LAUSR

STUDY SYNOPSIS Introduction Summary Individual differences in risk for mental disorders over the lifespan are shaped by forces acting before the individual is born—in utero, but likely even earlier, during the mother’s own childhood. The environmental epigenetics hypothesis proposes that sustained effects of environmental conditions on gene expression are mediated by epigenetic mechanisms. Recent human studies have shown that adversities in the early environment are correlated with DNA methylation in childhood. However, these studies are limited by either (1) candidate-gene approaches, which look only at specific genes and CpG sites, precluding a broader understanding of methylation across the genome, or (2) methylome-wide approaches with small sample sizes, (eg, <200), increasing both type I and type II errors. One recent exception is a methylome-wide analysis in 691 children who were followed longitudinally since birth. In this study, Dunn et al. found that 38 CpG sites were differentially methylated in children at 7 years of age following exposure to adversities. However, clear evidence of childhood adversity induced DNA methylation conserved across decades, into adulthood, and whether it is passed on to offspring, is lacking. In the current study, we will test whether adverse experiences in mothers’ childhoods are correlated with DNA methylation in peripheral blood during pregnancy and in cord blood samples from their newborn infants. We expect to find differentially methylated CpG sites in pregnant women and in their newborn infants associated with mothers’ adverse childhood experiences (ACEs), andwe expect the differentially methylated regions to at least partially overlap between mothers and infants, indicating enduring and transmitted impacts of mothers’ ACEs on DNA methylation. As a secondary analysis, we will test women’s depression and anxiety symptoms during pregnancy as a possible mediator of the association between mothers’ ACE exposure and prenatal/ neonatal DNA methylation, given that (1) ACEs have consistently been shown to be associated with perinatal mood and anxiety disorders, and (2) depression and anxiety have been correlated with DNA methylation in adults, and