Etiologic, phenomenologic, and endophenotypic overlap of schizophrenia and bipolar disorder.

This review examines the history of psychiatric nosology, with particular reference to the nineteenth-century origins of the concepts of manic-depressive illness and schizophrenia as distinct clinical syndromes and their evolution and diagnostic refinement over time. I document how the terminology applied to these entities has generated controversy, and discuss the ways in which the resulting diagnostic entities as defined by pure phenomenological symptom descriptors fail to capture discrete diagnostic distinctions, leading some researchers to posit an illness continuum rather than separate disorders. Furthermore, the two syndromes overlap substantially on multiple biologic measures, and clarity is lacking as to the underlying etiology and pathology necessary to move from descriptions of clinical syndromes to diseases. I next examine how biologically based classifications agnostic to conventional diagnostic schemes may be useful and how these are being implemented in practice, and conclude by summarizing where such approaches are likely to lead.