Maternal Depression Linked to DNA Methylation Changes in Offspring

April 27, 2015

By Will Boggs MD

Maternal depression is associated with widespread changes in DNA methylation in their offspring that may persist into adulthood, researchers from Canada report.

"These data further demonstrate the potential long-term consequences of maternal depression for the health of future generations and the importance of mental health and social support of mothers and would be mothers for the physical health of newborn and children," Dr. Moshe Szyf from McGill University in Montreal, Quebec, told Reuters Health by email. "What is remarkable is that the mental state of a mother causes changes in DNA methylation in the newborns in the immune system, not just the brain."

Maternal mood disorders and stress during pregnancy can result in attention learning deficits during childhood and mood disorders during adulthood for their offspring. Evidence suggests these consequences may be mediated by modifications of DNA methylation levels.

Dr. Szyf's team investigated possible associations between maternal depression and DNA methylation changes in T lymphocytes from neonatal cord blood and in hippocampal brain tissues from adults with or without histories of maternal depression.

In the mothers' own T lymphocytes, there was no association between depressive symptom severity scores (or even depression itself) and the T lymphocyte DNA methylation level.

Offspring of depressed mothers, however, showed significant differences in DNA methylation from those of nondepressed mothers in 145 T lymphocyte CG sites. Most (75.5%) were hypomethylated in the maternal depression group compared with the control group.

Genes associated with the relatively "under-methylated" sites were enriched in biological functions related to immune function, the researchers report in Translational Psychiatry, online April 7.

In the hippocampus of deceased adults whose mothers had been depressed during pregnancy, 234 genes showed differential DNA methylation (compared with adults whose mothers had not been depressed during pregnancy). These differences, too, showed enrichments in immunological-related functions.

Ten of the differentially methylated CG sites in T lymphocytes from neonatal cord blood were within 500 bases of differentially methylated probes in the adult hippocampus.

"One of the main surprises was that we found a larger effect of maternal depression on the babies' DNA methylation than the maternal DNA methylation," Dr. Szyf said. "The second surprise was that it seems that the effect is a consequence of lifelong depression rather than depression only around the pregnancy period."

"For healthy babies to develop into healthy adults it is important to have healthy mothers," Dr. Szyf said. "And this involves not only physical and metabolic health but also mental and social wellbeing. This hopefully will be an important pillar in prenatal care as well as public policy relating to preconception health."

"The epigenetic consequences of maternal depression might suggest using epigenetic interventions for prevention and reversal of the impacts of maternal depression on the offspring," Dr. Szyf added. "One clinical potential of the data is the possibility of developing biomarkers of maternal depression that might serve as predictors of lifelong health risks and guide early interventions."

Dr. Joanne Ryan from University of Melbourne's Murdoch Childrens Research Institute, Australia, who recently reviewed epigenetics and depressive disorders, told Reuters Health by email, "An important next step in this research is to determine whether these methylation differences and associated with health outcomes in the infants/children. Maternal depression during pregnancy has been associated with long-term negative outcomes in the child -- the data from this study should be used to determine whether such effects can be mediated by differential DNA methylation."

"There are no direct clinical implications from this research, although it adds weight to a growing field of studies suggesting the possibility of peripheral biomarkers which would be indicative of perinatal exposure, and used to predict future risk for health outcomes," Dr. Ryan concluded.


Transl Psychiatry 2015.

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