repeated episodes of depression, the current episode being severe without psychotic symptoms, as in F32.2, and without any history of mania. Endogenous depression without psychotic symptoms Major depression, recurrent without psychotic symptoms Manic-depressive psychosis, depressed type without psychotic symptoms Vital depression, recurrent without psychotic symptoms
F33.3 Recurrent depressive disorder, current episode severe with psychotic symptoms

A disorder characterized by repeated episodes of depression, the current episode being severe with psychotic symptoms, as in F32.3, and with no previous episodes of mania. Endogenous depression with psychotic symptoms Manic-depressive psychosis, depressed type with psychotic symptoms Recurrent severe episodes of:

major depression with psychotic symptoms psychogenic depressive psychosis psychotic depression reactive depressive psychosis

F33.4 Recurrent depressive disorder, currently in remission

The patient has had two or more depressive episodes as described in F33.0-F33.3, in the past, but has been free from depressive symptoms for several months.
F33.8 Other recurrent depressive disorders F33.9 Recurrent depressive disorder, unspecified

Monopolar depression NOS

F34 Persistent mood [affective] disorders Persistent and usually fluctuating disorders of mood in which the majority of the individual episodes are not sufficiently severe to warrant being described as hypomanic or mild depressive episodes. Because they last for many years, and sometimes for the greater part of the patient's adult life, they involve considerable distress and disability. In some instances, recurrent or single manic or depressive episodes may become superimposed on a persistent affective disorder.
F34.0 Cyclothymia

A persistent instability of mood involving numerous periods of depression and mild elation, none of which is sufficiently severe or prolonged to justify a diagnosis of bipolar affective disorder (F31.-) or recurrent depressive disorder (F33.-). This disorder is frequently found in the relatives of patients with bipolar affective disorder. Some patients with cyclothymia eventually develop bipolar affective disorder. Affective personality disorder Cycloid personality Cyclothymic personality
F34.1 Dysthymia

A chronic depression of mood, lasting at least several years, which is not sufficiently severe, or in which individual episodes are not sufficiently prolonged, to justify a diagnosis of severe, moderate, or mild recurrent depressive disorder (F33.-). Depressive:

neurosis personality disorder

Neurotic depression Persistent anxiety depression Excl.: anxiety depression (mild or not persistent) (F41.2)
F34.8 Other persistent mood [affective] disorders F34.9 Persistent mood [affective] disorder, unspecified

F38 Other mood [affective] disorders Any other mood disorders that do not justify classification to F30-F34, because they are not of sufficient severity or duration.
F38.0 Other single mood [affective] disorders

Mixed affective episode

F38.1 Other recurrent mood [affective] disorders

Recurrent brief depressive episodes

F38.8 Other specified mood [affective] disorders

F39 Unspecified mood [affective] disorder Incl.: Affective psychosis NOS

INTRODUCTION The introduction of the American Psychiatric Association Diagnostic and Statistical Manual (DSM-III in 1980 and DSM-IV in 1994) and the World Health Organization International Classification of Diseases (ICD-10 in 1992) has resulted in development of operational criteria for mental and behavioral disorders (see Figures 2.1 and 2.2). This in turn has made it possible to perform large crosssectional epidemiologic surveys to compare prevalence rates across various cultures and communities, and between primary and secondary care settings. INCIDENCE AND PREVALENCE The frequency of a condition is generally reported in terms of incidence and prevalence. The incidence is the rate at which new cases occur in a population during a specified period. If the population at risk is constant then: I=N/(P (I, incidence; N, number of new cases; P, population at risk; T, time during which cases were ascertained) By contrast, the prevalence of a disease is the proportion of a population that are cases at a point in time. When a disorder occurs intermittently, a single assessment in time gives a point prevalence, which could underestimate the frequency of the condition. A better measure is one that uses a stated time period (e.g. 1 month, 6 months, 12 months or a lifetime) and assesses the frequency of cases within that time. CASENESS To be included in the disease count a person must be diagnosed as being a case. Diagnosis requires a clear definition of the condition, in the form of operational criteria against which to compare a patients symptoms (such as those included in the DSM-IV and ICD-10 criteria). Some medical conditions show a clear dichotomy between case and non-case (e.g. Down

