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Seven percent (19 of 275) of children and adolescents not ascertained for seeking treatment received a DSM-III diagnosis of alcohol or drug use disorder. Their entire families were recruited into a research program designed to study the risk to offspring of parental psychopathology. The ages of those diagnosed were between 12 and 18 years. The drug and alcohol use disorders had a mean duration of 2 years, and the adolescents who remitted had a high likelihood of developing subsequent psychopathology. These adolescents also showed high rates of other psychiatric disorders. A high rate of alcoholism was found among their parents.

Data concerning 331 subjects participating in a longitudinal study on anxiety disorders were collected over the first 6 months of the study. Preliminary analyses of somatic treatment according to diagnoses and study site were conducted. The comorbidity of one anxiety disorder with other DSM-III-R diagnoses and other types of anxiety disorders was extensive. Patients with panic disorder received significantly more treatment with a benzodiazepine than patients without panic disorder. Fewer than five percent of the sample were treated with a monoamine oxidase inhibitor. Comorbid depression increased the likelihood of treatment with a newer non-MAOI (non-monoamine oxidase inhibitor), nontricyclic antidepressant. Results suggest a strong effect of treatment site on the pharmacotherapy offered.

Although knowledge of the long-term course and outcome of bulimia nervosa is critical to the effective management of the bulimic patient, research in this area is still in its infancy. Comparisons between existing outcome studies are complicated by differences in research design and methods, a lingering confusion over the definition of terms such as recovery and relapse, and the possibility of multiple forms of bulimia nervosa with varying outcomes. Nonetheless, these studies agree that bulimia nervosa is a chronic disorder, characterized by high rates of relapse and persistent subclinical symptomatology. Future investigations into the course and outcome of bulimia nervosa should focus on the derivation of a universally acceptable terminology and the identification of clinical and psychosocial variables predicting recovery.

Objective: This study sought to describe, the natural history of major depressive disorder in a large group of nonclinical subjects. In particular, the analysis determined demographic and clinical risk factors for the recurrence of major depressive disorder., Method: Relatives, comparison subjects (matched to relatives for age and sex), and spouses of affectively ill probands underwent structured clinical assessments before and after a 6-year interval., Results: Of 396 individuals who had had only major depressive disorder that ended before the initial evaluation, 33.8% (N = 134) developed a new episode during the 6-year follow-up period. Youth, but not sex, was an important demographic risk factor. The presence of minor depression at the time of initial evaluation and the number of symptoms recalled from the worst previous episode were additional clinical risk factors. At the initial evaluation, 200 other subjects had described a previous history of both major depressive disorder and a nonaffective mental disorder. When compared to the subjects who recalled only a history of major depressive disorder, these subjects were more likely to have been in an episode of chronic intermittent depression at the initial evaluation and to recall a greater number of episodes as well as a greater number of symptoms in the worst episode. A history of a nonaffective mental disorder significantly increased the risk of relapse into major depressive disorder., Conclusions: These findings agree well with a recent review of clinically based follow-up studies. Thus, youth and a history of nonaffective illness are important risk factors for the recurrence of major affective disorder in a broad variety of settings.

In 1988, the MacArthur Foundation Research Network on the Psychobiology of Depression convened a task force to examine the ways in which change points in the course of depressive illness had been described and the extent to which inconsistency in these descriptions might be impeding research on this disorder. We found considerable inconsistency across and even within research reports and concluded that research on depressive illness would be well served by greater consistency in the definition change points in the course of illness. We propose an internally consistent, empirically defined conceptual scheme for the terms remission, recovery, relapse, and recurrence. In addition, we propose tentative operational criteria for each term. Finally, we discuss ways to assess the usefulness of such operational criteria through reanalysis of existing data and the design and conduct of new experiments.

