Bipolar disorder (BP) and schizophrenia (SCZ) are both highly heritable (h2 ~ 0.8), often debilitating psychiatric illnesses that together affect ~2-3% of the adult population worldwide (1, 2). The distinction between BP and SCZ on the basis of clinical features, etiology, family history, and treatment response has been one of the most fundamental and controversial issues in modern psychiatric nosology. While contemporary diagnostic systems distinguish them on the basis of clinical symptomatology, duration, and associated disability, the distinction between Manic-Depressive Illness and Dementia Praecox was originally made largely on the basis of the course of illness in the late 19th century by Emil Kraepelin, who recognized that mood and psychotic symptoms could occur in both disorders (3). But clinical symptoms may not map directly onto underlying molecular mechanisms of disease. For many years, the etiological independence of these two disorders was widely accepted although transitional forms – first labeled schizoaffective disorder by Kasanin in 1933 (4) – were widely recognized. Important support for the Kraepelinian dichotomy was provided from family studies over the last 40 years that suggested at most modest familial co-aggregation of the two disorders (5-7).