syndrome), but most fall somewhere along a continuum of severity (see Figure 2.3). Much of psychiatric diagnosis is at this level, ranging in intensity from minimal subthreshold symptoms to extreme and disabling symptoms. Epidemiologic research is hindered by a number of methodologic problems, which should be considered when comparing incidence and prevalence rates. The testretest reliability can be poor, as the recollection of affect is often inaccurate and memory and concentration problems are features of most mental disorders. The assessment instruments developed within the construct of the diagnostic categories of DSM and ICD may lack sensitivity in primary care and community settings, where psychiatric problems are frequently less severe and persistent and many cases are subthreshold, i.e. do not fulfil the criteria for a full diagnosis. GENDER Approximately 15% of the general population report depressive symptoms, with 10% of primary care consultations being due to depressive disorders1. Most crosscultural community surveys have found major depressive disorder to be about twice as prevalent in women as in men, the lifetime prevalence being approximately 20% compared to 10%, respectively2. There is some evidence that women develop more complex and severe clinical pictures, and probably a more troublesome course3. The reason for this gender difference is unclear, although greater childcare responsibilities and fewer opportunities for paid employment may be important factors. However, men are known to report fewer problems, and seek help for emotional problems less frequently. AGE In the elderly there appears to be a leveling out of the gender difference for major depression, although the overall prevalence of depressive symptoms appears to increase with age (see Figure 2.4). Several studies suggest a rising incidence of depression in younger age groups, particularly in young men, which may be linked to the relative rise in suicide rates in this age group when compared to the declining rates in the general population4. Major depression in childhood is no longer considered rare, the point prevalence in children lying in the range 0.52.5%5. Depression is notably more common in adolescents than in younger children, having an average period prevalence of around 34%6. COMORBIDITY Depression and anxiety usually occur together, both in community and clinical samples. Approximately twothirds of those with a lifetime history of major depression have a lifetime history of another psychiatric

disorder, and an even higher proportion of those with anxiety have multiple previous disorders. Some of the comorbidity of anxiety and depression is artifactual, due to the categorical approach to psychiatric diagnosis. The use of a more dimensional approach, in which the severity of individual symptoms and signs is described rather than the current categorical approach, which involves counting symptoms would reduce this apparent comorbidity. Patients with significant coexisting depressive and anxiety symptoms have a poorer prognosis with greater impairment, greater persistence of symptoms, increased use of health service resources and an increased risk of suicidal behavior. REFERENCES
1. Ormel J,Tiemens B. Depression in primary care. In Honig A, van Praag HM, eds. Depression: Neurobiological, Psychopathological and Therapeutic Advances. Chichester, UK: John Wiley, 1997 2. Patel V. Cultural factors and international epidemiology. Br Med Bull 2001;57:3345 3. Angst J. Epidemiology of depression. In Honig A, van Praag HM, eds. Depression: Neurobiological, Psychopathological and Therapeutic Advances. Chichester, UK: John Wiley, 1997 4. Fombonne E.True trends in affective disorders. In: Cohen P, Slomkoski C, Robins LN, eds. Historical and Geographical Influences on Psychopathology. New Jersey: Laurence Erlbaum, 1999:11539 5. Harrington R. Epidemiology. In: Harrington R, ed. Depressive Disorder in Childhood Adolescence. Chichester, UK: John Wiley, 1993 6. Fombonne E. The epidemiology of child and adolescent depression psychiatric disorders: recent developments

Dorland, W.A. 2002. Kamus Kedok teran Dorland, edisi: 29. J a k a r t a : E G C . Halaman:20302031
Goldman HH (editor). Review of General Psychiatry, 5th Edition, Lange Medical Books/McGraw-Hill: New York NY, 2000.

MAJOR DEPRESSION Depression is one of the most prevalent medical disorders and has been recognized as a distinct pathological entity from early Egyptian times. In spite of this, the disorder is commonly undiagnosed and undertreated. Common usage of the word depression stems principally from the attempts of the nineteenth-century psychiatrist Emil Kraepelin to introduce a term that would have greater diagnostic specificity than melancholia. Currently, the term melancholia denotes major depressive disorder with changes in endogenous or vegetative function, eg, disturbances of sleep, appetite, and libido. Although clinicians, throughout most of this century, have attempted to subclassify the syndrome on the basis of symptoms and causes, many of the subclassifications proved to be invalid or unreliable. For example, the distinction between depressions that were reactive and those that were nonreactive or endogenousie, not precipitated by psychosocial stresshas not proved to

