Reliability of depression and associated clinical symptoms.

Interrater reliability assessments were undertaken for the Hamilton Depression Rating Scale, the Raskin Depression Rating Scale, and the Degree of Mental Illness Scale. Levels of reliability ranged from "poor" to "excellent" and varied as a function of (1) temporality (assessments made at termination of clinical trial more reliable than those made at randomization into treatment) and (2) unit of scoring (factor or total scores more reliable than single-item assessments). The implications of these results may be considered in the context of further studies evaluating the efficacy of treatment interventions on reduction of symptoms of clinical depression.

Familial pattern of Gilles de la Tourette syndrome.

As part of a pilot questionnaire survey of Gilles de la Tourette syndrome (TS), data on TS and tics for relatives of 75 patients with TS were collected. The frequencies of TS and/or tics among relatives were significantly heterogeneous in a familial pattern that suggests (1) that the disorder is transmitted, with tics alone being a milder manifestation, and that this severity difference is a threshold phenomenon related to transmission; (2) that the sex difference in prevalence is real because it was found among relatives of both male and female probands; and (3) that the sex difference is related to transmission as a threshold effect since female probands, although less common than male probands, had a higher proportion of affected relatives. These pilot data provide evidence for the transmission of TS and can be qualitatively explained by a genetic model of transmission.

Suicide attempts and recent life events. A controlled comparison.

Life events experienced in the six months before a suicide attempt were compared with events for two matched control groups. Suicide attempters reported four times as many events as were reported by subjects from the general population and 11/2 times as many as were reported by depressed patients prior to depressive onset. A substantial peaking of events occurred in the month before the attempt. The excess over general population controls spanned most types of event. That over depressive onset was more selective, and it involved events with threatening implications, including undesirable events, those rated as stressful, and those outside the respondent's control. Unlike depression, suicide attempts were preceded equally by entrances and exits in the social field. Overall, the findings indicate a strong and immediate relationship between suicide attempts and life events.

An evaluation of the family history method for ascertaining psychiatric disorders.

This methodologic study assessed the accuracy of family history data in ascertaining psychiatric disorders in relatives. Comparison of diagnoses based on family history with diagnoses based on direct interview indicated that the specificity for the family history method is high, but that the sensitivity is generally low. Accuracy was better for affective disorders and alcoholism than for less severe disorders; spouses and offspring provided more accurate information than parents and siblings. The use of multiple information increased sensitivity somewhat, with little adverse effect on specificity. However, because errors were often correlated when more than one person provided information about a particular relative, the use of multiple informants generally did not improve accuracy substantially. Analysis of family-genetic studies should take account of the differential quality of data obtained by the family history method vs direct interview.

Variability in rates of affective disorders in relatives of depressed and normal probands.

Familial studies of depressed probands vary in the absolute rates of affective disorders in relatives. In a study of 215 mild and severely depressed nonbipolar major depressives and normal probands and 1,331 adult first-degree relatives, attempts were made to account for the sources of variance. The results demonstrated familial aggregation, although degree of aggregation of absolute rates of affective disorders varied among relatives according to the definition of depression used for the relatives, the source of data, and the composition of the relative sample. Despite this variability, the magnitude of the difference in rates between relatives of the normal persons and of the depressed probands remained constant. The rates of affective disorders were always higher in the relatives of the depressed than in the relatives of the normal probands. The magnitude of the difference in rates of depression between the relatives of the depressed subjects and the relatives of the normal probands ranged approximately between twofold and fivefold.

Differential symptom reduction by drugs and psychotherapy in acute depression.

A randomized, controlled trial compared the combination of amitriptyline hydrochloride and short-term interpersonal psychotherapy, either treatment alone, and a nonscheduled treatment control group in ambulatory acute, nonbipolar, nonpsychotic depressives. Results show the efficacy of both psychotherapy and amitriptyline in overall symptom reduction. Amitriptyline and psychotherapy were about equal, and the effects of both treatments in combination were additive. The additive effect of combined treatment was largely due to the differential effects of the two treatments. Amitriptyline had its effect mainly on the vegetative symptoms of depression such as sleep and appetite disturbance, these occurred early in treatment, often within the first week. Psychotherapy had its effect mainly on mood, suicidal ideation, work, and interests; these effects occurred slightly later, at four to eight weeks.

