Abstract
The present study examined the effect of early life stress (ELS) on the glucocorticoid receptor gene (NR3C1) methylation, the associations between NR3C1 methylation and behavior problems, and the effect of the program Parents as Teachers (PAT) on NR3C1 methylation. Participants included 132 children, 72 assigned to the PAT intervention group and 60 to the PAT control group. Children were aged 3 years, and were living in psychosocially at-risk families. We assessed NR3C1 methylation of the NGFI-A binding regions of exon 1F via sodium bisulfite sequencing from saliva DNA. Results indicated that (a) children living in families receiving PAT had decreased methylation at one single cytosine-guanine dinucleotides (CpG) site; (b) current maternal depressive symptoms and parental disagreement were predictive of increased methylation of mean NGFI-A and three single CpG sites; and (c) increased methylation of mean NGFI-A and one single CpG site was significantly associated with increased internalizing and externalizing symptoms. In addition, mean NGFI-A was a mediator of the association between parental disagreement and a child's affective problems. These results suggest that PAT may contribute to preventing NR3C1 methylation in preschool children living in psychosocially at-risk situations, and confirm previous findings on the associations between ELS, NR3C1 methylation, and behavior problems.
Highlights
The early life environment is a major contributor to an individual’s developmental trajectory (Shonkoff et al, 2012)
Increased mean NGFI-A methylation was predicted by higher current maternal depressive symptoms (β = .19, t(106) = 2.02, p = .046) and higher levels of parental disagreement (β = .30, t (103) = 3.37, p < .01), while it was not predicted by socioeconomic status (SES) (β = .03, t(109) = .28, p = .778), and by maternal depressive s1 β p s2 β p s3 β p s4 β p s5 β p
The examination of the individual CpG sites revealed that the intervention group (IG) was associated with significantly lower methylation at CpG 1 compared to the control group (CG) (β = −.26, t(123) = −2.9, p < .01)
Summary
The early life environment is a major contributor to an individual’s developmental trajectory (Shonkoff et al, 2012). Chronic stress exposure in early life, referred to in the literature as early life stress (ELS) or toxic stress, increases the risk of adverse behavioral, physical, and mental outcomes throughout life (Shonkoff et al, 2012). Methylation of the glucocorticoid receptor promoter in children: Links with parents as teachers, early life stress, and behavior problems. Cortisol promotes physiological and behavioral changes as part of the fight-or-flight response, which allows the organism to deal with the stressor (van Bodegom et al, 2017). Chronic stress exposure during development causes the HPA axis to adapt, in order to optimize stress responses to future stressors and promote survival of the individual within its environment (McEwen, 2004)
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