be of predictive value. Such judgments in any case are highly subjective and depend on how detailed a history is obtained and how much weight is assigned by the patient or clinician to the changes that routinely occur in life. Distinctions on the basis of age have likewise proved suspect, with recent research indicating that depression during the involutional period is qualitatively no different from that experienced during any other stage. Symptoms & Signs A variety of studies have distinguished depressed individuals with prominent psychomotor retardation and anhedonia from those who evidence psychomotor activation, guilt, anxiety, and, occasionally, delusional thinking. The number and severity of somatic symptoms generally increase along with the severity of depression. Separating major depressions according to whether they are endogenous or autonomous has not been found to be useful, either in predicting drug response or in improving assessments of general risk. Individuals may in fact show endogenous features in one episode and not in another. The character of depressive symptoms depends to a large extent on the severity of the disorder. In the most severe cases (1015%), patients may present with an extensive paranoid or nihilistic delusional system and the experience of hallucinations, usually self-deprecatory in content and consonant with the underlying mood state. Mood-incongruent psychotic features are less frequently present. Because such individuals have more psychomotor disturbance and generally respond poorly to antidepressant medication, some investigators have considered psychotic depression as a separate entity and not simply a severe variant of major depression. Depression occurs at any age and can present with primary symptoms that do not involve obvious mood change. Depression in children may be difficult to diagnose. Because of cognitive and linguistic developmental changes that occur in childhood, emotional states are experienced and projected differently. In P.276 older people, the most significant symptom may be a change in cognitive function. The term pseudodementia has been applied to a state clinically identical to irreversible senile dementia but that resolves with antidepressant treatment. Recent research questions the utility of this distinction, since an unremitting course and lack of pharmacological response of senile dementia are far from confirmed. In masked depression, a condition in which there is no apparent mood change, the course of illness, prognosis, and response to treatment are the same as those associated with classical major depression. Depression is one of the most common missed diagnoses in the general medical clinic. It may be associated with a primary disorder such as an endocrinopathy, neoplasm, or viral infection, but it more commonly occurs independently in the context of a panoply of multisystemic somatic complaints. When the disease state is thought to be causal, a diagnosis of mood disorder due to a general medical condition should be given, rather than major depression. Natural History There is great variation in the clinical presentation and course of major depression. As the individual patient's history accumulates, recurrent episodes tend to develop a cyclic pattern of presentation, so that better judgments about the probable future course can be made. Depression can occur at any age, but the average age at onset is between 30 and 40 years. In general, the earlier the age at onset, the more likely it is that there will be a recurrence. Symptoms develop either gradually over a period of many months or more dramatically over a