Little is known about the occurrence and course of alcohol problems in patients with affective syndromes treated in psychiatric facilities. We have shown previously that a high proportion of such patients abused alcohol. In a 5-year follow-up of patients in the initial study, a large majority had a remission of their alcohol problems lasting at least 6 months, although many of these patients had subsequent relapses. Using survival analyses, we found that alcohol dependence indicators, previous chronicity of alcohol problems, and a diagnosis of schizoaffective disorder predicted poor outcome (specifically, longer time to remission of the alcohol problems). However, these factors were unrelated to receiving alcohol-specific treatment during the 5 years. Severity of social/occupational alcohol problems did not predict poor outcome, but did predict alcohol-specific treatment (detoxification, rehabilitation, Alcoholics Anonymous [AA], or Antabuse).

Investigations of bulimia nervosa have focused primarily on adult samples, although bulimia nervosa commonly has its onset in adolescence. Pediatricians are often questioned about its etiology, course, and treatment. In an attempt to provide pediatricians with answers, we integrate findings from recent epidemiological and treatment studies with a clinical report of 18 women who developed bulimia nervosa during their teens and sought treatment at our eating disorders clinic.

This article reports on the treatment received by 38 adolescents during an episode of major depression which had a median duration of 4 months. The one subject who received any pharmacologic treatment was prescribed an antianxiety agent. Sixteen percent received psychotherapy. These results are consistent with evidence from studies of adults indicating that depression is underrecognized and undertreated. An important caveat is that the small sample size limits the generalizability of these findings. Moreover, which medication should be prescribed when a diagnosis of depression is made is not yet known with certainty, as literature reviews indicate that more controlled trials of psychotherapeutic and psychopharmacologic treatments for adolescents with depression are needed to better understand the efficacy of treating depressed adolescents.

Bipolar affective disorder, previously known as manic depression, is a major public health problem affecting approximately 1% of the U.S. population. Despite the considerable emotional, psychological, and economic cost of this disorder, relatively little research has focused on developing alternative maintenance treatments for bipolar patients. The authors review the epidemiology, course, diagnosis, and current treatment options for those patients with bipolar disorder, then suggest areas for further research.

Most studies report the lifetime prevalence of major depressive disorder to be higher among women than men. One possible explanation is that this finding is the result of the diagnostic criteria used, in particular the inclusion of criterion symptoms associated with depressed mood. The number of criterion symptoms required for a diagnosis were varied and applied to 2163 first-degree relatives of affectively disordered probands of the NIMH Collaborative Study of the Psychobiology of Depression. Results indicated that differences between men and women in number of symptoms reported could not account for the difference in rates of depression. Women had a greater number of associated symptoms only at higher symptom levels, suggesting an excess of women only above a diagnostic threshold. Thus, findings supported a true difference in rates of major depressive disorder rather than a general trend for women to remember or report more criterion symptoms.

Expressed emotion (EE) refers to a set of emotional aspects of speech for which ratings have been derived. Seven independent studies have established that higher EE ratings in the relatives of patients with schizophrenia predict higher rates of relapse in these patients and two studies have established an association of higher EE in spouses with relapse of depression in their mate. There are no previous studies of parental EE as a predictor of childhood affective disorder or other disorders not in the schizophrenia spectrum. In this study we investigated the relationship between the level of maternal EE and the incidence of DSM-III affective disorder (major depression or mania or dysthymia), substance abuse, or conduct disorder in 273 children. We found that a higher degree of maternal expressed emotion was associated with a three-fold increase in a child's risk (odds multiplier) for having at least one of the following diagnoses: depressive disorder (major depression or dysthymia), substance abuse, or conduct disorder. This increased risk acts in addition to the increased risk of child diagnosis associated with parental affective illness. Research and clinical implications are discussed.

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.

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.

