Major depression and panic disorder: a family study perspective.
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Biomedical subjects
Publications and source records attributed to B A Prusoff.
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A family study of psychiatric disorders in 2,003 first-degree relatives of 335 probands found increased rates of bipolar I disorder and major depression (MD) in the relatives of probands with bipolar disorder and increased rates of MD in the relatives of probands with MD. There was a similarity in rates of affective disorders in the relatives of ambulatory and of hospitalized depressed probands (suggesting that ambulatory depressed patients may be as suitable as hospitalized ones for biological studies) and a comparability of rates of illness in relatives between centers for most disorders when comparable diagnostic criteria and procedures were used.
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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.
A post hoc analysis of the relationship between depression in first-degree family members (N = 810) and specific patterns of "endogenous" symptoms in 133 probands with nonbipolar major depression revealed that concomitant appetite disturbance and excessive guilt in the depressed probands was associated with increased rates of major depression among family members. The depressed, interviewed relatives of depressed probands with appetite disturbance and excessive guilt were found to be at a 2.5 greater risk for this same subtype compared with the depressed, interviewed relatives of the remaining depressed probands. These findings suggest that this subtype of depression may "breed true" within these families.
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.
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.
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In a family study of major depression, the prevalence of bipolar illness was nearly six times as high among the relatives of delusionally depressed probands as among the relatives of nondelusionally depressed probands or of controls.
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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.
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.
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.
The authors report data from a case-control family study of lifetime psychiatric diagnoses among the relatives of individuals with major depression. Specifically, they address the relationship between anxiety disorders and major depression. The findings indicate that relatives of individuals with major depression plus an anxiety disorder are at greater risk for major depression, as well as anxiety disorders; than are the relatives of individuals with major depression without an anxiety disorder. This increased risk appears to be present whether or not the anxiety disorder occurs solely in association with episodes of major depression or is temporally separate. The nosological implications of these findings are discussed.
Interpersonal psychotherapy (IPT), a short-term treatment developed and tested for use with ambulatory depressed patients, has been successfully applied to elderly patients in a recent pilot study. Case reports of treated elderly patients are presented and the specific utility of IPT for this population is described. The potential of short-term psychotherapies for the treatment of the elderly is discussed and research directions are outlined.
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.
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.
This study compares information on the diagnosis of depression obtained by family history reports with the formation obtained by direct interview. Reports were obtained from family members on the psychiatric status of 696 individuals for whom direct SADS-L interviews were also available. The effects on family history reports of subjects characteristics, treatment status, age of onset of depression, and endogenous symptoms were examined. Sensitivity and specificity for family history reports on the specific symptoms of depression are also reported. The specificity of family history reports for the diagnosis of depression was consistently high but sensitivity varied as a function of subject and illness characteristics. Sensitivity was somewhat higher for females than males and appreciably higher for probands than for their first-degree relatives and spouses. Sensitivity was increased whenever treatment, hospitalization or endogenous symptoms were present in the subject, indicating that family history reports are most accurate for detecting the severest cases of depression. Finally, the symptoms of depression that are least accurately reported by relatives are identified and suggestions for modifying the family history criteria for depression are proposed.