January 1996

Rhesus Incompatibility as a Risk Factor for Schizophrenia in Male Adults

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).

Arch Gen Psychiatry. 1996;53(1):19-24. doi:10.1001/archpsyc.1996.01830010021004

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.