Maternal–infant interaction quality is associated with child NR3C1 CpG site methylation at 7 years of age

Abstract

Objective Infancy is both a critical window for hypothalamic–pituitary–adrenal (HPA) axis development, and a sensitive period for social–emotional influences. We hypothesized that the social–emotional quality of maternal–infant interactions are associated with methylation of HPA‐axis gene NR3C1 later in childhood. Methods Using a subsample of 114 mother‐infant pairs from the Avon Longitudinal Study of Parents and Children (ALSPAC), linear regression models were created to predict variance in methylation of seven selected CpG sites from NR3C1 in whole blood at age 7 years, including the main predictor variable of the first principal component score of observed maternal–infant interaction quality (derived from the Thorpe Interaction Measure at 12 months of age) and covariates of cell‐type proportion, maternal financial difficulties and marital status at 8 months postnatal, child birthweight, and sex. Results CpG site cg27122725 methylation was negatively associated with warmer, more positive maternal interaction with her infant (β = 0.19, p = .02, q = 0.13). In sensitivity analyses, the second highest quartile of maternal behavior (neutral, hesitant behavior) was positively associated with cg12466613 methylation. The other five CpG sites were not significantly associated with maternal–infant interaction quality. Conclusions Narrow individual variation of maternal interaction with her infant is associated with childhood methylation of two CpG sites on NR3C1 that may be particularly sensitive to environmental influences. Infancy may be a sensitive period for even small influences from the social–emotional environment on the epigenetic determinants of HPA‐axis function.

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“…For example, early life stress is associated with epigenetic alterations of the NR3C1 gene encoding the glucocorticoid receptor (GR), with subsequent glucocorticoid resistance and development of depression (Palma-Gudiel et al, 2015). Recently, similar alterations of the gene were also found in infants of cold or hesitant mothers, and persisted until the children were assessed 6 years later (Holdsworth et al, 2023). These results present a possible mechanism explaining previous findings that uncertain childhood environments and adversity can cause sustained dysfunction in CRH-releasing neurons, and increase vulnerability to stressors later in life (Arborelius et al, 1999).…”

Mental health and well-being in children and adolescents

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