Thirty women who sought treatment at an eating disorders clinic in a general hospital and were diagnosed as having a current episode of bulimia nervosa were followed prospectively to assess the course of eating behaviors and other psychopathology. At intake, all 30 met DSM-III criteria for bulimia nervosa, and 57% met Research Diagnostic Criteria for an affective disorder. After 6 months of followup, 33% had recovered from the bulimic episode, and 24% had recovered from the affective disorder. One subject had recovered from both disorders. In subjects with an affective disorder at intake, the affective disorder had little effect on the time to recovery from bulimia nervosa, and recovery from bulimia nervosa had little effect on the time to recovery from the affective disorder.

Risk of relapse into an affective episode was high in the months immediately after recovery from a major depressive disorder (MDD) in 141 subjects with nonbipolar depression, without a preexisting dysthymic disorder. The probability of relapse then declined steadily during the duration of the follow-up (median follow-up, 62 weeks from recovery). In patients entering the study during their first affective episode, the Research Diagnostic Criteria secondary subtype of MDD and an older age of onset predicted a significantly greater likelihood of relapse. Three or more prior episodes of depression predicted a significantly shorter time to the first and second prospectively observed relapses and, thus, a significantly greater likelihood of subsequent multiple affective episodes.

In this study we assess the reliability of rating past psychiatric symptoms and lifetime diagnoses in a currently ill population using the SADS and RDC. Five raters from different centers interviewed 25 subjects in a short-interval test-retest design. Subjects had a wide diversity of affective and non-affective diagnoses and high levels of manifest psychopathology. Our results demonstrate that it is possible for raters from different research centers to reliably rate lifetime diagnoses and previous symptoms. Two important exceptions to the high reliability are the lifetime diagnoses of hypomania and the recurrent unipolar subtype of major depressive disorder, and we alert clinicians and researchers to be cautious when diagnosing these conditions. We conclude that the next step in measuring reliability should be a long-interval test-retest design with separate interviews conducted at the later assessment, one by the original rater and the other by a blind rater.

The mechanisms involved in the excretion of the histamine H2-receptor antagonist cimetidine are as yet incompletely understood. The purpose of this study was to examine the interaction of cimetidine with incubated slices of dog kidney cortex. The results of time and concentration-dependent experiments by using 3H-labeled cimetidine demonstrated that the drug was accumulated without metabolism against a concentration gradient by a saturable process. Inhibition of uptake by cyanide and by incubation under a nitrogen atmosphere indicated energy dependence. Uptake of cimetidine by active cationic transport was likely inasmuch as both cyanine 863 and quinine blocked accumulation. However, a probenecid-sensitive component, accounting for about 20% of steady-state accumulation, also was identified. The lack of inhibitory action of p-aminohippuric acid and the cationic nature of the cimetidine molecule suggest the probenecid-sensitivity was not related to the renal organic anion mechanism. Further, probenecid inhibition was not due to a generalized cellular toxicity because maximally inhibitory concentrations of probenecid did not interfere with uptake of the cation tetraethylammonium.

Ninety-one patients with panic attacks limited historically to depressive episodes had more severe depressive symptoms and were less likely to recover during a 2-year follow-up than 417 depressed patients who did not have panic attacks. Family study data clearly distinguished another 15 patients with panic disorder and secondary depression; interviewed relatives of panic disorder patients were significantly less likely to have primary depression and significantly more likely to have various anxiety disorders. These data support the hierarchical system by which many of the contemporary diagnostic systems separate panic disorder and major depression.

The influence of the clinically depressed state on personality assessment was evaluated by comparing self-report personality inventories of patients while clinically depressed and at follow-up 1 year later. The authors examined two groups from the National Institute of Mental Health (NIMH)-Clinical Research Branch Collaborative Program on the Psychobiology of Depression: Clinical Studies--patients whose symptoms had completely remitted and those who had not recovered. The clinically depressed state strongly influenced assessment of emotional strength, interpersonal dependency, and extraversion. Assessment of rigidity, level of activity, and dominance did not change after symptomatic recovery.