Familial transmission of depression and alcoholism.

The familial transmission of major depression and alcoholism among probands who had depression and alcoholism was examined. Our findings indicated that depressives without alcoholism did not transmit alcoholism, and probands with depression and alcoholism tended to transmit both depression and alcoholism. This confirms the observation that depression and alcoholism are not manifestations of the same underlying disorder. An increased risk of anxiety disorders in the relatives of probands with alcoholism, which could specifically be attributed to the presence of alcoholism in addition to an anxiety disorder in the proband, was also observed. This suggested that the alcoholism in these probands may result from self-medication of anxiety symptoms. The results of this study underscore the importance of examining combinations of diagnoses in patients in decreasing the heterogeneity of diagnostic categories.

Family-genetic studies of psychiatric disorders. Developing technologies.

During the past decade new concepts and technologies have improved the conduct of family-genetic studies in psychiatry. We compiled and critically evaluated these advances, including study design, pedigree collection, diagnostic procedures in adults and children, and epidemiologic and genetic approaches to data analysis. These approaches have improved the collection of accurate information on the nature and patterns of psychiatric illness in families. The data generated from well-designed and well-conducted family studies are useful for the identification of homogeneous subgroups of psychiatric disorders, for understanding the spectrum of psychiatric disorders, for examining the associations between psychiatric disorders, and for studying the continuity between adult and childhood manifestations of psychiatric disorders. Findings from these studies also may enhance our capacity to identify the mode of transmission of the psychiatric disorders and to select potentially informative families for future genetic linkage studies using the new recombinant DNA techniques. The adaptation of these methods to routine clinical practice and new directions in the application of family-genetic studies employing more refined assessments and analytic methods are also discussed.

Psychiatric diagnoses of treatment-seeking cocaine abusers.

In a sample of 298 cocaine abusers seeking inpatient (n = 149) or outpatient (n = 149) treatment, rates of psychiatric disorders were determined by means of the Schedule for Affective Disorders and Research Diagnostic Criteria. Overall, 55.7% met current and 73.5% met lifetime criteria for a psychiatric disorder other than a substance use disorder. In common with previous reports from clinical samples of cocaine abusers, these overall rates were largely accounted for by major depression, minor bipolar conditions (eg, hypomania, cyclothymic personality), anxiety disorders, antisocial personality, and history of childhood attention deficit disorder. Affective disorders and alcoholism usually followed the onset of drug abuse, while anxiety disorders, antisocial personality, and attention deficit disorder typically preceded drug abuse.

Panic disorder and major depression. Increased risk of depression, alcoholism, panic, and phobic disorders in families of depressed probands with panic disorder.

In a large, case-control family study of depression, 77 (58%) of 133 depressed probands displayed anxiety symptoms that met DSM-III criteria for agoraphobia, panic disorder, or generalized anxiety disorder. In two thirds of these 77 cases, these symptoms were associated with depressive episodes. In a previous study, the lifetime rate of major depression and anxiety disorders among first-degree family members of probands with major depression plus an anxiety disorder was found to be significantly increased regardless of when the anxiety symptoms occurred. In this study we analyzed our data according to the specific anxiety disorders observed. Major depression plus panic disorder in probands was associated with a marked increase in risk in relatives for a number of psychiatric disorders; relatives were more than twice as likely to have major depression, panic disorder, phobia, and/or alcoholism than the relatives of probands with major depression without any anxiety disorder. These results indicate that the relationship between major depression and anxiety disorders requires further study.

Depressed outpatients. Results one year after treatment with drugs and/or interpersonal psychotherapy.

