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

ABSTRACT 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, Jul 30, 2015
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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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    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.
    Development and Psychopathology 02/2015; 27(1):137-50. DOI:10.1017/S0954579414001357 · 4.89 Impact Factor
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    • "Thompson and colleagues also noted that DNA methylation from saliva and whole blood were more similar to each other when compared to lymphoblastoid cell lines, presumably due to the effects of transformation and culture conditions [Thompson et al., 2013]. Despite the interest in peripheral tissues other than blood, few studies have utilized saliva samples for genome-wide DNA methylation surveys [Ghadirivasfi et al., 2011; Essex et al., 2013; Melas et al., 2013; Yang et al., 2013]. Saliva is readily collectable, but the proportion of buccal epithelial cells and leukocytes varies between individuals and results in substantial cellular heterogeneity. "
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    ABSTRACT: DNA methylation has become increasingly recognized in the etiology of psychiatric disorders. Because brain tissue is not accessible in living humans, epigenetic studies are most often conducted in blood. Saliva is often collected for genotyping studies but is rarely used to examine DNA methylation because the proportion of epithelial cells and leukocytes varies extensively between individuals. The goal of this study was to evaluate whether saliva DNA is informative for studies of psychiatric disorders. DNA methylation (HumanMethylation450 BeadChip) was assessed in saliva and blood samples from 64 adult African Americans. Analyses were conducted using linear regression adjusted for appropriate covariates, including estimated cellular proportions. DNA methylation from brain tissues (cerebellum, frontal cortex, entorhinal cortex, and superior temporal gyrus) was obtained from a publically available dataset. Saliva and blood methylation was clearly distinguishable though there was positive correlation overall. There was little correlation in CpG sites within relevant candidate genes. Correlated CpG sites were more likely to occur in areas of low CpG density (i.e., CpG shores and open seas). There was more variability in CpG sites from saliva than blood, which may reflect its heterogeneity. Finally, DNA methylation in saliva appeared more similar to patterns from each of the brain regions examined overall than methylation in blood. Thus, this study provides a framework for using DNA methylation from saliva and suggests that DNA methylation of saliva may offer distinct opportunities for epidemiological and longitudinal studies of psychiatric traits. © 2014 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part B Neuropsychiatric Genetics 01/2015; 168(1). DOI:10.1002/ajmg.b.32278 · 3.27 Impact Factor
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    • "Supporting this possibility, increased methylation of the serotonin transporter 5-HTT gene exacerbates links between maternal deprivation in infancy and behavioral stress reactivity among non-human primates (Kinnally et al., 2010). An additional complexity of the role of epigenetics in these links is emerging evidence that stressors in early childhood including inter-parental violence, parental depression, and socio-economic stress, are predictive of DNA methylation in adolescence (Essex et al., 2011; Radtke et al., 2011). This suggests that not only may epigenetic mechanisms contribute to an infant's relative level of susceptibility to family functioning, but that family functioning may also contribute to the epigenetic mechanisms themselves. "
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    ABSTRACT: We call for a genetically informed approach in the examination of infant social and emotional development in family context. We recommend that scholars conceptualize family functioning as occurring on three unique levels: the parent-child dyad, the inter-parental dyad, and whole family functioning. Although advances in the area of understanding genetic variation in infants as a potential moderator of the influence of parent-child dyadic functioning have been made over the past decade, it is time to widen this inquiry to consider genetic variation in infants as a potential moderator of the influence of inter-parental dyadic and whole family functioning as well. A critical review of the literature also calls for additional examination of genetic variation in infants as a moderator of positive contextual influences, the integration of unique temperament variables with studies of infant genotype, consideration of the role of the gene-environment correlation, and epigenetic effects. Furthermore, we call for the application of genetically-informed research methods to these questions. Expanding knowledge in this area has the potential to refine treatment and prevention efforts aimed at promoting infant social and emotional development.
    Frontiers in Genetics 09/2012; 3:167. DOI:10.3389/fgene.2012.00167
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