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Published Online: 1 September 2014

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., and Alan S. Brown, M.D., M.P.H.Authors Info & Affiliations
Publication: American Journal of Psychiatry
Volume 171, Number 9
https://doi.org/10.1176/appi.ajp.2014.13121579
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Abstract

Maternal inflammation level during pregnancy was related to risk of schizophrenia in offspring, adding new evidence for the association of infection and immune activation with the development of the disorder.

Abstract

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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Information & Authors

Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Volume 171 • Number 9 • September 2014
Pages: 960 - 968
PubMed: 24969261

History

Received: 3 December 2013
Revision received: 28 March 2014
Accepted: 11 April 2014
Published online: 1 September 2014
Published in print: September 2014

Authors

Details

Sarah Canetta, Ph.D.
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.
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Andre Sourander, M.D.
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.
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Heljä-Marja Surcel, Ph.D.
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.
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Susanna Hinkka-Yli-Salomäki, Ph.Lic.
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.
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Jaana Leiviskä, Ph.D.
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.
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Christoph Kellendonk, Ph.D.
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.
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Ian W. McKeague, Ph.D.
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.
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Alan S. Brown, M.D., M.P.H.
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.
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Notes

Address correspondence to Dr. Brown ([email protected]).

Funding Information

National Institute of Mental Health10.13039/100000025: T32 MH16434-31
National institute of Health and Medical Research10.13039/501100001677: R01 MH082052-05
: K02 MH065422-09
Dr. Kellendonk has received research support from Forest. All other authors report no financial relationships with commercial interests.Supported by grants R01 MH-082052-05 and K02 MH-065422-09 (to Dr. Brown) from NIMH and the State Research Institute and grant T32 MH-16434-31 (to Dr. Canetta) from NIMH and the Sackler Institute Fellowship.

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