Analyses of data from the NIMH-CRB Collaborative Depression Study on age at onset of Major Depressive Disorder (MDD) in 1144 directly interviewed siblings of patients with major affective disorder show a strong secular trend toward increased lifetime risk and earlier onset in successive cohorts of birth since 1930. The proportionate increases in the instantaneous probabilities (hazard) of onset of MDD for each one year difference in year of birth were 5% for brothers and 7% for sisters. Age-period-cohort analysis suggests a powerful period effect may be responsible for this secular trend in rates of MDD, with rates of onset for siblings between 15 and 50 years of age doubling between the 1960s and 1970s. Possible artifacts are investigated.

After a description of threshold models of familial transmission based on an underlying continuous liability distribution, family data from the NIMH-CRB Collaborative Psychobiology of Depression Program-Clinical are described. No sex differences are found for bipolar illness, whereas female relatives have an increased rate of primary unipolar illness when compared to male relatives. This effect persists when relatives are classified according to recurrence, current illness, onset within the last 10 years, and treatment. Moreover, a cohort effect is present in the data and indicates a sex ratio close to one in the young cohort (less than or equal to 25). We considered the transmission of illness from parent to offspring by using survival analysis to examine the proportion of ill brothers and sisters of probands according to the affection status of parents. A maternal effect is found, with the mother having a greater influence on the liability of offspring of either sex. This is at odds with the notion that males and females have identical liabilities, but females have a lower threshold reflecting acknowledgement of more symptoms, etc. However, the mean difference in liability between the sexes may be due to systematic biological/cultural differences, with parental transmission contributing to variation about their means.

As part of the National Institute of Mental Health-Clinical Research Branch Collaborative Program on the Psychobiology of Depression Clinical Study, 2,289 relatives of 523 probands with affective disorder were interviewed with the Schedule for Affective Disorders and Schizophrenia and diagnosed for major depressive disorder by the Research Diagnostic Criteria. Data were analyzed using life-table and survival methods. The findings suggest a progressive increase in rates of depression in successive birth cohorts through the 20th century and an earlier age at onset of depression in each birth cohort. A predominance of female depressives was found in all birth cohorts but the magnitude of female-male differences fluctuated over the decades. The existence of these trends is reported to stimulate further research. These findings are discussed in terms of possible gene-environment interactions. However, no conclusive causal inferences can be drawn pending further investigation.

Of 316 patients with a major depressive disorder who were followed for between 6 months and 2 years, 80 (25%) had a preexisting chronic minor depression of at least 2 years' duration. The chronic minor depression reduced the apparent effect of the known predictors of recovery and relapse from the major depressive disorder and predicted a very pernicious course for the chronic depression. Furthermore, the longer the patient continued to suffer from a chronic minor depression after recovering from the major depression, the greater the probability that relapse into another major depression would preempt recovery from the chronic depression.

We found significant differences in time to recovery and rates of chronicity in 155 patients with bipolar illness when the episodes were subtyped into those with manic symptoms alone (pure manic), depressive symptoms alone (pure depressed), or symptoms of depression and mania (mixed or cycling) up to the time of entry into a clinical research study. Most of the patients in all three groups who did not recover received levels of somatotherapy that were generally consistent with current recommendations for intensity of treatment appropriate to each condition. Based on a median follow-up of 18 months, the life-table estimate of the probability of remaining ill for at least one year was 7% for the pure manic patients compared with 32% in patients who entered the study with episodes that were mixed or cycling. Purely depressed patients had a 22% probability of remaining ill, approximating rates found in patients without bipolar illness who have episodes of depression. Different clinical variables were found to predict time to recovery in each of these groups. We propose that this subtyping of episodes may be a clinically useful part of the classification of bipolar disorders.

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.

