On the basis of genetic studies, previous investigators have proposed the existence of two types of affective disorder: (1) primary affective disorder, manic-depressive disease, and (2) primary affective disorder, depressive type. This is a study of the pattern of inheritance in families of probands with the depressive type disease. Data from five previously published series of patients with affective disorder were analyzed for morbid risk of affective illness in siblings and children of probands who had depressions only and in whose families no mania occurred. Significant sex differences in morbid risk were found in both siblings and children of female probands: low risks for affective disorder in brothers and sons, compared to higher risks for sisters and daughters. Morbid risks for the siblings and children of male probands showed no sex difference in morbid risk for affective disorder. This pattern of risk for depressive illness is not compatible with the genetic model proposed by Reich, Clayton and Winokur of an X-linked dominant inheritance for manic-depressive illness. This finding supports the hypothesis of two types of affective disorder. The pattern of an excess of ill daughters and sisters of female probands is difficult to explain by a simple genetic model, but is compatible with the hypothesis that depressive illness is made up of at least two subgroups: one group in which males and females inherit an equal morbid risk, and a second group in which the illness is sex-limited to females.
Bibliographical noteFunding Information:
From the Department of Psychiaty, Louis, MO. Supported in part by VSPHS Grants MH-05804, MH-05938, MH-07698 and MH-13002. REMI J. CADOFLETM, .D.: Assistant Professor of Psychiatry, Washington University School of Medicine, St. Louis, MO. GEORGE WINOKUR, M.D.: Professor of Psychiaty, Washington University School of Medicine, St. Louis, MO. PAULA J. CLAYTON, M.D.: Assistant Professor of Psychiatry, Washington University School of Medicine, St. Louis, MO.