Epigenetic Intergenerational Transmission: Mothers’ Adverse Childhood Experiences and DNA Methylation

Abstract

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. 1 Bouvette-Turcot A.-A. Meaney M.J. O’Donnell K.J. In: Noll JG, Shale I, eds. Epigenetics and Early Life Adversity: Current Evidence and Considerations for Epigenetic Studies in the Context of Child Maltreatment. The Biology of Early Life Stress. Springer, New York2018: 89-119 Google Scholar , 2 Bustamante A.C. Aiello A.E. Galea S. et al. Glucocorticoid receptor DNA methylation, childhood maltreatment and major depression. J Affect Disord. 2016; 206: 181-188 Crossref PubMed Scopus (61) Google Scholar , 3 Shields AE, Wise LA, Ruiz-Narvaez EA, et al. Childhood abuse, promoter methylation of leukocyte NR3C1 and the potential modifying effect of emotional support. 2016;8:1507–1517. Google Scholar , 4 Non A.L. Hollister B.M. Humphreys K.L. et al. DNA methylation at stress-related genes is associated with exposure to early life institutionalization. Am J Phys Anthropol. 2016; 161: 84-93 Crossref PubMed Scopus (58) Google Scholar , 5 Esposito E.A. Jones M.J. Doom J.R. MacIsaac J.L. Gunnar M.R. Kobor M.S. Differential DNA methylation in peripheral blood mononuclear cells in adolescents exposed to significant early but not later childhood adversity. Dev Psychopathol. 2016; 28: 1385-1399 Crossref PubMed Scopus (44) Google Scholar 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. 6 Dunn E.C. Soare T.W. Zhu Y. et al. Sensitive periods for the effect of childhood adversity on dna methylation: results from a prospective, longitudinal study. Biol Psychiatry. 2019; 85: 838-849 Abstract Full Text Full Text PDF PubMed Scopus (92) Google Scholar However, clear evidence of childhood adversity−induced DNA methylation conserved across decades, into adulthood, and whether it is passed on to offspring, is lacking. Revision to Stage 1 Registered Report, “Epigenetic Intergenerational Transmission: Mothers’ Adverse Childhood Experiences and DNA Methylation”Journal of the American Academy of Child & Adolescent PsychiatryPreviewWe (P. Scorza, C. S. Duarte, S. Lee, H. Wu, J. E. Posner, A. Baccarelli, C. Monk) have submitted a formal amendment to the methods of our published Stage One Registered Report at the Journal of the American Academy of Child and Adolescent Psychiatry ( https://doi.org/10.1016/j.jaac.2020.03.008 ), "Epigenetic Intergenerational Transmission: Mothers’ Adverse Childhood Experiences and DNA Methylation." Full-Text PDF