High levels of agreement are reported for retrospective assessment of treatment history using the Longitudinal Interval Followup Evaluation Baseline (LIFE Base), a recently developed structured psychiatric interview, in a sample of 47 subjects with a moderate to severe affective disorder. In a paired rater/observer design with interviews conducted at five different research centers, most coefficients of reliability (Kappa) were above 0.91. This is the first published reliability study of treatment data and should be encouraging to practitioners and researchers. Future research aimed at assessing the validity of treatment information obtained from patient records and clinical interviews is recommended.

In studying the risk of affective disorder in children, the investigator must deal with the problem that there are two possible units of analysis: the child and the family. An analysis based on children must take account of the intercorrelation within a sibship to produce correct results, while a family-based analysis makes it difficult to investigate individual characteristics of children that help determine the net risk. A two-stage iterative approach to this problem is proposed, yielding estimates of the effect of family-based factors (parental illness, family social class, marital status of parents) and individual factors (age and sex of child, previous non-affective illness). This technique is applied to a sample of 275 children from 143 families representing a wide range of familial risk for affective disorder. The final family-based model (predicting at least one child with affective disorder in the sibship) indicates a six-fold increase in risk to the child associated with maternal affective disorder (P less than 0.001), a three-fold increase in risk associated with paternal affective disorder (P less than 0.05) and divorce or separation of the biological parents, and a suggestion of increased risk in the highest social class (P = 0.06). The excess sibship risk, due to child factors age, prior anxiety disorder, and prior childhood diagnosis, contributed significantly to the family prediction (P less than 0.001).

Seventy recovered female nonbipolar depressed patients and 32 recovered males were individually matched for age, sex and marital status with never mentally ill control subjects. Difference scores on personality scales indicative of interpersonal dependency, learned helplessness, and other features were compared for female patients and their matched controls, vs male patients and their controls. The difference between patients and controls was not less for females than for males. Thus the hypothesis that the higher prevalence of depression in women is due to the fact that their general personality features resemble those associated with a predisposition to depression was not supported.

The clinical course of 289 patients with primary non-bipolar major depression without concurrent alcoholism was compared with that of 79 patients with non-bipolar major depression with concurrent alcoholism. Neither patient group suffered from dysthymia or current drug abuse. Contrary to expectations, the two groups did not differ on time to recovery from the major depression, time to relapse into a subsequent major depression, or various cross-sectional clinical ratings at 2 years. The two groups did differ on psychosocial status. Although they were equally impaired at index, the alcoholism group maintained significantly lower levels of psychosocial functioning throughout the 2-year follow-up period. Interpersonal relation with spouse was particularly worse among the alcoholic group.

In recent years, lower serum levels have been recommended for maintenance therapy with lithium. We studied 94 patients with bipolar disorder in a randomized, double-blind, prospective trial of two different doses of lithium for maintenance therapy: the "standard" dose, adjusted to achieve a serum lithium concentration of 0.8 to 1.0 mmol per liter, and a "low" dose, resulting in a serum concentration of 0.4 to 0.6 mmol per liter. The group medians of the patients' average serum lithium levels were 0.83 mmol per liter for the patients in the standard-range group and 0.54 mmol per liter for those in the low-range group. Six of 47 patients (13 percent) assigned to receive lithium doses that would produce serum levels in the standard range had relapses while on protocol, as compared with 18 of 47 (38 percent) assigned to the low-dose range. The risk of relapse was 2.6 times higher (95 percent confidence interval, 1.3 to 5.2) among patients in the low-range group than among those in the standard-range group. Side effects, including tremor, diarrhea, urinary frequency, weight gain, and a metallic taste in the mouth, were more frequent in the standard-range group. We conclude that doses resulting in serum lithium levels from 0.8 to 1.0 mmol per liter are more effective in treating bipolar disorder than those that result in lower serum lithium concentrations, although the higher doses are associated with a higher incidence of side effects. Recent findings about the limited nephrotoxicity of lithium, along with our observations, suggest that physicians should attempt to maintain serum lithium levels between 0.8 and 1.0 mmol per liter in most patients with bipolar disorder and that they should attempt to enhance patients' understanding of and compliance with this regimen.

