There is a growing body of evidence indicating that difficulties, experienced early in life or in the present, can predispose a woman to perinatal depression—depression that develops during pregnancy or in the months after childbirth.  While this theory has plausibility based on studies of depressed mothers, the biological mechanisms through which early-life experiences  might affect the brain and, in turn, the behavior and mood of depressed moms, are not known.

The late Bruce McEwen, Ph.D., of Rockefeller University, a BBRF Scientific Council member, 2005 BBRF Goldman-Rakic Prize winner and 1998 Distinguished Investigator, performed pioneering research showing that chronic stress from early-life adversity could cause behavioral and psychological difficulties by increasing what he called the “allostatic load” in affected individuals. By this he meant wear and tear on bodily systems, including the brain, caused by high levels of stress, and mediated by the release of high levels of stress hormones, among other factors.

Thalia Robakis, M.D., Ph.D., of Stanford University, was awarded a BBRF Young Investigator grant in 2014 to study whether biological evidence of early-life stress as well as other potentially predisposing factors for perinatal depression can be identified and reliably measured. Her project was a basis for a study just published in Translational Psychiatry. In the study, Dr. Robakis and her colleagues report on their efforts to find such biological evidence in modifications of DNA.

The DNA modifications the team studied are called DNA methylation marks, which can be thought of as molecular tags attached to DNA, the genetic material.  DNA methylation marks are part what researchers call the epigenetic apparatus inside each cell. This apparatus regulates gene activity and imparts the cell’s identity (for instance, whether a cell is to be a nerve cell or a liver cell), and it is of particular interest when studying interactions between the genome and the environment.

Dr. Robakis and team members who included 2012 BBRF Young Investigator Alexander Urban, Ph.D., 2003 Distinguished Investigator Ian Gotlib, Ph.D., and 2015 Young Investigator Kathryn Humphreys, Ph.D., studied data from 54 women who were taking part in a multiyear study of perinatal depression. They intentionally oversampled women with histories of mood disorders; all were 18 or older and had uncomplicated pregnancies.

Among their central objectives was to search for links between DNA methylation patterns in samples taken from these women and early-life adversity and “attachment insecurity.” The latter refers to difficulties forming emotional bonds.

The evidence suggested to the team that a new mother’s depression around the time of childbirth may be the result of changes in gene expression caused by changes to the DNA methylation tags on her genome. It is not easily possible to determine when such changes may have occurred. One possibility discussed by the researchers is that DNA methylation tags may be altered early in life, in response to a variety of environmental factors such as stress, adversity, or weak bonding with one’s own parents.

There was evidence that DNA methylation affecting the gene that produces the receptor for oxytocin may be central in this mechanism. Oxytocin is a hormone that is expressed at high levels during social bonding, including after childbirth.

The team’s evidence also suggested that attachment insecurity, or difficulty forming emotional bonds, was more relevant than allostatic load, or wear and tear caused by childhood trauma, in biological pathways connected with perinatal depression.

“Based on this research, we propose that assessments of both childhood adversity and insecure attachment style should be included in evaluation and treatment planning for perinatal psychiatric patients,” the team concluded.