Bipolar disorder with frequent mood episodes in the national comorbidity survey replication (NCS-R).

Virtually nothing is known about the epidemiology of rapid cycling bipolar disorder (BPD) in community samples. Nationally representative data are reported here for the prevalence and correlates of a surrogate measure of DSM-IV rapid cycling BPD from the National Comorbidity survey Replication (NCS-R), a national survey of the US household population. DSM-IV disorders were assessed in the NCS-R with the WHO Composite International Diagnostic Interview (CIDI). Although the CIDI did not assess rapid cycling, it did assess the broader category of 12-month BPD with frequent mood episodes (FMEs), having at least four episodes of mania/hypomania or major depression in the 12 months before interview. Roughly one-third of NCS-R respondents with lifetime DSM-IV BPD and half with 12-month BPD met criteria for FME. FME was associated with younger age-of-onset (of BP-I, but not BP-II) and higher annual persistence (73% of the years since first onset of illness with an episode) than non-FME BPD. No substantial associations of FME vs non-FME BPD were found with socio-demographics, childhood risk factors (parental mental disorders, other childhood adversities) or comorbid DSM-IV disorders. However, FME manic episodes had greater clinical severity than non-FME episodes (assessed with a fully structured version of the Young Mania Rating Scale) and FME hypomanic episodes had greater role impairment than non-FME episodes (assessed with the Sheehan Disability Scales). Whether these indicators of severity merely reflect attenuated effects of rapid cycling or independent effects of sub-threshold rapid cycling warrants further study given the high proportion of lifetime cases who met criteria for FME.

Epidemiology of affective disorders.

Data from recent epidemiological studies involving psychosocial risk factors for affective disorders are reviewed. The results of these studies are divided into the categories of depressive symptoms, bipolar depressive disorder, and nonbipolar depressive disorder. When the data are examined using these categories, remarkable consistency in psychosocial risk factors for depressive symptoms and nonbipolar depressive disorder is observed, suggesting possible continuity between these conditions. Psychosocial risk factors for bipolar disorder differ substantially from those identified for depressive symptoms and nonbipolar depressive disorder and, therefore, provide further support for the bipolar-nonbipolar distinction.

Protecting subjects and fostering research. Striking the proper balance.

Bonnie reminds us of the heritage and limitations of human subjects research. He points out that over the years, the protection of human subjects in research has enjoyed progress, experienced false starts, and endured inflated expectations. Both he and Elliott call attention to the fact that IRB review rarely probes how researchers propose to deal with impairments to subjects' decision-making capacities. We agree to IRBs should be encouraged to rethink their roles. But, as Bonnie argues, this requires a systematic review of the roles and functions of IRB rather than ad hoc adjustments by individual institutional IRBs. His proposal that IRBs should be encouraged to be more vigilant and through in their monitoring of research is sound, especially if the subjects are vulnerable or the research is risky. A strength of Bonnie's review is that it suggests both specific ways to test competency and a range of options for IRBs to ensure that vulnerable subjects are protected from overzealous or overreaching researchers. His historical review and normative proposals are objective, balanced, and thoughtful. Elliott's critique seems to single out psychiatric research with depressed patients as a special problem area. Although his title emphasizes severely depressed patients, he sometimes appears to neglect the fact that depression ranges across a spectrum from mild to severe. Elliott's point is well taken that severely depressed patients who are clearly incompetent should not, unless proper safeguards are provided, be enrolled in research. But his analysis falters because his position does not in the end respect personal autonomy.

The relationship of personality to affective disorders.

Although characterologic constellations such as obsessionalism, dependency, introversion, restricted social skills, and maladaptive self-attributions are popularly linked to the pathogenesis of depressive disorders, the evidence in support of this relationship remains modest. Indeed, many of these attributes may reflect state characteristics woven into the postdepressive personality. Current evidence is strongest for introversion as a possible premorbid trait in primary nonbipolar depressions. By contrast, driven, work-oriented obsessoid, extroverted, cyclothymic, and related dysthymic temperaments appear to be the precursors of bipolar disorders. Other personalities, while not necessarily pathogenic in affective disorders, nevertheless may modify the clinical expression of affective disorders and their prognosis.

Family and genetic studies of affective disorders.

This article summarizes discussion, conclusions, and recommendations of participants in a National Institute of Mental Health-sponsored workshop dealing with major issues in family and genetic studies of affective disorders. Key up-to-date findings in the field are reviewed with emphasis on areas of agreement. Remaining controversies and problems are identified, and a set of overall conclusions and recommendations for future research activities in the field is presented.