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.

Results from 121 patients with major depressive disorder followed-up at 6 months with a new comprehensive follow-up schedule, the Longitudinal Interval Follow-Up Evaluation (LIFE) indicate that: (1) Forty percent of patients had not recovered from the index episode 6 months after inclusion; (2) Of those patients who recovered, 19% relapsed into another RDC affective episode by the time of the 6-month follow-up, and an additional 24% developed some subsequent affective symptoms by that time; (3) Index episodes were relatively long, with a median duration of 25 weeks from onset to recovery for recovered patients, and 67 weeks from onset to follow-up for nonrecovered patients. (4) Duration of the index episode episode prior to entry is a statistically significant predictor of short-term outcome at 6 months, as increasing durations are associated with lower rates of recovery.

Forty follow-up studies of anorexia nervosa and bulimia nervosa are reviewed. Data on recovery, relapse, and crossover are presented in addition to data on mortality, weight, eating behavior, menses, psychological functioning, and psychosexual functioning. Predictors of these outcomes are discussed. Guidelines for future research are suggested to decrease the variability that is created by differences in research methodologies and study designs.

The authors, as part of the ongoing NIMH Collaborative Study on the Psychobiology of Depression, used an analysis of variance design and videotaped interviews to explore the effects of sources of variance on the reliability of the measures being used by the NIMH study. In spite of substantial differences among interviewers in background or orientation, the authors found that diagnoses and symptom ratings were made with a high level of reliability. These results suggest that the use of structured interviews and diagnostic criteria, when combined with a careful and systematic training program, can lead to good levels of diagnostic reliability.

No statistically significant associations were found between ABO blood group distributions and RDC subtype diagnoses in 79 subjects with unipolar (single episode and recurrent) and bipolar major depressive disorder using data from our sample. We discuss methodological issues related to the control samples and choice of statistical methods in the reported studies which have looked for associations between ABO blood types and patients diagnosed as having an affective disorder. After presenting our rationale for employing the logarithm of the cross product ratio (lambda) in place of the more traditionally utilized chi-squared, we used lambda to reanalyze the original data from nine studies in the literature. The individual studies are equivocal on the basic issue of an association between type O blood and bipolar I illness, either compared to controls or to recurrent unipolar patients. The combined (weighted average) measure of association indicates a small but definite association, but statistical analysis of the dispersion of the individual estimates around this combined estimate reveals that the studies have a higher degree of heterogeneity in results than expected by chance. The consequences of this finding are discussed, and possible explanations are offered.

One hundred adolescent substance users were interviewed in a youth drop-in counseling center. The results indicated that 16% of the sample suffered from a nontransitory type of depression with a duration of at least one year with a superimposed major depressive disorder. The group with such double-depression was found to include significantly more alcohol dependent individuals as well as amphetamine abusers. The study gives further support to the DSM-III notion that depression is associated with substance use in adolescents.

The stability of the endogenous subtype of major depressive disorder was examined within individuals across consecutive episodes. The subjects were 119 probands from the NIMH Collaborative Depression Study who experienced at least two episodes of unipolar major depressive disorder within a two-year period of biannual evaluations. Structured data collection methods and Research Diagnostic Criteria were employed. The inter-episode stability of subtype diagnosis was low, never producing a kappa of greater than 0.25. This result was not attributable to threshold for diagnosis, time between episodes, differences in severity, or changes in raters.

Using survival methods the authors review and reanalyze nine published reports on relapse after recovery from depression. Despite wide disagreement over cross-sectional rates of relapse, the reanalysis reveals a common finding that the hazard of relapse declines steadily for the first three years after recovery. Methodological and design issues are discussed and summarized for the 40 naturalistic studies that report on longitudinal outcome after recovery from depression. The principles and techniques of survival methods are briefly introduced in an Appendix.

