Meta-analytic Evidence for Familial Coaggregation of Schizophrenia and Bipolar Disorder

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Several data sources suggest a link between schizophrenia and bipolar disorder (BD); however, family studies have not revealed coaggregation of these disorders. To systematically review family studies of probands with schizophrenia and BD and to determine whether these disorders coaggregate in families. MEDLINE and PsycINFO databases. All family studies published from January 1, 1980, to December 31, 2006, reporting morbid risk or raw counts of schizophrenia or BD in first-degree relatives (FDRs) of a proband group with DSM-III or later; International Classification of Diseases, Ninth or Tenth Revision; or research diagnostic criteria schizophrenia or BD were included. Of the original 2326 studies identified through the database search, 38 studies were used to investigate rates of BD in FDRs of probands with schizophrenia, while 39 studies were used to examine rates of schizophrenia in FDRs of BD probands. Data were analyzed with a novel random-effects bootstrapping technique that allows for the inclusion of studies lacking a patient or control group, which made up a substantial portion of the available data. Data were also blindly weighted for methodological quality. The FDRs of probands with schizophrenia showed significantly (P = .01) increased rates of BD relative to control FDRs (odds ratio [OR] = 2.08). The FDRs of probands with BD showed marginally (P = .06) increased rates of schizophrenia relative to control FDRs (OR = 2.10); this analysis was significant (P = .02) when studies that did not report morbid risk estimates were excluded (in this case, OR = 3.49). This meta-analysis provides direct evidence for familial coaggregation of schizophrenia and BD, a finding that argues against the view that these disorders are entirely discrete diagnostic entities. Rather, a continuum model is supported.