NIMH clinical research branch collaborative program on the psychobiology of depression.

This is a report on the history and implications of the collaborative effort that evolved from the 1969 National Institute of Mental Health conference on the psychobiology of depression. The major issues identified at that time were the need to (1) assess relative validities of current systems of nosology and (2) retest critical biological hypotheses concerning the etiology and nature of the depressive disorders. Research was required that would be multidisciplinary and involve clinical settings treating diverse types of depression. The objectives and the nature of the biological and clinical collaborative programs that were designed to address these problems are described. These unique programs, initiated in the early 1970s, currently span research on nosology, genetics, neurochemistry, neuroendocrinology, and psychosocial factors. Although these studies are still in the early stages, they have resulted in significant methodologic developments in diagnosis, descriptive psychopathology, and biological measurements.

The validation of the concept of endogenous depression. A family study approach.

Depressive illnesses are subdivided into endogenous and nonendogenous types in psychiatry throughout the world. We used one method of validating this nosologic subdivision: the determination of the extent to which the disorder is familial. Rates of depression were examined in 2,942 first-degree relatives of 566 individuals diagnosed as having unipolar major depressive disorder. Because no single definition of endogenous depression is universally accepted, four different methods for defining endogenous depression were compared: the Newcastle Scale, the Research Diagnostic Criteria, DSM-III, and the definition of "autonomous depression" proposed by investigators at Yale University (New Haven, Conn). In general, no matter which definition was used, the relatives of the patients with endogenous illness did not have higher rates of depressive illness than those of the nonendogenous group. The Newcastle Scale was the most sensitive in picking up familial transmission of recurrent unipolar depression. The results of this investigation suggest that longitudinal approaches should be added to cross-sectional approaches for the best definition of endogenous depression.

Situational major depressive disorder.

Fifty-seven patients with situational major depression diagnosed by the Research Diagnostic Criteria were compared with 72 subjects with nonsituational major depression on demographic, clinical, and psychosocial variables. The situational patients tended to be younger and had fewer prior episodes of depression and fewer hospitalizations. No differences were found in categories of life events, in overall clinical picture, in social supports, or in family history.

Premorbid personality assessments of first onset of major depression.

This is a report on personality traits associated with the first onset of major depression in a sample of high-risk subjects. The subjects are the first-degree relatives, spouses, and their controls of patients with affective disorders. None of these subjects had any history of mental disorder as of their initial evaluation. In the subsequent six years, 29 subjects had a first onset of major depression. These first onset subjects were compared with 370 subjects who continued to be free of illness during the six-year follow-up. Personality traits were assessed at the initial evaluation (ie, before the onset of depression in subjects with first onset) by means of scales from five self-report inventories. Lower emotional strength and resiliency significantly differentiated the first onset from the never ill group; overall differences were not found on measures of interpersonal dependency or extraversion. Age was a significant predictor of first onset, both alone (younger age predicted first onsets) and in interaction with personality measures. Among younger subjects (17 to 30 years of age), personality variables did not significantly discriminate between the two comparison groups. Among older subjects (31 to 41 years of age), however, decreased emotional strength, increased interpersonal dependency, and increased thoughtfulness were associated with first onset of depression.

Personality and depression. Empirical findings.

The Clinical Studies of the National Institute of Mental Health--Clinical Research Branch Collaborative Program on the Psychobiology of Depression offer an opportunity to clarify the relationship between personality and depression. Thirty-one female patients with primary nonbipolar major depressive disorder were assessed diagnostically using the Schedule for Affective Disorders and Schizophrenia and completed a battery of standard self-report personality inventories when they were completely symptom free. Their personality scale scores were compared with those of female relatives who had recovered from the same type of disorder, those of female relatives with no history of psychiatric illness, and published scale norms. Compared with the normal population, both groups of recovered depressives were introverted, submissive, and passive, with increased interpersonal dependency but normal emotional strength. Comparison to never-ill relatives yielded similar results except that the never-ill relatives had scores reflecting extraordinary emotional strength.

The familial transmission of bipolar illness.

