Exposure to maternal mood disorder in utero may program infant neurobehavior via DNA methylation of the glucocorticoid receptor (NR3C1) and 11β-hydroxysteroid dehydrogenase type 2 ( 11β-HSD-2), two placental genes that have been implicated in perturbations of the hypothalamic pituitary adrenocortical (HPA) axis. We tested the relations among prenatal exposure to maternal depression or anxiety, methylation of exon 1F of NR3C1 and 11β-HSD-2, and newborn neurobehavior. Controlling for relevant covariates, infants whose mothers reported depression during pregnancy and showed greater methylation of placental NR3C1 CpG2 had poorer self-regulation, more hypotonia, and more lethargy than infants whose mothers did not report depression. On the other hand, infants whose mothers reported anxiety during pregnancy and showed greater methylation of placental 11β-HSD-2 CpG4 were more hypotonic compared with infants of mothers who did not report anxiety during pregnancy. Our results support the fetal programming hypothesis and suggest that fetal adjustments to cues from the intrauterine environment, in this case an environment that could be characterized by increased exposure to maternal cortisol, may lead to poor neurodevelopmental outcomes.

BackgroundPrenatal socioeconomic adversity as an intrauterine exposure is associated with a range of perinatal outcomes although the explanatory mechanisms are not well understood. The development of the fetus can be shaped by the intrauterine environment through alterations in the function of the placenta. In the placenta, the HSD11B2 gene encodes the 11-beta hydroxysteroid dehydrogenase enzyme, which is responsible for the inactivation of maternal cortisol thereby protecting the developing fetus from this exposure. This gene is regulated by DNA methylation, and this methylation and the expression it controls has been shown to be susceptible to a variety of stressors from the maternal environment. The association of prenatal socioeconomic adversity and placental HSD11B2 methylation has not been examined. Following a developmental origins of disease framework, prenatal socioeconomic adversity may alter fetal response to the postnatal environment through functional epigenetic alterations in the placenta. Therefore, we hypothesized that prenatal socioeconomic adversity would be associated with less HSD11B2 methylation.Methods and FindingsWe examined the association between DNA methylation of the HSD11B2 promoter region in the placenta of 444 healthy term newborn infants and several markers of prenatal socioeconomic adversity: maternal education, poverty, dwelling crowding, tobacco use and cumulative risk. We also examined whether such associations were sex-specific. We found that infants whose mothers experienced the greatest levels of socioeconomic adversity during pregnancy had the lowest extent of placental HSD11B2 methylation, particularly for males. Associations were maintained for maternal education when adjusting for confounders (p<0.05).ConclusionsPatterns of HSD11B2 methylation suggest that environmental cues transmitted from the mother during gestation may program the developing fetus’s response to an adverse postnatal environment, potentially via less exposure to cortisol during development. Less methylation of placental HSD11B2 may therefore be adaptive and promote the effective management of stress associated with social adversity in a postnatal environment.

Background Recent work suggests effective emotion regulation may protect against risk of developing coronary heart disease (CHD), but the mechanisms remain unknown. Strategies for regulating emotions vary in how effectively they mitigate potentially toxic effects of stressful life experiences, and therefore may be differentially associated with CHD risk. In this study we examined emotion regulation strategies of reappraisal and suppression in relation to inflammation, a biological state associated with both stress and CHD. We hypothesized that suppression would be associated with elevated inflammation and reappraisal would be associated with lower inflammation. Methods We studied n=379 adult offspring (mean age=42.2 years) of Collaborative Perinatal Project participants, a national cohort of pregnant women enrolled in 1959–1966. Validated measures of two emotion regulation strategies were examined: reappraisal and suppression. Inflammation was measured as plasma C-reactive protein (CRP) levels. We fit multiple linear regression models predicting CRP while controlling for demographic, socioeconomic and health factors, including depressive symptoms, measured across the life course. Results A one standard deviation increase in reappraisal was associated with significantly lower CRP (b = −0.18, se=0.06, p<0.01) controlling for demographics. This relation was somewhat attenuated in life course models, with adulthood body mass index partially explaining the association. A one standard deviation increase in suppression was associated with significantly higher CRP (b=0.21, se=0.05, p<0.001) and this association was not substantively attenuated with further covariate adjustment. Conclusion Adaptive emotion regulation was associated with lower levels of inflammation and maladaptive emotion regulation was associated with higher levels of inflammation. If these associations are confirmed by prospective and experimental studies, such evidence may provide insight into novel targets for interventions to promote health and reduce cardiovascular risk.