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Maternal-infant interaction quality is associated with child NR3C1 CpG site methylation at 7 years of age
Elizabeth A Holdsworth1,2, Lawrence M Schell2,3, Allison A Appleton3
1Department of Anthropology, Washington State University, Pullman, Washington, USA.
Insights
Maternal interaction quality in infancy impacts childhood DNA methylation of the NR3C1 gene, which is crucial for hypothalamic-pituitary-adrenal (HPA) axis development. Early social-emotional experiences can shape epigenetic programming.
Area of Science:
- Developmental Psychology
- Epigenetics
- Neuroendocrinology
Background:
- Infancy is a critical period for hypothalamic-pituitary-adrenal (HPA) axis development.
- Social-emotional influences during infancy can impact long-term HPA axis function.
- The NR3C1 gene plays a key role in regulating the HPA axis.
Purpose of the Study:
- To investigate the association between the quality of maternal-infant interactions during infancy and NR3C1 gene methylation in childhood.
- To identify specific CpG sites within NR3C1 that are sensitive to early social-emotional environments.
Main Methods:
- Utilized data from 114 mother-infant pairs in the Avon Longitudinal Study of Parents and Children (ALSPAC).
- Assessed maternal-infant interaction quality using the Thorpe Interaction Measure at 12 months.
- Employed linear regression models to predict NR3C1 methylation at age 7 years, controlling for covariates.
Main Results:
- CpG site cg27122725 methylation showed a negative association with warmer, positive maternal interactions (p=0.02).
- Sensitivity analyses indicated a positive association between neutral/hesitant maternal behavior and cg12466613 methylation.
- Five other CpG sites within NR3C1 were not significantly associated with interaction quality.
Conclusions:
- Variations in maternal interaction quality during infancy are linked to childhood methylation patterns of specific NR3C1 CpG sites.
- These findings suggest infancy is a sensitive period for social-emotional environmental influences on HPA-axis epigenetic regulation.
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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