As part of the National Institute of Mental Health Collaborative Program on the Psychobiology of Depression study, data were collected on 2225 first-degree relatives of 612 probands. We analyzed 187 families of bipolar patients (149 probands with a diagnosis of bipolar I disorder and 38 with a diagnosis of schizoaffective, manic subtype). Using traditional genetic methods, the morbid risk of bipolar illness in relatives was found to be 5.7% in the relatives of bipolar probands as contrasted with 1.1% in the relatives of probands with major depression. These values compared closely with those obtained using survival analysis. Relatives of probands with early onset were found to have a greater risk than relatives of probands with late onset. The sex of the relative, the sex of the proband, or the subtype of the proband (bipolar I or schizoaffective bipolar) did not influence the risk in the relative. The age at onset was found to be accelerated with birth cohort, with individuals born in more recent cohorts having an earlier onset. Multifactorial analysis found significant heterogeneity for sex-specific sibling correlations (with the brother-sister correlation smaller than the same-sexed correlations), and path analysis estimated transmissibility of liability to be 71%. The mixed model, which allows for a single major locus with a multifactorial background, gave evidence for the presence of a major locus when controlling for the effects of birth cohort and age at onset. However, this evidence is tempered when comparing the mixed model with a more general transmission model.

Reliability of lifetime diagnosis. A multicenter collaborative perspective.

It is important to determine the reliability of lifetime diagnosis in a nonpatient population, for this type of diagnostic data and this type of sample are used in many genetic, epidemiological, and nosological studies. We examined the reliability of lifetime diagnosis when the Schedule for Affective Disorders and Schizophrenia-Lifetime Version and Research Diagnostic Criteria were used to interview ill and well relatives of probands in the National Institute of Mental Health Collaborative Study of the Psychobiology of Depression. Subjects were interviewed three times, so data are available concerning both short- and long-interval test-retest reliability. Short-interval test-retest reliability was excellent for both diagnoses and symptoms. Reliability was also quite high in the long-interval test-retest study. We conclude that it is possible to make lifetime diagnoses reliably in a nonpatient population.

Low levels and lack of predictors of somatotherapy and psychotherapy received by depressed patients.

We examined the treatment of 338 patients with nonbipolar major depressive disorders during the first eight weeks after entry into the National Institute of Mental Health-Clinical Research Branch Collaborative Program on the Psychobiology of Depression: Clinical Study. Of the 250 entered as inpatients, 31% received either no antidepressant somatotherapy or very low or unsustained levels, and only 49% received at least 200 mg of imipramine hydrochloride (or its equivalent) for four consecutive weeks. Of these patients, 19% received less than 30 minutes of psychotherapy per week. Among the 88 who entered as outpatients, 29% received no antidepressant somatotherapy; another 24% received very low or unsustained levels; only 19% received at least 200 mg of imipramine hydrochloride or its equivalent for four consecutive weeks. Of these patients, 52% received less than 30 minutes of psychotherapy per week. Only a few clinical factors were found to be predictive of treatment intensity. Very large differences in the amount and type of treatment across the five collaborating university centers do not appear to be related to differences in patient characteristics.

Time to recovery, chronicity, and levels of psychopathology in major depression. A 5-year prospective follow-up of 431 subjects.

The course of illness of 431 subjects with major depression participating in the National Institute of Mental Health Collaborative Depression Study was prospectively observed for 5 years. Twelve percent of the subjects still had not recovered by 5 years. There were decreasing rates of recovery over time. For example, 50% of the subjects recovered within the first 6 months, and then the rate of recovery declined markedly. Instantaneous probabilities of recovery reflect that the longer a patient was ill, the lower his or her chances were of recovering. For patients still depressed, the likelihood of recovery within the next month declined from 15% during the first 3 months of follow-up to 1% to 2% per month during years 3, 4, and 5 of this follow-up. The severity of current psychopathology predicted the probability of subsequent recovery. Subjects with moderately severe depressive symptoms, minor depression, or dysthymia had an 18-fold greater likelihood of beginning recovery within the next week than did subjects who were at full criteria for major depressive disorder. Many subjects who did not recover continued in an episode that looked more like dysthymia than major depressive disorder.

A randomized, placebo-controlled 12-month trial of divalproex and lithium in treatment of outpatients with bipolar I disorder. Divalproex Maintenance Study Group.

