Small differences in mom’s behavior may show up in the child’s epigenome

Summary: A mother’s social interaction with her child, especially if her behavior is cold or awkward, is correlated with a small increase in the child’s NR3C1 gene methylation. NR3C1 participates in the regulation the HPA axis which plays a critical role in the stress response and cortisol production.

Source: Washington State University

Adding evidence to the importance of early development, a new study links neutral maternal behavior toward infants to epigenetic change in children related to the stress response.

Epigenetics is a DNA-independent molecular process that influences the behavior of genes. In this study, researchers found that mothers’ neutral or awkward behavior with their babies at 12 months was correlated with an epigenetic change called methylation, or the addition of methane and carbon molecules, to a gene called NR3C1 when children were 7 years old. This gene has been linked to regulating the body’s response to stress.

“There is evidence for a relationship between the quality of mother-child interaction and the methylation of this gene although these are small effects in response to relatively small variation in the interaction,” said Elizabeth Holdsworth, biological anthropologist at Washington State University and lead author of the study published in the American Journal of Human Biology.

Other studies have linked extreme stress early in life, such as neglect and abuse, to more dramatic methylation of this particular gene in adults. However, Holdsworth pointed out that the small difference indicated by this study may be an indication of normal human variation and it is difficult to determine if there are any long-term effects.

For this study, Holdsworth and her co-authors analyzed a subsample of 114 mother-child pairs from the Avon Longitudinal Parent-Child Study, a project that follows a cohort of children born in 1991 and 1992 in Avon, UK.

The researchers first analyzed data from an observational study of 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 the primary caregivers of infants. The vast majority of women in this sample were white, college educated, and from middle-income households.

The range of warmth they displayed varied only slightly with the “coldest” behavior classified as bothersome or neutral, but that’s exactly what the researchers hoped to test: that even small differences in social interaction could be related to epigenetic change.

It shows a mother and her son
Other studies have linked extreme stress early in life, such as neglect and abuse, to more dramatic methylation of this particular gene in adults. Image is in public domain

The observed behavior was then compared to data from an epigenetic analysis of children’s blood samples taken at the age of seven. The researchers found that mothers showing awkward or neutral behavior towards their child correlated with a small increase in methylation on the NR3C1 gene.

This gene codes for a receptor involved in regulating the HPA axis, the interaction between the hypothalamus, pituitary and adrenal glands. This axis plays a role in the stress response, including the production of the body’s main “stress” hormone, cortisol.

The HPA axis can be activated by almost anything that requires a rapid release of energy, whether it’s reacting to a real threat, watching a horror movie, or simply exercising.

The NR3C1 gene is known to be involved in activating this axis, but more research is needed to understand how methylation of this gene is associated with the stress response, Holdsworth said, as some studies have shown an increase in methylation linked to hypo-responsiveness or blunted response. while others showed hyper-responsiveness.

Researchers are working to find out how these changes happen, especially during infancy when the body is growing rapidly, and what they might mean.

β€œIn developmental biology, we know that humans grow to adapt to the environment they find themselves in, which contributes to normal human biological variation. It’s not necessarily good or bad,” she said.

About this epigenetics research news

Author: Sara Zaske
Source: Washington State University
Contact: Sara Zaske – Washington State University
Picture: Image is in public domain

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This shows a woman's ear

Original research: Access closed.
“Quality of mother-child interaction is associated with methylation of the child’s NR3C1 CpG site at age 7” by Elizabeth A. Holdsworth et al. American Journal of Human Biology


The quality of mother-child interaction is associated with the methylation of the child’s NR3C1 CpG site at the age of 7 years


Early childhood is both a critical window for the development of the hypothalamic-pituitary-adrenal (HPA) axis and a sensitive period for socio-emotional influences. We hypothesized that the socio-emotional quality of mother-child interactions is associated with HPA axis gene methylation NR3C1 later in childhood.


Using a subsample of 114 mother-child pairs from the Avon Longitudinal Study of Parents and Children (ALSPAC), linear regression models were created to predict variance in methylation of seven sites CpGs selected from NR3C1 in whole blood at 7 years of age, including the primary predictor of the first principal component score of observed quality of mother-infant interaction (derived from Thorpe’s interaction measure at the age of 12 months) and covariates of cell type proportion, mother’s financial difficulties and marital status at 8 months after birth, child birth weight and gender.


Methylation of the CpG site cg27122725 was negatively associated with warmer and more positive maternal interaction with her infant (b = 0.19, p = 0.02, 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 the quality of mother-infant interaction.


Close individual variation in maternal interaction with her child is associated with infantile methylation of two CpG sites on NR3C1 which may be particularly susceptible to environmental influences. Early childhood can be a sensitive time for even small influences of the socio-emotional environment on the epigenetic determinants of HPA axis function.

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