Summary: A mother’s social interaction with her child, especially if her behavior is cold or awkward, is correlated with a small increase in methylation of the child’s NR3C1 gene. The NR3C1 is involved in regulating the HPA-axis which plays a critical role in stress response and the production of cortisol.
Source: Washington State University
Adding evidence to the importance of early development, a new study links neutral maternal behavior toward infants with an epigenetic change in children related to stress response.
Epigenetics are molecular processes independent of DNA that influence gene behavior. In this study, researchers found that neutral or awkward behavior of mothers with their babies at 12 months correlated with an epigenetic change called methylation, or the addition of methane and carbon molecules, on a gene called NR3C1 when the children were 7 years old. This gene has been associated with regulating the body’s response to stress.
“There is evidence of a relationship between the quality of maternal-infant interaction and methylation of this gene though these are small effects in response to a relatively small variation in interaction,” said Elizabeth Holdsworth, a Washington State University biological anthropologist and lead author of the study published in the American Journal of Human Biology.
Other studies have connected extreme stress in early life, like neglect and abuse, to more dramatic methylation on this particular gene in adults. However, Holdsworth emphasized that the small difference indicated by this study may be an indication of normal human variation and it’s hard to determine if there are any long-term effects.
For this study, Holdsworth and her co-authors analyzed a subsample of 114 mother-infant pairs from the Avon Longitudinal Study of Parents and Children, a project that tracks a cohort of children born in 1991 and 1992 in Avon, UK.
The researchers first analyzed data from an observational study of the mothers sharing a picture book with their children at 12 months, in which their interactions were coded on warmth. The study focused on mothers because they are often infants’ primary caregivers. The vast majority of the women in this sample were white, college-educated and from middle-income households.
The range of warmth they displayed only varied slightly with the “coldest” behavior classified as awkward or neutral, but this is exactly what the researchers hoped to test: that if even small differences in social interaction could be linked to an epigenetic change.
Other studies have connected extreme stress in early life, like neglect and abuse, to more dramatic methylation on this particular gene in adults. Image is in the public domain
The observed behavior was then compared against data from an epigenetic analysis of the children’s blood samples taken at age seven. The researchers found that the mothers showing awkward or neutral behavior toward their infant correlated with a small increase of methylation on the NR3C1 gene.
This gene encodes a receptor involved in the regulation of the HPA axis—the interaction between the body’s hypothalamus, pituitary and adrenal glands. This axis plays a role in stress response, including production of the body’s primary “stress” hormone, cortisol.
The HPA axis can be activated by almost anything that requires a quick release of energy from reacting to a real threat to watching a scary movie to simply exercising.
The NR3C1 gene is known to be involved in activating this axis, but more research is needed to understand how methylation of that gene is associated with stress response, Holdsworth said, as some studies have shown increased methylation linked to hypo-reactivity, or blunted response while others have shown hyper-reactivity.
Researchers are working to uncover how these changes happen, particularly during infancy when the body is developing rapidly—as well as what they might mean.
“Within developmental biology, we know humans grow to fit the environment that they’re in, which contributes to normal human biological variation. It’s not necessarily good or bad,” she said.
Maternal–infant interaction quality is associated with child NR3C1 CpG site methylation at 7 years of age
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.
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.
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.
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.