The Kraepelinian Dichotomy From the Perspective of Prenatal Infectious and Immunologic Insults

The "Kraepelinian dichotomy" between schizophrenia (SZ) and bipolar disorder (BD) has been a dominant force in our thinking on the classification of these mental disorders. Emerging evidence indicates that these 2 disorders overlap significantly with regard to epidemiology, clinical presentation, genetic susceptibility, structural neuroanatomy, and treatment. Prenatal infection and immunologic dysfunction appear to be risk factors for both SZ and BD; some of these gestational exposures are present in both disorders while others may be specific to 1 or the other of the 2 syndromes. In this paper, we shall review prior studies of prenatal infections and immunologic insults in schizophrenia and BD, including exposures which overlap and which differ between these disorders, discuss the potential utility of maternal infection as one strategy toward developing a more biologically meaningful diagnostic classification system, and propose new recommendations for future research aimed at dissecting these 2 disorders from one another at the etiologic level.