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Neurosci Biobehav Rev. 2010 May;34(6):897-921. doi: 10.1016/j.neubiorev.2009.11.022. Epub 2009 Nov 30.

Genetics and intermediate phenotypes of the schizophrenia--bipolar disorder boundary.

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Department of Psychiatry, UT Southwestern Medical Center, Dallas, TX 75235, USA.


Categorization of psychotic illnesses into schizophrenic and affective psychoses remains an ongoing controversy. Although Kraepelinian subtyping of psychosis was historically beneficial, modern genetic and neurophysiological studies do not support dichotomous conceptualization of psychosis. Evidence suggests that schizophrenia and bipolar disorder rather present a clinical continuum with partially overlapping symptom dimensions, neurophysiology, genetics and treatment responses. Recent large scale genetic studies have produced inconsistent findings and exposed an urgent need for re-thinking phenomenology-based approach in psychiatric research. Epidemiological, linkage and molecular genetic studies, as well as studies in intermediate phenotypes (neurocognitive, neurophysiological and anatomical imaging) in schizophrenia and bipolar disorders are reviewed in order to support a dimensional conceptualization of psychosis. Overlapping and unique genetic and intermediate phenotypic signatures of the two psychoses are comprehensively recapitulated. Alternative strategies which may be implicated into genetic research are discussed.

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