In a test-retest reliability study involving 25 psychiatric patients and 5 professional raters we demonstrate that research clinicians from collaborating institutions are able to achieve good reliability for most areas of the SADS and RDC when assessing psychiatrically ill patients under interview conditions that provide even less data than ideally obtained in the practice of clinical research. We expect greater reliability in the actual use of the SADS/RDC on most items and diagnoses since the SADS is intended to be used in conjunction with information obtained from relatives, friends, and treatment staff to confirm and clarify the judgements made by the raters on the patient interviews. Moreover, we are reassured that the diagnosis of schizo-affective disorders and schizophrenia is protected from the item unreliability found with specific delusions and hallucinations. Similarly, the difficulties in determining the episodic and chronic nature of the present episode does not substantially interfere with making an RDC diagnosis of the current condition. A complex diagnostic interview system such as the SADS and RDC requires multiple complementary techniques to determine reliability. We find that establishing explicit procedures for raters to discuss and categorize the reasons for their disagreements on individual items and diagnoses provides valuable data for understanding reliability problems. This has helped us to identify specific areas of the interview and criteria that require further clarification and more intensive rater training to improve ratings made by interviewers.

With the use of life tables to describe time while patients were well and subsequent rates of relapse for 75 patients after their recovery from an episodes of major depressive disorder in naturalistic study, a high risk of relapse was detected shortly after recovery. Twenty-four percent of patients relapsed within 12 weeks at risk, and 12% of patients relapsed with four weeks at risk. The presence of an underlying chronic depression and three or more previous affective episodes predicted a statistically significant increase in the rate of relapse. These data were used to develop an exponential model of relapse probability for a subgroup of the study population.

This article reports on a naturalistic study of the course of illness of 38 children diagnosed as having a current or past episode of major depression out of a sample of 275 children who were selected by a method not related to their psychopathology or treatment-seeking behavior. Assessments of the presence of depression and the course of this disorder were made using structured clinical interviews (DICA and DICA-P) and a criterion-based diagnostic system (DSM-III). Longitudinal methods of data analysis included the use of life tables. The proportion of children depressed for 2 years closely resembles the results found in investigations of children who sought treatment for a psychiatric disorder. The probability of remaining depressed in these children was 21% at 1 year after onset, and 10% at the 2-year point. This parallels the rate of chronicity and the decline in rates of recovery which occur over time in adult depression.

The authors present a 1-year prospective, naturalistic, longitudinal follow-up of 101 patients with the Research Diagnostic Criteria diagnosis of definite major depressive disorder. Seventy-four per cent of patients recover by 1 year. Of those who do recover, 36 per cent have subsequent Research Diagnostic Criteria affective episodes within the year. Episodes are of long duration for both the recovered and nonrecovered patients, being 30 weeks and at least 99 weeks, respectively. Certain commonly accepted ideas about the effects of age, sex, and marital status on the course and outcome of depression are not confirmed. It is demonstrated that factors which predict recovery and relapse must be differentiated. Duration of illness predict recovery but not future relapse, whereas number of previous episodes does not predict recovery but does predict future relapse.

The Longitudinal Interval Follow-up Evaluation (LIFE) is an integrated system for assessing the longitudinal course of psychiatric disorders. It consists of a semistructured interview, an Instruction booklet, a coding sheet, and a set of training materials. An interviewer uses the LIFE to collect detailed psychosocial, psychopathologic, and treatment information for a six-month follow-up interval. The weekly psychopathology measures ("psychiatric status ratings") are ordinal symptom-based scales with categories defined to match the levels of symptoms used in the Research Diagnostic Criteria. The ratings provide a separate, concurrent record of the course of each disorder initially diagnosed in patients or developing during the follow-up. Any DSM-III or Research Diagnostic Criteria disorder can be rated with the LIFE, and any length or number of follow-up intervals can be accommodated. The psychosocial and treatment information is recorded so that these data can be linked temporally to the psychiatric status ratings.