shorter period, in many cases following a significant loss or episode of stress, although this is not necessary. If untreated, the depressive episode may resolve spontaneously over a period of weeks to months or may become chronic and remain essentially unchanged over a period of years. The mean duration for treated episodes is approximately 20 weeks. Although most patients with major depression respond well to somatic treatment, uncontrolled studies have revealed that recovery from major depressive disorder is not as good as once thought. Only about 50% of patients are completely recovered at 1-year follow-up. The prognosis worsens with increased severity of symptoms at onset, less acute onset, and occurrence of the acute episode superimposed on an underlying state of chronic depression. The risk of relapse after recovery from major depressive disorder is high for a short periodabout 25% relapse within 12 weeks. For individuals with recurrent episodes, it is difficult to predict how soon another episode can be expected. The presence of a chronic underlying depression or a history of three or more depressive episodes significantly increases the risk of early relapse. In addition, there is evidence that the interval between episodes becomes shorter as the individual ages. Chronic depression is associated with major decrements in functional abilities and results in significant societal burden. The total annual costs of depression have been estimated at 44 billion dollars. Depression has also been shown to be a major risk factor for the development of cardiovascular disease and death after a myocardial infarction. At least 2030% of patients with major depression and no history of mania will experience a manic or hypomanic episode later in life. Factors positively correlated with eventual bipolar outcome include pharmacological induction of mania, a history of postpartum depression, early onset (less than 25 years of age), and symptoms of hypersomnia and psychomotor retardation. Differential Diagnosis Depression occurs concomitantly with a number of different disease states, such as pancreatic and bronchogenic carcinoma, hypothyroidism, Cushing's syndrome, and cerebrovascular disease. When the mood state is felt to be etiologically related to the medical condition, the diagnosis of major depression should not be given. As noted, depression and dementia, particularly in the elderly, may be confused. However, patients with dementia may develop major depression as well. In some individuals, depression occurs in association with seasonal change, giving rise to the term seasonal mood disorder. Such individuals have experienced improvement in mood through phase advance alteration of their sleep-wake cycle and through the administration of several hours daily of high-intensity light, usually during morning hours. A regulatory disturbance of pineal gland function and melatonin secretion has been hypothesized in these patients, and the syndrome itself has been conceptualized as an evolutionary remnant of the mammalian hibernation cycle. In DSM-IV, a seasonal pattern may be a specific diagnostic feature of either bipolar disorder or recurrent major depression. Schizophrenia commonly presents with significant depressive symptoms, either during the acute phase or shortly following resolution of psychotic symptoms. In such cases the diagnosis of depressive disorder not otherwise specified is added to the primary diagnosis. The differential diagnosis between major depression with psychosis and schizophrenia with depressive signs is exceedingly difficult and can best be made by considering aspects of the patient's premorbid history and a family history of psychiatric disorder. Because a diagnosis of schizophrenia requires a duration of at least 6 months, the date of onset is important. In dysthymic and cyclothymic disorders, aspects of the depressive syndrome may occur but are not of sufficient intensity or duration to meet the criteria for major depression. It should be remembered, however, that major depression can occur in these or other disorders

P.277 as an independent, superimposed entity and should be recorded as such. The diagnosis of dysthymic disorder should not be given if an episode of major depression emerges in the first 2 years, however. Patients with bipolar disorder, mixed type, may likewise exhibit features of severe depression but will also present manic symptoms. Grief syndromes often present with behavioral and physiological changes identical to those observed in major depression. Major depression should not be diagnosed until it is determined that the reaction is either too severe or too prolonged to be explained as simple bereavement. Comorbidity with anxiety disorders and substance abuse is common. Prognosis In individual cases, estimates of the degree of recovery and the likelihood of staying well depend mostly on the patient's age at onset, the number of previous episodes, and the response to somatic and psychosocial treatment. Many individuals have only one depressive episode in a lifetime. The likelihood of recurrence is dramatically increased with the onset of a second episode and continues to rise slightly with each additional episode, eventually reaching a statistical plateau. In cases in which suicidal preoccupation is recurrently noted in successive episodes and in which profound delusional content is noted, the prognosis for recovery is generally poor. Illustrative Case The patient was a surgeon referred by an internist for evaluation of complaints of fatigue and hand tremor. During outpatient evaluation, the patient said that 4 months previously he began noticing a significant worsening of manual dexterity during surgery. He attributed his difficulties to a fine tremor that he demonstrated for the examiner. He felt guilty about several patients who had put their faith in him and had suffered for it. He was sure that people in the hospital were making disparaging comments about his condition, though he could offer no specific examples. He had become reluctant to schedule operations but at the same time said that his decreased income was mainly attributable to fewer referrals from colleagues and the word getting out. Although this was the first occurrence of this kind, he felt that his whole career had been a sham and that his previous accomplishments were undeserved. He could see no medical or psychiatric solution to his difficulties and expressed an intention to retire, although he was only 47 years old and not financially able to do so. Although the patient had full health and disability insurance coverage, he expressed great concern about the impending hardship to his family from medical expenses and his failure to earn a good income. This concern magnified even trivial expenditures; eg, he felt he could no longer buy a morning paper without jeopardizing his son's college education. He reported poor appetite and a weight loss of 15 lb in less than 2 months. He reluctantly acknowledged that he and his wife had not had sexual relations in 4 months because of his impotence. He was unable to read professional journals or popular reading matter. Direct questioning revealed early morning awakening, but he said this was not a problem. Despite a strong feeling that all of his troubles were related to the hand tremor, he agreed to enter the hospital for a trial of antidepressant medication. On the ward, he received a combination of drug treatment and individual and group therapy. After 10 days of drug treatment (imipramine, 200 mg orally daily), he began sleeping better and eating regularly. He continued to complain of depression but

