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Prenatal maternal immune disruption and sex-dependent risk for psychoses

Published online by Cambridge University Press:  26 March 2014

J. M Goldstein ,
S. Cherkerzian ,
L. J. Seidman ,
J.-A. L. Donatelli ,
A. G. Remington ,
M. T. Tsuang ,
M. Hornig  and
S. L. Buka
J. M Goldstein*
Affiliation:
Connors Center for Women's Health and Gender Biology, Brigham and Women's Hospital, Boston, MA, USA Departments of Psychiatry and Medicine, Harvard Medical School, Boston, MA, USA Division of Psychiatric Neuroscience, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA
S. Cherkerzian
Affiliation:
Connors Center for Women's Health and Gender Biology, Brigham and Women's Hospital, Boston, MA, USA Departments of Psychiatry and Medicine, Harvard Medical School, Boston, MA, USA
L. J. Seidman
Affiliation:
Division of Psychiatric Neuroscience, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA Harvard Medical School, Department of Psychiatry, Massachusetts Mental Health Center; Division of Public Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA, USA
J.-A. L. Donatelli
Affiliation:
Department of Epidemiology, Brown University, Providence, RI, USA
A. G. Remington
Affiliation:
Connors Center for Women's Health and Gender Biology, Brigham and Women's Hospital, Boston, MA, USA
M. T. Tsuang
Affiliation:
Beth Israel Deaconess Hospital, Department of Psychiatry, Division of Public Psychiatry, Massachusetts Mental Health Center and Harvard Medical School, Boston, MA, USA Center for Behavioral Genomics, Department of Psychiatry; Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA, USA Harvard Institute of Psychiatric Epidemiology and Genetics, Harvard School of Public Heath, Boston, MA, USA
M. Hornig
Affiliation:
Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY, USA
S. L. Buka
Affiliation:
Department of Epidemiology, Brown University, Providence, RI, USA
*
*Address for correspondence: Dr J. M. Goldstein, Brigham and Women's Hospital, One Brigham Circle, Division of Women's Health, 1620 Tremont Street, 3rd Floor, Boston, MA 02120, USA. (Email: jill_goldstein@hms.harvard.edu)
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Abstract

Background.

Previous studies suggest that abnormalities in maternal immune activity during pregnancy alter the offspring's brain development and are associated with increased risk for schizophrenia (SCZ) dependent on sex.

Method.

Using a nested case–control design and prospectively collected prenatal maternal sera from which interleukin (IL)-1β, IL-8, IL-6, tumor necrosis factor (TNF)-α and IL-10 were assayed, we investigated sex-dependent associations between these cytokines and 88 psychotic cases [SCZ = 44; affective psychoses (AP) = 44] and 100 healthy controls from a pregnancy cohort followed for > 40 years. Analyses included sex-stratified non-parametric tests adjusted for multiple comparisons to screen cytokines associated with SCZ risk, followed by deviant subgroup analyses using generalized estimating equation (GEE) models.

Results.

There were higher prenatal IL-6 levels among male SCZ than male controls, and lower TNF-α levels among female SCZ than female controls. The results were supported by deviant subgroup analyses with significantly more SCZ males with high IL-6 levels (>highest quartile) compared with controls [odd ratio (OR)75 = 3.33, 95% confidence interval (CI) 1.13–9.82], and greater prevalence of low TNF-α levels (<lowest quartile) among SCZ females compared with their controls (OR25 = 6.30, 95% CI 1.20–33.04) and SCZ males. Higher levels of IL-6 were only found among SCZ compared with AP cases. Lower TNF-α levels (non-significant) also characterized female AP cases versus controls, although the prevalence of the lowest levels was higher in SCZ than AP females (70% v. 40%), with no effect in SCZ or AP males.

Conclusions.

The results underscore the importance of immunologic processes affecting fetal brain development and differential risk for psychoses depending on psychosis subtype and offspring sex.

Keywords

Fetal programminginflammationpsychosesschizophreniasex differences
Type
Original Articles
Information
Psychological Medicine , Volume 44 , Issue 15 , November 2014 , pp. 3249 - 3261
Copyright
Copyright © Cambridge University Press 2014 

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