A one-year follow-up was conducted on ambulatory nonbipolar, nonpsychotic, acutely depressed patients who received amitriptyline hydrochloride and/or interpersonal psychotherapy (IPT), each alone and in combination, as part of a four-month clinical trial. There were no differential long-term effects of the initially randomized treatment on clinical symptoms one year later since most of the patients were asymptomatic. While most patients were functioning reasonably well, there were some main effects of IPT on social functioning at the one-year follow-up. Patients who received IPT with or without pharmacotherapy were doing significantly better on some measures of social functioning.

Research diagnostic criteria subtypes of depression. Their role as predictors of differential response to psychotherapy and drug treatment.

We studied the usefulness of the research diagnostic criteria subtypes in the prediction of response to amitriptyline and short-term interpersonal psychotherapy (IPT) in a 16-week, controlled, randomized clinical trial with 81 ambulatory depressed patients. Both patients with a situational depression and patients with an endogenous depression responded to combined treatment; those with an endogenous depression did not respond to IPT alone, whereas those with a situational depression responded to IPT or tricyclic medication alone. It may not be necessary to offer both treatments to the situationally depressed patients. However, situational and endogenous are not mutally exclusive diagnoses, and it would be of clinical interest to obtain a longer group of patients with both diagnoses for further study.

Treatment of secondary depression in schizophrenia. A double-blind, placebo-controlled trial of amitriptyline added to perphenazine.

The combination of antidepressants and neuroleptics has been widely recommended and commonly used clinically for the schizophrenic patient who becomes depressed. However, the value of the combination for these patients has not been clearly demonstrated. This report presents results of a double-blind, randomized, placebo-controlled clinical trial designed to evaluate the combination of perphenazine and amitriptyline hydrochloride with that of perphenazine alone in the treatment of 35 ambulatory chronic schizophrenic patients in whom depressive symptoms developed. Results showed that the addition of amitriptyline to perphenazine, when compared with perphenazine alone, was more effective in reducing symptoms of depression after four months of treatment, but less effective in reducing thought disorder. The study concludes that the value of adding an antidepressant to the usual neuroleptic in the treatment of secondary depression in schizophrenia should be reviewed.

Depression and anxiety disorders in parents and children. Results from the Yale family study.

The children (aged 6 to 17 years) of probands with primary major depression, with and without various anxiety disorders, were compared with the children of a matched normal control group. The results from the study of these young children parallel our previous findings among the adult first-degree relatives of these probands. Depression in the proband increased the risk of depression in the children. Depression plus panic disorder or agoraphobia in the proband conferred an additional risk of depression and of an anxiety disorder in the children. Panic disorder in the parents conferred more than a threefold increased risk of separation anxiety in the children. Other factors that increased the risk to children were degree of familial loading for psychiatric illness, parental assortative mating, and parental recurrent depression. The findings suggest a relationship between depression and some of the anxiety disorders, and between adult panic disorder and agoraphobia and transmission of anxiety disorders to children.

Assessing psychiatric disorders in children. Discrepancies between mothers' and children's reports.

Results were compared from independent interviews using the Schedule for Affective Disorders and Schizophrenia for School-aged Children-Epidemiologic Version and DSM-III with 220 subjects (ages 6 to 23 years) and their parent informants. In agreement with results from studies using a variety of structured diagnostic interviews or symptom scales, considerable discrepancies were found between parents' and children's reports on the degree and nature of the child's psychopathology. The children reported more illness about themselves than their parents reported about them. The parents' reports were primarily a subset of the children's reports. Various factors that might affect agreement, including demography, parental clinical status, severity of illness, and treatment, were also explored. The findings that parents under-report psychiatric disorders in their children are comparable with those reported in studies of adults when family informants are used to obtain diagnostic information. Until these parent-child discrepancies can be resolved by longitudinal, family, and other research, diagnostic assessment of children should include direct interviews with them. An independent assessment of the child's diagnosis based on information from multiple informants, including the child, may be the best estimate.

Children of depressed parents. Increased psychopathology and early onset of major depression.

