Differentially Methylated Genes in Saliva are linked to Childhood Stress

Abstract

Chronic and severe stress exposure in early childhood is associated with the development of psychiatric disorders. Yet, the molecular mechanisms underlying this relationship remain poorly understood. Here, we profile molecular marks (DNA methylation and gene expression) throughout the human genome to determine the associations between childhood stress exposure and gene regulation. To do so, we collected saliva tissue from prepubertal girls (mean age 10.9 ± 1.26 years) who had experienced different levels of childhood adversity, ranging from mild to severe. We found 122 differentially methylated genes (FDR P-value < 0.05) associated with high childhood stress exposures that affect brain development. Of these differentially methylated genes, 12 also differed in gene expression. To further investigate the potential effects of stress exposure on gene regulation, we examined the DNA sequences flanking all the differentially methylated loci. This analysis revealed enrichment of known binding sites for transcription factors, suggesting that DNA methylation may regulate gene expression by mediating transcription factor binding on these genes. Together, these findings indicate a possible neuromolecular mechanism linking children’s social experiences with risk for anxiety and depressive disorders.

Large epigenome-wide association study of childhood ADHD identifies peripheral DNA methylation associated with disease and polygenic risk burden

“…Epigenetic variation can be influenced by environmental exposures. In fact, many of the environmental risk factors associated with ADHD have been associated with changes in DNA methylation in peripheral tissues [12][13][14][15][16] . Epigenetic changes may also be induced by exposures related to the disease (e.g., medication) or the pathological process itself.…”

How Developmental Neuroscience Can Help Address the Problem of Child Poverty

“…There are consistent relationships between high levels of stress exposure and disruption of the hypothalamic-pituitary-adrenal (HPA) axis (Koss & Gunnar, 2017;Strüber, Strüber, & Roth, 2014), autonomic nervous system (Esposito, Koss, Donzella, & Gunnar, 2016), and immune system functioning (Danese & Lewis, 2017;Danese -cite this issue;Miller & Chen, 2010;Müller et al, 2019), as well as epigenetic changes, especially in the glucocorticoid receptor gene (Papale, Seltzer, Madrid, Pollak, & Alisch, 2018;Romens & Pollak, 2015;Turecki & Meaney, 2016;Tyrka, Price, Marsit, Walters, & Carpenter, 2012). These are systems that have implications for issues of behavioral regulation, academic performance, and health.…”

How Developmental Neuroscience Can Help Address the Problem of Child Poverty

“…There are consistent relationships between high levels of stress exposure and disruption of the hypothalamic-pituitary-adrenal (HPA) axis (Koss & Gunnar, 2017;Strüber, Strüber, & Roth, 2014), autonomic nervous system (Esposito, Koss, Donzella, & Gunnar, 2016), and immune system functioning (Danese & Lewis, 2017;Danese -cite this issue;Miller & Chen, 2010;Müller et al, 2019), as well as epigenetic changes, especially in the glucocorticoid receptor gene (Papale, Seltzer, Madrid, Pollak, & Alisch, 2018;Romens & Pollak, 2015;Turecki & Meaney, 2016;Tyrka, Price, Marsit, Walters, & Carpenter, 2012). These are systems that have implications for issues of behavioral regulation, academic performance, and health.…”