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J. Megginson Hollister, PhD; Peter Laing, PhD; Sarnoff A. Mednick, PhD, DrMed

Arch Gen Psychiatry. 1996;53(1):19-24.

Abstract
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.

Author Affiliations
From the University of Pennsylvania, Philadelphia (Dr Hollister); the Social Science Research Institute, University of Southern California, Los Angeles (Drs Hollister and mednick); Department of Immunology, University Hospital, Queens Medical Centre, Nottingham (England) University (Dr Laing); and the Institute of Preventive Medicine, Copenhagen, Denmark (Dr Mednick).

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