BACKGROUND: Long-term outcomes are often poor in patients with bipolar disorder despite treatment; more effective treatments are needed to reduce recurrences and morbidity. This study compared the efficacy of divalproex, lithium, and placebo as prophylactic therapy. METHODS: A randomized, double-blind, parallel-group multicenter study of treatment outcomes was conducted over a 52-week maintenance period. Patients who met the recovery criteria within 3 months of the onset of an index manic episode (n = 372) were randomized to maintenance treatment with divalproex, lithium, or placebo in a 2:1:1 ratio. Psychotropic medications were discontinued before randomization, except for open-label divalproex or lithium, which were gradually tapered over the first 2 weeks of maintenance treatment. The primary outcome measure was time to recurrence of any mood episode. Secondary measures were time to a manic episode, time to a depressive episode, average change from baseline in Schedule for Affective Disorders and Schizophrenia-Change Version subscale scores for depression and mania, and Global Assessment of Function scores. RESULTS: The divalproex group did not differ significantly from the placebo group in time to any mood episode. Divalproex was superior to placebo in terms of lower rates of discontinuation for either a recurrent mood episode or depressive episode. Divalproex was superior to lithium in longer duration of successful prophylaxis in the study and less deterioration in depressive symptoms and Global Assessment Scale scores. CONCLUSIONS: The treatments did not differ significantly on time to recurrence of any mood episode during maintenance therapy. Patients treated with divalproex had better outcomes than those treated with placebo or lithium on several secondary outcome measures.

Personality attributes and affective disorders.

To determine the personality characteristics associated with affective disorders the authors administered a battery of self-report personality inventories to a sample of hospitalized affective patients when their manifest symptoms had abated. Patients were instructed to answer according to their premorbid personalities. The personality characteristics assessed in the 73 depressive and 24 manic patients included neuroticism and extraversion from the Maudsley Personality Inventory, obsessional pattern, hysterical pattern, and oral pattern from the Lazare-Klerman-Armor Personality Inventory, obsessional state and trait from the Leyton Obsessionality Inventory, and solidity, stability, and validity from the Marke-Nyman Temperament Survey. Depressive patients demonstrated more neuroticism, introversion, and obsessionality than manic patients or normal individuals. The manic patients differed from normal persons only on obsessionality.

The Diagnostic Interview for Depressive Personality.

OBJECTIVE: The development of a new structured interview for depressive personality disorder is described. METHOD: A literature search yielded 32 traits associated with depressive personality; these traits were then used to develop the interview. Interrater reliability for the interview was tested in an initial group of 16 patients with longstanding depressive personality traits. Data from a second group of 67 subjects--54 with a possible clinical diagnosis of depressive personality and 13 normal volunteers--were used to examine the interview's psychometric properties and to modify its content. Factor analysis of the traits in the interview and modification of the instrument's structure was carried out on the basis of data from a third group of 526 subjects who were participating in a large epidemiologic study of mood disorders. RESULTS: The Diagnostic Interview for Depressive Personality, which emerged from this process, assess 30 personality traits that were shown to have satisfactory interrater reliability (kappa = 0.67), test-retest reliability (kappa = 0.41), and diagnostic reliability (kappa = 0.62). A cutoff score of 42 (from a total possible score of 60) on the interview offers a useful threshold for diagnosis. CONCLUSIONS: This interview provides a reliable method for assessing depressive personality traits and establishing the diagnosis of depressive personality disorder.

Neurotic depressions: a systematic analysis of multiple criteria and meanings.

Neurotic depression, the most commonly used psychiatric diagnosis, has multiple meanings that are often used interchangeably in clinical practice. The authors identify six different meanings of neurotic depression and present data from a study of 90 depressed inpatients to determine how many patients met several different criteria; 16 patients met four sets of criteria. The overlap that exists between the different meanings is higher than chance alone but not sufficiently high to allow complete interchangeability. Until new diagnostic classes are developed, the authors recommend that the term "neurotic depression" no longer be used clinically because of its vagueness.

A review of the depressive personality.

A depressive type of personality disorder has been described by both German phenomenologists and psychoanalysts and has been used by clinicians for years. Although this personality type has been included in standard international nosologic systems (ICD-9), it has never been recognized in DSM. This literature review identifies and explores the issues relevant to the possible inclusion of such a category--an axis II personality disorder linked to axis I depressive disorder--in the upcoming DSM-IV.

The persistent risk of chronicity in recurrent episodes of nonbipolar major depressive disorder: a prospective follow-up.

The authors report on the course of illness in 101 patients who were in an episode (the "index episode") of major depressive disorder when they entered a clinical research study, recovered from that episode, and then relapsed into a new episode (the "first prospective episode") of the disorder. They found a 22% probability that these patients' first prospective episode would last at least 1 year, similar to the 21% rate of chronicity previously reported for the index episode. A long prior episode, older age, and low family income were found to predict chronicity in the first prospective episode.