Data on the psychiatric diagnosis, overall functioning, and treatment of 220 6- to 23-year-old subjects who were at high or low risk for major depression are presented. The subjects' diagnoses were made by a child psychiatrist based on best-estimate evaluation of diagnostic information derived from structured interviews (Schedule for Affective Disorders and Schizophrenia for School-Aged Children, Epidemiologic Version) with the subjects and separately with their mothers about their children. The major findings were an increased overall prevalence of major depression and substance abuse, psychiatric treatment, poor social functioning, and school problems in the children of depressed proband parents compared with children of normal proband parents. Overall prepubertal depression was uncommon and the sex ratios were equal. After 12 years of age, there was an increasing preponderance of female subjects in the group with major depression. The mean age at onset of major depression was similar for male and female subjects. However, it was significantly earlier in the children of depressed probands (mean age at onset, 12 to 13 years) compared with the children of normal probands (mean age at onset, 16 to 17 years). Symptom profiles and additional types of diagnoses in the depressed children from either proband parent group did not differ. These children are being followed up longitudinally to determine the prognostic significance, persistence, recurrence, and recall of their symptoms. Several research and clinical strategies are suggested by these data.

Understanding the clinical heterogeneity of major depression using family data.

For major depression, putative subgroups have been defined by age at onset, clinical severity, symptom patterns, or the presence of other disorders (comorbidity), yet the high degree of overlap in clinical presentation makes it difficult to determine which combination of criteria for defining subgroups best predicts familial aggregation. In dealing with this overlap, we found that only early age at onset, or major depression with an anxiety disorder or secondary alcoholism, were independently related to increased risk of major depression in relatives. Once the effects of these proband factors had been taken into account, endogenous, delusional, melancholic, or autonomous symptom patterns, recurrent depression, history of hospitalization, and suicidal ideation or attempts in probands were not associated with increased risk of major depression in relatives.

Imipramine as treatment for depression in addicts.

This report describes the results of a placebo-controlled double-blind clinical trial evaluating imipramine hydrochloride, a tricyclic antidepressant, as treatment for depression in methadone-maintained opiate addicts. Forty-six subjects were assigned randomly to either the imipramine or placebo group for up to eight weeks. All patients also received mandatory once weekly group therapy as part of the methadone program. Outcome measures included attrition, depressive symptoms, global improvement, side effects, social functioning, and urine specimen results positive for illicit drugs. The therapeutic response in the two conditions was similar. Addicts receiving either imipramine or placebo experienced a substantial reduction of depressive symptoms during the eight weeks of the study. These findings are compared with other studies that treat depression in addicts and nonaddicts.

Subtypes of depression. Family study perspective.

To address the validity of subtype distinctions within a large family study of major depression, probands (N = 133) were classified into several non-mutually exclusive subcategories, including endogenous (n = 89), melancholic (n = 61), autonomous (n = 50), and delusional (n = 21). Age-corrected lifetime rates of depression and subtypes among first-degree relatives were then compared by the proband's depression subtype. Rates of major depression were highest for the relatives of probands with the autonomous and delusional subtypes, and while lower for the relatives of endogenous and melancholic probands, these rates were still higher than for the relatives of the remaining depressed probands or the relatives of normal controls. The depressed relatives of depressed probands with the endogenous, melancholic, autonomous, or delusional subtypes were more likely to have one of these subtypes than the depressed relatives of either the remaining depressed probands or the normal controls.

Onset of major depression in early adulthood. Increased familial loading and specificity.

In a family study of 133 probands with major depression and 82 normal control subjects, and 1,518 of their first-degree relatives, we found a substantial inverse relationship between the age of onset of major depression in the probands and the risk of major depression in their relatives. The relatives of probands whose onset of major depression occurred when they were younger than 20 years of age had the highest risk of major depression, compared with the relatives of probands who had later ages of onset or with the relatives of normal subjects. Probands with an age of onset of 40 years or more had familial loading that was only slightly higher than the families of normal control subjects. Our statistical methods enabled us to examine the relationship of the ages of onset in the probands and their relatives while accounting for possible confounding factors. More studies will be needed to sort out secular changes in the rates of the occurrence of major depression among young persons (cohort effect) from the high familial loading of major depression that has its onset in childhood and adolescence, and to determine whether the specificity of transmission of early-onset depression is the result of a single homogeneous disorder.