admitted to an increase in energy level, a decrease in tremulousness, and an ability to maintain an erection. A week later, he began to express an interest in returning to work and initiated plans for discharge. Epidemiology Although mood disorders are widely acknowledged to be common, their prevalence is difficult to determine because of differences in diagnostic procedures and criteria. Assessments of depressive symptomsie, intense, pervasive, and almost daily feelings of sadness or disappointment that affect normal functioningshow lifetime prevalence rates of 920%. (The relationship of such subjective assessments to the objective diagnosis of major depression is not known.) When more stringent criteria for major depression are used, prevalence of major depression is 3% for men and 49% for women. The lifetime risk is 812% for men and 2026% for women. These figures also may be high, since they are largely dependent on subjective evaluations of individuals who have not sought treatment. There has been a progressive increase in rates of depression in successive birth cohorts throughout this century as well as a progressively earlier age of onset. About 1220% of persons experiencing an acute episode develop a chronic depressive syndrome, and up to 15% of patients who have depression for more than 1 month commit suicide.

Etiology & Pathogenesis A. Biochemical Factors Genetic studies and studies on the effect of specific antidepressant drugs have led to the conclusion that most cases of recurrent major depression have some biological basis. This does not mean, however, that psychological factors have no role in symptom formation or in precipitation of episodes of depression of lesser severity. Family and genetic studies indicate that the risk rate among first-degree relatives of individuals suffering from major depression (unipolar) is approximately two to three times the risk in the general population. This, it should be noted, is approximately P.278 half the rate reported among first-degree relatives of individuals suffering from bipolar illness. The concordance rate is about 11% for dizygotic twins and approaches 40% for monozygotic twins. Bio- logical parents of adopted probands have a much greater prevalence of mood disorder than adoptive parents. The most prominent hypotheses generated to account for the actual mechanism of the mood disorder focus on regulatory disturbances in the monoamine neurotransmitter systems, particularly those involving norepinephrine and serotonin (5-hydroxytryptamine). It has also been hypothesized that depression is associated with an alteration in the acetylcholine-adrenergic balance and characterized by a relative cholinergic dominance. In addition, there are suggestions that dopamine is functionally decreased in some cases of major depression. Because the central nervous system monoamine neurotransmitter systems are widely distributed and involved in tonic regulation of autonomic functions, arousal, movement, sleep, aggression, and other vegetative functions, they are particularly well suited for their hypothesized role. Original reports suggesting that patients with endogenous depression experienced either decreased noradrenergic

or serotonergic activity now appear to be overly simplistic. All the monoamine neurotransmitter systems are interrelated and subject to compensatory adaptation to perturbation over time. In addition, the discovery that many neuropeptides and hormones may serve as neurotransmitters and neuromodulators in certain contexts has underscored the complexity of the neural regulation of mood (see Chapter 6). A significant number of patients have evidence of either increased or decreased noradrenergic function, as reflected by urinary levels of 3-methoxy-4-hydroxyphenylglycol (MHPG), the primary metabolite of central nervous system nonadrenergic function. Other major studies have pointed to a decrease in serotonergic activity in certain subgroups, as measured by levels of 5hydroxyindoleacetic acid (5-HIAA), the principal metabolite of serotonergic activity in the brain, and 5-hydroxytryptamine (5-HT2A) receptor binding. Depletion of tyrosine or tryptophan has also been shown to cause depression in vulnerable individuals. Most current hypotheses of neurotransmitter function in altered mood states have focused on changes in receptor sensitivity and second messenger systems. With a few exceptions long-term antidepressant treatment has been found to be associated with reduced postsynaptic -adrenergic receptor sensitivity and enhanced postsynaptic serotonergic and cyclic adenosine monophosphate activity. In an effort to integrate these data, investigators have recently focused more on genomic regulation, specifically the role of transcription factors as causal agents. Several specific abnormalities in neuroendocrine regulation may represent evidence of either primary disturbance in hypothalamic-pituitary control or secondary alteration in neurotransmitter function in limbic sites. The most consistent finding is that many patients with severe depressive disorder have an excess secretion of cortisol from the adrenal cortex stimulated by increased release of corticotropin-releasing factor from the hypothalamus. This is not simply a stressrelated phenomenon, because the actual number of secretory episodes is increased, principally in the early morning hours when the system is normally quiescent. Many cortisol hypersecretors also have levels of norepinephrine, MHPG, and epinephrine in plasma and urine that are several times higher than normal. In addition to alterations in the pituitary-adrenal axis, elevation in serum triiodothyronine and thyroxine have been reported, as has a significant blunting of the response of thyroid-stimulating hormone to an infusion of thyrotropin-releasing hormone. Reports of changes in growth hormone, prolactin, luteinizing hormone, and testosterone regulation in major depressive disorder are contradictory. From a neurophysiological perspective, the most replicable finding is that sleep in severe depression is characterized by decreased total sleep, decreased rapid eye movement (REM) latency (ie, sleep time from onset of sleep until the first epoch of REM sleep), increased REM density (ie, ratio of REM activity to REM time), and decreased stage 4 sleep. Sleep electroencephalography does not differentiate subgroups of depressed patients but may help predict a positive response to antidepressant medication. Immunological studies have identified a variety of subtle alterations in depression, including change in lymphocyte subsets, response to mitogen, natural killer cell activity, and cytokine regulation. Neuroimaging studies have found a variety of abnormalities in prefrontal cortex and cingulate gyrus and in periventricular white matter in geriatric patients suffering from depression. B. Psychosocial Factors Although psychosocial stress may play a role in the precipitation of a major depressive episode and shape the particular constellation of symptoms noted, current research indicates that environmental factors as such do not cause severe depressive episodes. However, depressed

