Dataset Information

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

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

SUBMITTER: Goldstein JM

PROVIDER: S-EPMC4477534 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Publications

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

Goldstein J M JM Cherkerzian S S Seidman L J LJ Donatelli J-A L JA Remington A G AG Tsuang M T MT Hornig M M Buka S L SL

Psychological medicine 20140326 15

<h4>Background</h4>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.<h4>Method</h4>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 ...[more]

PMID: 25065485

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Project description:BackgroundThere is a high and growing prevalence of childhood obesity which increases the risk of adult obesity and adverse physical and mental health outcomes in adulthood. Experimental and clinical data suggest that the early life environment, particularly prenatal stress, may program development of obesity in the offspring. But few studies have assessed the associations between prenatal maternal stress and rapid (ascending) weight gain, which is the strongest predictor of adult obesity and metabolic disease. Experimental data indicate that the associations may be sex dependent, but the sex-dependent association between prenatal stress and growth in the human offspring during childhood and adolescence is largely unexplored. The aim of this study is to investigate the association between prenatal exposure to stressful life events and childhood obesity in the offspring and whether maternal smoking during pregnancy and breastfeeding mediate this.MethodParticipants from a large prospective population-based Australian pregnancy cohort study (The Raine Study, n=2868) were closely and frequently followed from prenatal life (18 weeks gestation) through to adolescence. Maternal stressful life events were prospectively recorded at 18 and 34 weeks and childhood BMI (categorized into six z-score trajectories) was measured from 3 to age 14 years. We studied the prospective association between maternal exposure to stressful life events and BMI z-score trajectories in 2056 offspring (1082 boys). Mothers prospectively reported stressful life events at 18- and 34-weeks' gestation using a standardized and validated 10-point questionnaire. Age- and gender-specific z-scores for BMI were obtained from height and weight at age 3, 5, 8, 10 and 14 years using standardized methods. Latent class group analysis identified six distinct trajectory classes of BMI z-score. Multinomial logistic regression was used to examine the associations between maternal stressful life events and gender-specific BMI z-score trajectories as well as risk of overweight/obesity at each age point. Mediation analyses were also conducted to model the indirect associations through maternal smoking during pregnancy and breastfeeding.ResultsOf the 2056-included offspring, 1322 (64.3%) were exposed to at least one maternal stressful life event during early gestation and 1203 (58.5%) were exposed in late gestation. In boys, exposure to stressful life events in early but not late gestation was significantly associated with ascending (accelerated) weight-gain (ages 3-14 years) (adjusted odds ratio (aOR): 1.25, 95% CI: 1.02, 1.52) and increased risk of overweight (aOR: 1.18, 95% CI: 1.00, 1.39) aged 10 years. No similar associations were observed in girls. We observed that 29.2% of the association between more maternal stressful life events and obesity in male offspring was mediated by breastfeeding for less than 6 months. Likewise, up to 35% of the association between more maternal stressful life events and obesity in male offspring was mediated by maternal smoking during the index pregnancy.ConclusionPrenatal stress in early gestation is directly associated with accelerated childhood weight gain (assessed by childhood BMI z-score trajectories) and risk of obesity in adolescent boys, but not girls and breastfeeding and maternal smoking significantly mediates this association.

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Dataset Information

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

Background

Method

Results

Publications

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

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