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Published Online: 1 March 2010

Prenatal Infection and Schizophrenia: A Review of Epidemiologic and Translational Studies

Abstract

Abstract

An emerging literature from epidemiologic, clinical, and preclinical investigations has provided evidence that gestational exposure to infection contributes to the etiology of schizophrenia. In recent years, these studies have moved from ecologic designs, which ascertain infection based on epidemics in populations, to investigations that have capitalized on reliable biomarkers in individual pregnancies. These studies have documented specific candidate infections that appear to be associated with an elevated risk of schizophrenia. Animal models of maternal immune activation inspired by this work have revealed intriguing findings indicating behavioral, neurochemical, and neurophysiologic abnormalities consistent with observations in schizophrenia. In parallel studies in humans and animals, investigators are working to uncover the cellular and molecular mechanisms by which in utero exposure to infection contributes to schizophrenia risk. In this review, the authors discuss and critically evaluate the epidemiologic literature on in utero exposure to infection and schizophrenia, summarize emerging animal models of maternal immune activation, and discuss putative unique and common mechanisms by which in utero exposure to infection alters neurodevelopment, potentially increasing susceptibility to schizophrenia. The promise of this work for facilitating the identification of susceptibility loci in genetic studies of schizophrenia is illustrated by examples of interaction between in utero exposure to infection and genetic variants. The authors then elaborate on possible implications of this work, including the use of preventive measures for reducing the incidence of schizophrenia. Finally, they discuss new approaches aimed at addressing current challenges in this area of research.

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Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Pages: 261 - 280
PubMed: 20123911

History

Received: 12 March 2009
Accepted: 5 October 2009
Published online: 1 March 2010
Published in print: March 2010

Authors

Details

Alan S. Brown, M.D., M.P.H.
Elena J. Derkits, B.A.

Notes

Received March 12, 2009; revisions received Sept. 9 and Sept. 28, 2009; accepted Oct. 5, 2009. From New York State Psychiatric Institute, Columbia University College of Physicians and Surgeons, and Mailman School of Public Health of Columbia University. Address correspondence and reprint requests to Dr. Brown, New York State Psychiatric Institute, 1051 Riverside Dr., Unit 23, New York, NY 10032; [email protected] (e-mail).

Competing Interests

The authors report no financial relationships with commercial interests.

Funding Information

Supported by NIMH grants 1R01MH-60249, 1R01MH-082052-01A1, and 1K02-MH65422 to Dr. Brown, a NARSAD Independent Investigator Award to Dr. Brown, and National Institute on Child Health and Development grants N01-HD-1-3334 and N010HD-6-3258 to B.A. Cohn.

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