individuals are often unable to accept the concept of biological vulnerability and remain convinced that they themselves or changes in their environment are principally responsible for their mood state. Self-doubt, guilt, and an overriding sense of worthlessness will often lead to disruption in relationships with friends and family and to a withdrawal from workactions that have understandable long-term effects on mood. Chronic depression and depressive personality traits may thus emerge as the psychological and social concomitants, and sequelae of recurrent biological depressive states. Histrionic P.279 and hostile character traits are often noted, as is a long history of difficulty in maintaining stable interpersonal relations. The presence of a personality disorder does not affect the symptom profile but does presage a worse outcome. The observation that many patients with depression have similar distinctive personality traits led Freud and other psychoanalytic writers to see clinical depression as a psychologically reparative mechanism. The loss of a love object and the consequent psychic injury could be overcome only by self- punishment in which the internalized object was devalued. Freud maintained that ego development depended on successful resolution of object loss. Through a process of narcissistic identification, the ego became the target of revengeful aggressive treatment intended for the original object. Depression thus emerges as the construct of guilt over anger toward an ambivalently perceived (loved, hated) object. Other psychoanalytic writers have elaborated and adapted Freud's views, focusing on depression as an ego response to helplessness rather than internalized anger. Such formulations are undoubtedly useful for conceptualizing the origin of milder depressive episodes in individuals who are still socially functional and for understanding symptom formation in more severe depressive states. However, biological vulnerability is probably an essential prerequisite to the expression of major depressive disorder. More recently, investigators have stressed the cognitive distortions that dramatically prolong the morbid mood state. The most common cognitive distortions involve negative interpretation of experience, a negative evaluation of the self, and pessimism about the future. Thus, a reverberating loop is established in which a dysphoric affect can give rise to distorted perceptions that in turn exacerbate the dysphoria. This formulation is helpful in understanding the tenacity with which depressed patients seem to cling to the depressive experience even in the face of apparent reward, success, and support. One cognitive theory based on animal studies is called learned helplessness. In this formulation, individuals in stressful situations in which they are unable to prevent or alter an aversive stimulus (ie, physical or psychic pain) withdraw and make no further attempts to escape even when opportunities to improve the situation become available. Another theory postulates that a reduction in the rate of positive reinforcement is the principal cause of depression. Low self-esteem is a consequence of the inability of depressed patients to engage in successful goalseeking behaviors and a resultant low rate of positive reinforcement. Cognitive and behavioral approaches to the depressive syndrome seem to be more useful for conceptually understanding the psychosocial effects of the depressive state and for planning psychotherapy than for explaining the origin of such episodes. An individual carrying a biological predisposition for recurrent depressive episodes may, for example, successfully negotiate biologically vulnerable periods during times of little conflict or stress. Treatment A. Biomedical Therapies

