Epigenetic Vestiges of Early Developmental Adversity: Childhood Stress Exposure and DNA Methylation in Adolescence

University of Wisconsin School of Medicine and Public Health University of British Columbia University of Wisconsin School of Medicine and Public Health University of British Columbia.
Child Development (Impact Factor: 4.92). 09/2011; 84(1). DOI: 10.1111/j.1467-8624.2011.01641.x
Source: PubMed


Fifteen-year-old adolescents (N = 109) in a longitudinal study of child development were recruited to examine differences in DNA methylation in relation to parent reports of adversity during the adolescents' infancy and preschool periods. Microarray technology applied to 28,000 cytosine-guanine dinucleotide sites within DNA derived from buccal epithelial cells showed differential methylation among adolescents whose parents reported high levels of stress during their children's early lives. Maternal stressors in infancy and paternal stressors in the preschool years were most strongly predictive of differential methylation, and the patterning of such epigenetic marks varied by children's gender. To the authors' knowledge, this is the first report of prospective associations between adversities in early childhood and the epigenetic conformation of adolescents' genomic DNA.

Download full-text


Available from: Marilyn J Essex
  • Source
    • "Several EWAS, including those for prenatal exposure to smoking and arsenic [Joubert et al., 2012; Koestler et al., 2013], have quantified DNA methylation in cord blood. This strategy to assess epigenetic perturbation as near as possible to the prenatal period remains a high priority in light of the fetal origins of human disease hypothesis [Barker, 1998; Essex et al., 2013; Armstrong et al., 2014; Babenko et al., 2014]. Whole blood is a desirable matrix to use for EWAS as it is readily available and has been obtained for many human studies with a wide variety of initial aims (including past genome-wide association studies (GWAS)) [Michels et al, 2013; Chadwick et al, 2014; Liang and Cookson, 2014; Lowe and Rakyan, 2014]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Confounding by cellular heterogeneity has become a major concern for epigenome-wide association studies (EWAS) in peripheral blood samples from population and clinical studies. Adjusting for white blood cell percentage estimates produced by the minfi implementation of the Houseman algorithm (minfi) during statistical analysis is now an established method to account for this bias in adults. However, minfi has not been benchmarked against white blood cell counts in children that may differ substantially from the reference dataset used in its estimation. We compared estimates of white blood cell type percentages produced by two methods, minfi and differential cell count (DCC), in a birth cohort at two time points (birth and 12 years of age). We found that both minfi and DCC had similar trends as children aged, and neither count method differed by sex among newborns (P > 0.10). However, minfi estimates did not correlate well with DCC in samples from newborns (ρ = −0.05 for granulocytes; ρ = −0.03 for lymphocytes). In older children, correlation improved substantially (ρ = 0.77 for granulocytes; ρ = 0.75 for lymphocytes), likely due to increasing similarity with minfi's adult reference data as children aged. Our findings suggest that the minfi method may provide suitable estimates of white blood cell composition for samples from adults and older children, but may not currently be appropriate for EWAS involving newborns or young children. Environ. Mol. Mutagen., 2015. © 2015 Wiley Periodicals, Inc.
    Full-text · Article · Aug 2015 · Environmental and Molecular Mutagenesis
  • Source
    • "A number of studies have found differential methylation of several other genes, including those that regulate GR function and other components of the biological response to stress (Lutz & Turecki, 2013), and recent work demonstrates moderating influences of some of these genes on NR3C1 methylation in relation to stress exposure (Klengel et al., 2013; Melas et al., 2013). Recent genome-wide studies of childhood adversity and/or PTSD have identified differentially methylated genes across the genome (Essex et al., 2013; Lutz & Turecki, 2013; Smith et al., 2011). It should be noted, however, that large arrays , which examine hundreds of thousands of genes, may not identify individual genes of interest due to reduced sensitivity or reduced coverage of CpG sites in each gene. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Epigenetic modifications to the genome are a key mechanism involved in the biological encoding of experience. Animal studies and a growing body of literature in humans have shown that early adversity is linked to methylation of the gene for the glucocorticoid receptor (GR), which is a key regulator of the hypothalamic-pituitary-adrenal axis as well as a broad range of physiological systems including metabolic and immune function. One hundred eighty-four families participated, including n = 74 with child welfare documentation of moderate-severe maltreatment in the past 6 months. Children ranged in age from 3 to 5 years, and were racially and ethnically diverse. Structured record review and interviews in the home were used to assess a history of maltreatment, other traumas, and contextual life stressors, and a composite variable assessed the number exposures to these adversities. Methylation of regions 1D, 1F, and 1H of the GR gene was measured via sodium bisulfite pyrosequencing. The composite measure of adversity was positively correlated with methylation at exons 1D and 1F in the promoter of the GR gene. Individual stress measures were significantly associated with a several CpG sites in these regions. GR gene methylation may be a mechanism of the biobehavioral effects of adverse exposures in young children.
    Full-text · Article · May 2015 · Development and Psychopathology
  • Source
    • "A critical issue for the study of the developmental origins of psychopathology is that of how the influences of the early environment are biologically embedded, and thus exert an enduring influence on neural function. Studies over the past decade reveal stable effects of environmental conditions, including parental " signals, " on the epigenome in brain regions associated with affective illness (Champagne, 2012; Essex et al., 2013; Heim & Binder, 2012; Labonte et al., 2012; McGowan et al., 2009; Roth & Sweatt, 2011; Zhang & Meaney, 2010). These epigenetic marks control the structure and function of the genome, and potentially explain variations in genotype–phenotype relations (i.e., identical twins). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Early life environments interact with genotype to determine stable phenotypic outcomes. Here we examined the influence of a variant in the brain-derived neurotropic factor (BDNF) gene (Val66Met), which underlies synaptic plasticity throughout the central nervous system, on the degree to which antenatal maternal anxiety associated with neonatal DNA methylation. We also examined the association between neonatal DNA methylation and brain substructure volume, as a function of BDNF genotype. Infant, but not maternal, BDNF genotype dramatically influences the association of antenatal anxiety on the epigenome at birth as well as that between the epigenome and neonatal brain structure. There was a greater impact of antenatal maternal anxiety on the DNA methylation of infants with the methionine (Met)/Met compared to both Met/valine (Val) and Val/Val genotypes. There were significantly more cytosine-phosphate-guanine sites where methylation levels covaried with right amygdala volume among Met/Met compared with both Met/Val and Val/Val carriers. In contrast, more cytosine-phosphate-guanine sites covaried with left hippocampus volume in Val/Val infants compared with infants of the Met/Val or Met/Met genotype. Thus, antenatal Maternal Anxiety × BDNF Val66Met Polymorphism interactions at the level of the epigenome are reflected differently in the structure of the amygdala and the hippocampus. These findings suggest that BDNF genotype regulates the sensitivity of the methylome to early environment and that differential susceptibility to specific environmental conditions may be both tissue and function specific.
    Full-text · Article · Feb 2015 · Development and Psychopathology
Show more