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Psychol Med. 2014 Nov;44(15):3249-61. doi: 10.1017/S0033291714000683. Epub 2014 Mar 26.

Prenatal maternal immune disruption and sex-dependent risk for psychoses.

Author information

1
Connors Center for Women's Health and Gender Biology,Brigham and Women's Hospital, Boston, MA,USA.
2
Division of Psychiatric Neuroscience,Department of Psychiatry,Massachusetts General Hospital, Boston, MA,USA.
3
Department of Epidemiology,Brown University,Providence, RI,USA.
4
Beth Israel Deaconess Hospital,Department of Psychiatry,Division of Public Psychiatry, Massachusetts Mental Health Center and Harvard Medical School, Boston, MA,USA.
5
Department of Epidemiology, Mailman School of Public Health,Columbia University,New York, NY,USA.

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.

PMID:
25065485
PMCID:
PMC4477534
DOI:
10.1017/S0033291714000683
[Indexed for MEDLINE]
Free PMC Article

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