MODE OF INHERITANCE IN FAMILIES OF PATIENTS WITH LITHIUM-RESPONSIVE AFFECTIVE-DISORDERS

A better understanding of the role of genetic factors in affective dis orders is likely to result from investigating more homogeneous populat ions. To achieve this goal, we have systematically studied patients wh o are excellent responders to long-term lithium treatment and their re latives. In the families of 71 such probands, we have analyzed the mod e of inheritance by comparing the observed morbidity risks with the ri sks expected under different genetic models. The results demonstrate m ajor-gene effects in the transmission of primary affective disorders; the polygenic model with sex-specific thresholds could be rejected. Di scrimination between the autosomal and X-chromosome models was not pos sible, but the autosomal recessive model predicts more realistic, gend er-specific frequencies of affective disorders in the general populati on. These results suggest that autosomal recessive inheritance deserve s serious consideration in molecular genetic investigations.