Will the Kraepelinian Dichotomy Survive DSM-V?

Kraepelin proposed dementia praecox and manic-depressive illness as the two major psychotic disorders. This paradigm is still prevalent, but observations of overlapping boundaries between bipolar disorder and schizophrenia challenge this dichotomy. However, the concept of schizophrenia has been radically altered from the original Kraepelinian proposal. We defend the two psychoses positions, but suggest two flaws in the heuristic application: (1) overlapping features, such as psychotic symptoms, are not decisive in differential diagnosis; and (2) each disorder is a syndrome, not a disease entity. An alternative paradigm based on domains of pathology is more powerful for studies of etiology, pathophysiology, and therapeutic discovery. Neuropsychopharmacology (2009) 34, 2081-2087; doi:10.1038/npp.2009.32; published online 18 March 2009