German psychiatrist Emil Kraepelin (1856-1926) was one of the first to make a prominent distinction between dementia praecox (roughly corresponding to schizophrenia) with its “irreversible dementing cortical disturbances” and manic-depressive insanity (roughly corresponding to bipolar disorder, especially with psychosis), from which patients “recover with their personality intact.”(p28) Toward the end of his career, Kraepelin acknowledged that “there is an alarmingly large number of cases in which it seems impossible, in spite of the most careful observation, to make a firm diagnosis.”(p28) Indeed, most patients with psychotic disorders show complex clinical presentations not conforming to classic descriptions of either disorder. Since Kraepelin’s time, there has been great interest in identifying features that distinguish schizophrenia from bipolar disorder because prognosis and treatment approaches differ between the two. To date, the results have been mixed at best. It appears that these disease categories are not completely distinct, although boundaries between them can occasionally be detected using clinical and biological measures (eg, as described by Kotov et al and Grozeva et al).