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Rhesus Incompatibility as a Risk Factor for Schizophrenia in Male Adults

J. Megginson Hollister, PhD; Peter Laing, PhD; Sarnoff A. Mednick, PhD, DrMed
Arch Gen Psychiatry. 1996;53(1):19-24. doi:10.1001/archpsyc.1996.01830010021004.
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Background:  Rhesus (Rh) incompatibility is a cause of hemolytic disease of the fetus and newborn. Hemolytic disease results from the transplacentally transmitted maternal antibodies against Rh factor D and can cause permanent neurological damage in the affected newborn. This study examines the hypothesis that Rh incompatibility may be a risk factor for schizophrenia.

Methods:  A sample of 1867 male subjects was divided into two groups, 535 Rh incompatible and 1332 Rh compatible, and compared on rate of schizophrenia.

Results:  The rate of schizophrenia was significantly higher in the Rh-incompatible group (2.1%) compared with the Rh-compatible group (0.8%) (P<.03). In addition, since the risk for Rh hemolytic disease increases with second and later Rh incompatible pregnancies, it is noteworthy that the secondand later-born incompatible offspring exhibited a significantly higher rate of schizophrenia than secondand later-born compatible offspring (P<.05). Also, as predicted, the rate of schizophrenia among firstborn incompatible subjects was not significantly different from that of firstborn compatible subjects (1.1% vs 0.7%).

Conclusion:  Rh incompatibility may be a risk factor for schizophrenia.

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