Different environmental factors experienced by a child can undoubtedly impact their life in the long run. Whether they were born into poverty, lack access to education, or are surrounded by violence, these experiences have the ability to dramatically disrupt their lives if they’re without the right support system. But, could a mother’s exposure to stress impact her child even before he or she is born? And could the way a mother treats her child buffer any adverse impact? Research on depressed mothers has recently shown that their response to stress can be transferred through the placenta and negatively impact their baby developing in the womb, affecting birth weight, susceptibility to disease, and brain development. Now, researchers are expanding on this evidence and have uncovered an epigenetic connection between maternal depression, sensitivity, and the programming of a child’s stress response system.
In a study conducted at the University of Utah, led by Elisabeth Conradt, scientists looked at how a mother’s hormonal response to stress, exhibited by her neuroendocrine system, epigenetically affected her infant’s hormone release response to stress. This stress reaction in the child is guided by the hypothalamic-pituitary-adrenal (HPA) axis, which describes connections between the hypothalamus, the pituitary gland, and the adrenal glands. The well-known HPA axis creates a hormone known as cortisol, which is produced in reaction to stressful events.
In the paper, titled “The contributions of maternal sensitivity and maternal depressive symptoms to epigenetic processes and neuroendocrine functioning,” the group of scientists relied on a technique used to analyze gene-specific DNA methylation at base-resolution, known as bisulfite conversion, in order to reveal clues about how exposure to a depressed mother’s response to stress can epigenetically affect her infant’s HPA axis. They sought to determine if particular parenting strategies could combat the detrimental impact that maternal depression may have on an infant and whether this buffering is reflected in the child’s epigenome.
Utilizing animal models, previous studies have highlighted epigenetic programming that occurs after birth as a result of the quality of the mother’s care and affection. In this study, the team of researchers wanted to apply what has been learned in animal studies to humans.
“We were curious about whether maternal behavior could “buffer” the child against the effects of maternal depression, and if this buffering could be observed at the level of the infant’s epigenome,” Conradt explained.
Using bisulfite conversion to assess methylation
The team investigated whether the quality of the postnatal environment, for example, maternal sensitivity, is linked to the level of methylation of genes related to the HPA axis and the child’s neuroendocrine functioning. DNA methylation is the addition of a methyl group to DNA via DNA methyltransferases (DNMT), which influences gene expression. In order to assess DNA methylation levels, the researchers employed a common technique used to study DNA methylation on a gene-specific level known as bisulfite conversion. This process converts uracil to thymine while leaving methylated cytosines, known as 5-methylcytosine (5-mC), intact. This allows the distinction to be made between which bases are methylated and which aren’t. Popular downstream applications following the bisulfite conversion of DNA include next-generation sequencing and PCR.
Previous research has demonstrated that there’s often an increase in DNA methylation and a decrease in the activity of genes related to stress when mothers are depressed while pregnant. Therefore, the two key stress-associated genes that the researchers focused on were the glucocorticoid receptor gene (NR3C1) and the 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) gene.
When methylation of 11β-HSD2 is increased, the fetus is exposed to a greater amount of maternal cortisol. When methylation of NR3C1 is increased, this reduces the number of glucocorticoid receptors to which cortisol can bind, thereby leading to an abundance of cortisol in the blood.
Play time and cortisol levels
The researchers assessed 128 infants and mothers who self-reported depressive symptoms. Conradt and her research group aimed to determine whether the methylation of 11β-HSD2 and NR3C1 genes was linked to maternal depression and/or maternal sensitivity. The DNA was obtained from buccal (cheek) samples from the infants in order to apply bisulfite conversion techniques and assess DNA methylation.
For the study’s procedure, the children played with their mothers face-to-face three times. The first time called for normal play between both. However, the second play session required the mothers not to respond to their infants. Finally, the third session acted as a reunion opportunity during which the mothers could interact with their child again. A cortisol sample was collected from each infant before they entered the lab and two samples were collected following the play session in which the mother did not respond to her infant and the reunion play session. After the second play time, the DNA was collected with a simple, unobtrusive cheek swab.
Maternal sensitivity was measured using four scales and recorded every 30 minutes as the mother interacted with the child. The four scales included maternal acceptance, demandingness, responsiveness, and appropriate touch. These aspects were combined to make up the mother’s “maternal sensitivity.”
Sensitivity epigenetically outweighs the impact of stress
Ultimately, the researchers discovered that the more maternal sensitivity the mothers displayed, the lower the baby’s levels of cortisol. Although the infants whose mothers had high maternal sensitivity did not have any differences in DNA methylation levels, those whose mothers had low maternal sensitivity and high depressive symptoms actually had significantly increased methylation and higher levels of cortisol.
Taking their research even further, they found that mothers with depressive symptoms who scored high on maternal sensitivity, specifically those who engaged more in appropriate touching and responded more to their baby, had infants with lower levels of DNA methylation compared to mothers with depressive symptoms who scored low on maternal sensitivity and were considered insensitive.
The results suggest that the infants’ exposure to their mother’s depressive symptoms can be buffered by how sensitive she is towards him or her. Regardless of the mother’s depression, if she is sensitive towards her child, then his or her exposure to mom’s depressive symptoms doesn’t appear to have an impact. This research study is the first of its kind, showing that various types of maternal caregiving might be able to epigenetically impact the child to better cope with stress.
Conradt concluded, “Many mothers struggle with depression but interact quite sensitively with their infants. In these instances, the mother may be “turning on” certain genes that we think allow infants to manage stress in adaptive ways.”
They are now replicating and expanding on this research by using first-time pregnant women in Utah in order to gain a better understanding of whether parenting can buffer or alleviate the impact of prenatal exposure to stress and depression.
Conradt is hopeful for the future: “We are excited about the possibility that this research may lead to specific ways one can effectively intervene with pregnant women at risk for postpartum depression.”
Source: Conradt, E., Hawes, K., Guerin, D., Armstrong, D.A., Marsit, C.J., Tronick, E., Lester, B.M. (2016). The Contributions of Maternal Sensitivity and Maternal Depressive Symptoms to Epigenetic Processes and Neuroendocrine Functioning. Child Development, 87 (1): 73.
Reference: The University of Utah. Mommy and Me. UNews. 11 Feb 2016. Web.
