Elsevier

Biological Psychiatry

Volume 38, Issue 12, 15 December 1995, Pages 808-813
Biological Psychiatry

Original article
Genetic heterogeneity may in part explain sex differences in the familial risk for schizophrenia

https://doi.org/10.1016/0006-3223(95)00054-2Get rights and content

The purpose of this study was to attempt, in part, to explain significant sex differences in the familial risk (FMR) for schizophrenia found in previous studies. We hypothesized that, like probands, relatives of male vs. female probands may express different forms or subsyndromal symptoms of schizophrenia, i.e., differential expression of flat affect. Studied were 332 schizophrenic probands defined by Diagnostic and Statistical Manual of Mental Disorders, 3rd ed. (DSM-III), criteria and 725 first-degree relatives from well-known retrospective cohort family studies. Results showed that relatives of male probands were at significantly higher risk for expressing flat affect than relatives of female probands, which did not hold for relatives of normal controls. Logistic regression was used to show that when flat affect was incorporated into the definition of affected among relatives, sex differences in FMR disappeared.

References (27)

  • CrowTJ et al.

    An examination of linkage of schizophrenia and schizoaffective disorder to the pseudoautosomal region (Xp22.3)

    Br J Psychiatry

    (1994)
  • DeLisiLE et al.

    Search for linkage to schizophrenia on the X and Y chromosomes

    Am J Med Genet (Neuropsych Genet)

    (1994)
  • GoldsteinJM et al.

    Sex differences in the familial transmission of schizophrenia

    Br J Psychiatry

    (1990)
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    This study was supported, in part, by an NIMH grant MH42604 to JMG and MTT, and, in part, by an NIMH Scientist Development Award (K21 MH00976) to JMG.

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