DNA methylation at stress‐related genes is associated with exposure to early life institutionalization

Abstract

Objectives Differences in DNA methylation have been associated with early life adversity, suggesting that alterations in methylation function as one pathway through which adverse early environments are biologically embedded. This study examined associations between exposure to institutional care, quantified as the percent time in institutional care at specified follow-up assessment ages, and DNA methylation status in two stress-related genes: FKBP5 and SLC6A4. Materials and Methods We analyzed data from the Bucharest Early Intervention Project, which is a prospective study in which children reared in institutional settings were randomly assigned (mean age 22 months) to either newly created foster care or care as usual (to remain in their current placement) and prospectively followed. A group of children from the same geographic area, with no history of institutionalized caregiving, were also recruited. DNA methylation status was determined in DNA extracted from buccal epithelial cells of children at age 12. Results An inverse association was identified such that more time spent in institutional care was associated with lower DNA methylation at specific CpG sites within both genes. Discussion These results suggest a lasting impact of early severe social deprivation on methylation patterns in these genes, and contribute to a growing literature linking early adversity and epigenetic variation in children.

Annual Research Review: Early adversity, the hypothalamic–pituitary–adrenocortical axis, and child psychopathology

“…Individuals with exposure to early physical maltreatment demonstrate greater methylation of the NR3C1 gene measured during adolescence (Romens, McDonald, Svaren, & Pollak, ) and adulthood (Bustamante et al., ; however see Tyrka et al., ). Longer time in orphanage care was associated with lower methylation of the FKBP5 gene during adolescence (Non et al., ), something that might put youth at risk for PTSD. Finally, increased NR3C1 methylation mediated between maltreatment during the past 6 months and concurrent internalizing behaviors in preschoolers (Parade et al., ).…”

Towards a Heuristic Research Model Linking Early Socioeconomic Adversity and Youth Cumulative Disease Risk: An Integrative Review

“…In this review, genetic vulnerability is conceptualized as a part of early vulnerability or biological imbedding (Hertzman and Boyce 2010) because genetic disposition can be turned off or on depending on early life experiences (Non et al 2016;Meaney 2010) (path 1a). That is, epigenetic research has shown that experiences, such as adversity, are related to how genes are "expressed" (i.e., phenotypes), and this genetic expression is a determining factor of emotional and behavioral problems (path 1b), psychosocial resources (path 1c), and disease risk (path 1d).…”

When mothering goes awry: Challenges and opportunities for utilizing evidence across rodent, nonhuman primate and human studies to better define the biological consequences of negative early caregiving

“…Similar cross-species support has been reported for the serotonin transporter. Within the Bucharest Early Intervention Project, a randomized trial of institutional care compared to foster care, methylation in the 5HTTLPR in buccal epithelial cells at age 12 was significantly correlated with the amount of time a child spent in institutional care across the life course (Non et al, under review). In humans and NHP models this relationship, as well as the impact on down-stream gene expression appears to be further influenced by the 5HTTLPR genotype, a polymorphic variant not found in rodent species (Kinnally et al, 2010).…”