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Jared X. Van Snellenberg, MA, MPhil; Teresa de Candia, BA

Arch Gen Psychiatry. 2009;66(7):748-755.

Context  Several data sources suggest a link between schizophrenia and bipolar disorder (BD); however, family studies have not revealed coaggregation of these disorders.

Objectives  To systematically review family studies of probands with schizophrenia and BD and to determine whether these disorders coaggregate in families.

Data Sources  MEDLINE and PsycINFO databases.

Study Selection  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 Extraction  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.

Data Synthesis  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).

Conclusions  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.

Author Affiliations: Department of Psychology, Columbia University, New York, New York (Mr Van Snellenberg); and University of Colorado at Boulder, Boulder (Ms de Candia).

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