Dataset Information

DNA methylation mediates the effect of maternal cognitive appraisal of a disaster in pregnancy on the child's C-peptide secretion in adolescence: Project Ice Storm.

ABSTRACT: Animal and human studies suggest that prenatal exposure to stress is associated with adverse health outcomes such as type 2 diabetes. Epigenetic modification, such as DNA methylation, is considered one possible underlying mechanism. The 1998 Quebec ice storm provides a unique opportunity to study an independent prenatal stressor on child outcomes. C-peptide is the best measure of endogenous insulin secretion and is widely used in the clinical management of patients with diabetes. The objectives of this study are to determine 1) the extent to which prenatal exposure to disaster-related stress (maternal objective hardship and maternal cognitive appraisal) influences children's C-peptide secretion, and 2) whether DNA methylation of diabetes-related genes mediates the effects of prenatal stress on C-peptide secretion. Children's (n = 30) C-peptide secretion in response to an oral glucose tolerance test were assessed in blood at 13½ years. DNA methylation levels of selected type 1 and 2 diabetes-related genes were chosen based upon the genes associated with prenatal maternal objective hardship and/or cognitive appraisal levels. Bootstrapping analyses were performed to determine the mediation effect of DNA methylation. We found that children whose mothers experienced higher objective hardship exhibited higher C-peptide secretion. Cognitive appraisal was not directly associated with C-peptide secretion. DNA methylation of diabetes-related genes had a positive mediation effect of objective hardship on C-peptide secretion: higher objective hardship predicted higher C-peptide secretion through DNA methylation. Negative mediation effects of cognitive appraisal were observed: negative cognitive appraisal predicted higher C-peptide secretion through DNA methylation. However, only one gene, LTA, remained a significant mediator of cognitive appraisal on C-peptide secretion after the conservative Bonferroni multiple corrections. Our findings suggest that DNA methylation could act as an intervening variable between prenatal stress and metabolic outcomes, highlighting the importance of epigenetic mechanisms in response to environmental factors.

SUBMITTER: Cao-Lei L

PROVIDER: S-EPMC5798828 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

DNA methylation mediates the effect of maternal cognitive appraisal of a disaster in pregnancy on the child's C-peptide secretion in adolescence: Project Ice Storm.

Cao-Lei Lei L Dancause Kelsey N KN Elgbeili Guillaume G Laplante David P DP Szyf Moshe M King Suzanne S

PloS one 20180205 2

Animal and human studies suggest that prenatal exposure to stress is associated with adverse health outcomes such as type 2 diabetes. Epigenetic modification, such as DNA methylation, is considered one possible underlying mechanism. The 1998 Quebec ice storm provides a unique opportunity to study an independent prenatal stressor on child outcomes. C-peptide is the best measure of endogenous insulin secretion and is widely used in the clinical management of patients with diabetes. The objectives ...[more]

PMID: 29401509

Similar Datasets

Project description:Introduction: The amygdala is a brain structure involved in emotional regulation. Studies have shown that larger amygdala volumes are associated with behavioral disorders. Prenatal maternal depression is associated with structural changes in the amygdala, which in turn, is predictive of an increase in behavioral problems. Girls may be particularly vulnerable. However, it is not known whether disaster-related prenatal maternal stress (PNMS), or which aspect of the maternal stress experience (i.e., objective hardship, subjective distress, and cognitive appraisal), influences amygdala volumes. Nor is it known whether amygdala volumes mediate the effect of PNMS on behavioral problems in girls and boys. Aims: To assess whether aspects of PNMS are associated with amygdala volume, to determine whether timing of exposure moderates the effect, and to test whether amygdala volume mediates the association between PNMS and internalizing and externalizing problems in 11½ year old children exposed in utero, to varying levels of disaster-related PNMS. Methods: Bilateral amygdala volumes (AGV) and total brain volume (TBV) were acquired using magnetic resonance imaging, from 35 boys and 33 girls whose mothers were pregnant during the January 1998 Quebec Ice Storm. The mothers' disaster-related stress was assessed in June 1998. Child internalizing and externalizing problems were assessed at 11½ years using the Child Behavior Checklist (CBCL). Hierarchical regression analyses and mediation analyses were conducted on boys and girls separately, controlling for perinatal and postnatal factors. Results: In boys, subjective distress was associated with larger right AGV/TBV when mothers where exposed during late pregnancy, which in turn explained higher levels of externalizing behavior. However, when adjusting for postnatal factors, the effect was no longer significant. In girls, later gestational exposure to the ice storm was associated with larger AGV/TBV, but here, higher levels of objective PNMS were associated with more externalizing problems, which was, in part, mediated by larger AGV/TBV. No effects were detected on internalizing behaviors. Conclusion: These results suggest that the effects of PNMS on amygdala development and externalizing symptoms, as assessed in boys and girls in early adolescence, can be influenced by the timing of the stress in pregnancy, and the particular aspect of the mother's stress experience.

Dataset Information

DNA methylation mediates the effect of maternal cognitive appraisal of a disaster in pregnancy on the child's C-peptide secretion in adolescence: Project Ice Storm.

Publications

DNA methylation mediates the effect of maternal cognitive appraisal of a disaster in pregnancy on the child's C-peptide secretion in adolescence: Project Ice Storm.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets