Rhesus incompatibility as a risk factor for schizophrenia in male adults

Arch Gen Psychiatry. 1996 Jan;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 second- and later-born incompatible offspring exhibited a significantly higher rate of schizophrenia than second- and 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Birth Order
  • Cohort Studies
  • Comorbidity
  • Denmark / epidemiology
  • Family
  • Female
  • Humans
  • Infant, Newborn
  • Male
  • Pregnancy
  • Prevalence
  • Rh Isoimmunization / complications
  • Rh Isoimmunization / epidemiology*
  • Rh-Hr Blood-Group System / genetics
  • Risk Factors
  • Schizophrenia / epidemiology*
  • Schizophrenia / etiology
  • Schizophrenia / genetics
  • Sex Factors


  • Rh-Hr Blood-Group System