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.

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Available from: Marilyn J Essex,
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    • "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]. "
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    • "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. "
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    • "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). "
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