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Elevated Maternal C-Reactive Protein and Increased Risk of Schizophrenia in a National Birth Cohort
Sarah Canetta, Ph.D.; Andre Sourander, M.D.; Heljä-Marja Surcel, Ph.D.; Susanna Hinkka-Yli-Salomäki, Ph.Lic.; Jaana Leiviskä, Ph.D.; Christoph Kellendonk, Ph.D.; Ian W. McKeague, Ph.D.; Alan S. Brown, M.D., M.P.H.
Am J Psychiatry 2014;:. doi:10.1176/appi.ajp.2014.13121579
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From the Departments of Psychiatry and Pharmacology, Columbia University Medical Center, New York State Psychiatric Institute, New York; the Department of Child Psychiatry, Faculty of Medicine, University of Turku, Turku, Finland; the Department of Child Psychiatry, Turku University Hospital, Turku, Finland; the National Institute for Health and Welfare, Oulu, Finland; the Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland; and the Departments of Biostatistics and Epidemiology, Columbia University Mailman School of Public Health, New York.

Address correspondence to Dr. Brown (asb11@columbia.edu).

Copyright © 2014 by the American Psychiatric Association

Received December 3, 2013; Revised March 28, 2014; Accepted April 11, 2014.

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Objective  The objective of the present study was to investigate an association between early gestational C-reactive protein, an established inflammatory biomarker, prospectively assayed in maternal sera, and schizophrenia in a large, national birth cohort with an extensive serum biobank.

Method  A nested case-control design from the Finnish Prenatal Study of Schizophrenia cohort was utilized. A total of 777 schizophrenia cases (schizophrenia, N=630; schizoaffective disorder, N=147) with maternal sera available for C-reactive protein testing were identified and matched to 777 control subjects in the analysis. Maternal C-reactive protein levels were assessed using a latex immunoassay from archived maternal serum specimens.

Results  Increasing maternal C-reactive protein levels, classified as a continuous variable, were significantly associated with schizophrenia in offspring (adjusted odds ratio=1.31, 95% confidence interval=1.10–1.56). This finding remained significant after adjusting for potential confounders, including maternal and parental history of psychiatric disorders, twin/singleton birth, urbanicity, province of birth, and maternal socioeconomic status.

Conclusions  This finding provides the most robust evidence to date that maternal inflammation may play a significant role in schizophrenia, with possible implications for identifying preventive strategies and pathogenic mechanisms in schizophrenia and other neurodevelopmental disorders.

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