Approaches for unraveling the joint genetic determinants of schizophrenia and bipolar disorder

Since Emil Kraepelin proposed in 1919 that dementia praecox (schizophrenia) be differentiated from manic depression (bipolar disorder), the concept of nosological dichotomy has greatly influenced the diagnosis, treatment, and research of pathogenesis of these 2 disorders. However, this concept has recently been challenged by increasing evidence showing biological overlap between schizophrenia and bipolar disorder. This article reviews some of the previous evidence for phenomenological and molecular overlaps between these 2 disorders. We then discuss approaches for examining shared etiological mechanisms with a concentration on genetic factors. We have put a particular emphasis on incorporating the concept of endophenotypes in research of shared genetic liability for these 2 disorders.