The Etiology of Affective Illness

The introduction of effective psychopharmacological drugs four decades ago sparked a revolution that has, over time, reshaped scientific and popular concepts of mental illness. Like all revolutionary periods, the era blazed with activity, as investigators conducted studies into the neurobiological mechanisms that might explain the powerful, specific effects of the new drugs. Recurrent major affective illness - manic depressive illness in classical Kraepelin terms - quickly became the clinical mainstay for such research, a model for biological studies on other major mental illness. More homogeneous than nonrecurrent unipolar depression or schizophrenia, manic depressive illness attracted scientific attention for other reasons as well: Its genetic diathesis (reviewed by Gershon in this volume) was clear to many clinicians treating the illness; its cyclic nature - particularly the bipolar subtype - gave investigators the opportunity to study the transition phases and to separate the traits intrinsic to the illness from the state changes that accompany being ill; and finally, lithium’s effects on both poles of the bipolar subtype presented an irresistible scientific challenge.