Multiple sclerosis and affective disorder. Family history, sex, and HLA-DR antigens.

To investigate a possible genetic cause underlying the clinical association between multiple sclerosis (MS) and affective disorder, we studied 56 patients with MS for psychiatric and genetic (family history, sex, and HLA-DR) characteristics. The 2:1 ratio of females to males expected for patients with MS was observed in this sample (40:16), but the excess of females occurred entirely among the 31 MS patients with major affective disorder (27 females and four males). Bipolar probands with MS had significantly more relatives with affective disorder or MS than did unipolar probands with MS. The HLA-DR antigen frequencies in patients with MS categorized by type and family history of affective disorder suggest that it may be possible to validate such clustering of patients. We concluded that sex and other genetic factors are related to the affective symptoms in MS and emphasize the importance of psychiatric evaluation of these patients.