A trial of antidepressant medication is indicated for most individuals with major depression, particularly if melancholic features are present (Table 20-1). Most patients with depression are either undertreated or inappropriately treated. Benzodiazepines, which may exacerbate the problem, are prescribed much more often than tricyclic agents. Premature withdrawal of antidepressant medication and symptomatic relapse are also unfortunately common. Drug selection should be based on the patient's general medical condition, the drug's side effects, and a personal or family history of therapeutic response to a specific agent. About 70% of patients with major depression respond favorably to antidepressant medication. Most cases of poor response result either from the patient's failure to take the medication as prescribed or from inadequate dosage. Selective serotonin reuptake inhibitors (SSRIs) have largely displaced tricyclic antidepressants as the initial treatment choice because of their better tolerated side effect profile. However, because the blood level from a given dosage varies as much as 30-fold in different individuals, in cases of nonresponse to certain antidepressant drugs it is useful to measure plasma drug levels, even in patients receiving maximal doses. The value of plasma levels is most clear with nortriptyline and desipramine. Although useful for titrating dosage into a general range, variations in blood levels within that range do not correlate well with clinical response. Clear therapeutic benefit usually is noticed 1421 days after starting treatment, although earlier and later responses are not uncommon. In general, objective signs of improvement (increased appetite, weight gain, improved sleep and affect, reduced agitation, increased purposeful activity) are noted before subjective improvement. A drug of a different class should be considered for patients whose symptoms do not improve after 6 weeks of medication with adequate blood levels. Alternatively, another drug may be added, such as liothyronine, lithium, buspirone, or a monoamine oxidase (MAO) inhibitor. A trial either of an MAO inhibitor alone or of lithium carbonate might be considered at this point. MAO inhibitorsphenelzine or tranylcypromine can be drugs of first choice for individuals who present with prominent anxiety associated with depression or who complain specifically of fatigue, hypersomnia, and weight gain rather than weight loss. Although lithium does not have as specific an antidepressant effect as more traditional antidepressant agents, it may help patients with clear periodicity of P.280 depressive recurrences and is a better prophylactic agent than traditional antidepressant agents. How long maintenance treatment should be continued after acute symptoms have subsided is not always clear; current opinion indicates that indefinite treatment at the acute dosage is warranted if relapse is to be avoided. Patients with very severe depressions and prominent delusional features are relatively refractory to traditional antidepressant treatment. The response often can be enhanced by addition of an antipsychotic agent. Electroconvulsive therapy should be considered in such cases and in cases of nondelusional major depression resistant to drug therapy. Most controlled studies have shown that electroconvulsive therapy is at least as effective as antidepressant medication in the treatment of major depression and often produces a much faster recovery. There are few contraindications to the use of electroconvulsive therapy, and side effects are limited to memory loss for the period just before and after treatment (see Chapter 30). In the past several years a series of studies have shown that transcranial magnetic stimulation, a procedure used originally

in neurological diagnosis, can have an antidepressant effect. This intervention is currently being evaluated further. B. Psychosocial Therapies Psychotherapy is often indicated for major depression, particularly to improve social functioning following remission of acute symptoms. Controlled studies have indicated that the combination of psychotherapy and antidepressant medication is more effective than either used alone. It should be noted, however, that in most moderate to severe cases of major depression, drug therapy alone is significantly better than psychotherapy alone. Many psychotherapeutic approaches have been utilized, but therapies that focus on the depressed patient's interpersonal functioning and cognitive distortions appear to be the most productive. Insight therapy is made difficult by the depressed patient's tendency to interpret therapeutic suggestions as criticism. Cognitive therapy is often didactic in nature and may profitably include homework assignments in which the patient is asked to examine critically and test erroneous assumptions deriving from the depressive experience. For example, a patient may say, I fail at everything I try to do. Asking that patient to keep a log of daily tasks and document the outcome of each effort affords the therapist an effective means of challenging the patient's derogatory self-image. Testimony from others who are able to state that the tasks were performed satisfactorily can be sought if necessary (see Chapter 33). The involvement of family and spouse should not be neglected in treatment planning. This may take several forms, including education about the illness, emotional support, and consideration of interpersonal issues. Although prepubertal children with major depression who receive drug treatment usually show a return to normal functioning in areas such as school performance, ongoing deficits in peer and family relationships frequently continue and require specific intervention.
Review of General Psychiatry - 5th Edition