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Chronic Stress Leaves Mark on Depression, Bipolar Genes

Chronic release of ordinary stress hormones may leave a long-term mark on the genome and influence the expression of genes responsible for mood and behavior, says a new study led by Johns Hopkins researchers.

These findings could eventually change how scientists and physicians explain and treat depression, bipolar disorder, and other mental illnesses.

Depression, an often debilitating disorder, will affect about 16 percent of the population. Research has shown that the risk of depression is only about 40 percent genetic, a small percentage when compared to other types of mental illnesses, often considered strongly heritable.

Previous research has shown that living a stressful life can increase the risk of depression, but scientists are still unsure of how these life events play into the biology of this disease.

James Potash, M.D.,M.P.H., an associate professor at the Johns Hopkins University School of Medicine, and his team suspected that epigenetic factors might be at work in the development of depression.

Epigenetic (meaning above the genome) factors are aptly named because they influence how genes are expressed without actually changing the genetic sequence. One of the most prevalent epigenetic changes, or marks, are methyl chemical groups that attach onto DNA, often shutting off the gene.

To see if stress could manipulate epigenetic marks on genes involved in depression, Potash and his Johns Hopkins colleagues, including study co-leader Gary Wand, M.D., a professor in the Division of Endocrinology, assistant professor Kellie Tamashiro, Ph.D., and postdoctoral fellow Richard Lee, Ph.D., put corticosterone in the drinking water of some mice for four weeks. Corticosterone is the mouse version of cortisol, a human hormone produced during stressful situations. Other control mice drank plain water.

At the end of four weeks, the mice who drank corticosterone showed anxious characteristics in behavioral tests. The mice were then given gene expression tests which proved a definite increase in protein produced by a gene called Fkbp5. This gene’s human form is linked to mood disorders, including depression and bipolar disease.

When the scientists analyzed the corticosterone rodents’ DNA for epigenetic marks on Fkbp5, they discovered far fewer methyl groups attached to this gene compared with those that drank plain water. These differences in epigenetic marks continued for weeks even after the mice stopped receiving the hormone, suggesting a long-lasting change.

“This gets at the mechanism through which we think epigenetics is important,” says Potash, who directs Johns Hopkins’ Mood Disorders Research Programs.

“If you think of the stress system as preparing you for fight or flight, you might imagine that these epigenetic changes might prepare you to fight harder or flee faster the next time you encounter something stressful.”

However, this preparation for future stress isn’t as beneficial for humans who can’t fight or flee stressors, such as work deadlines, Potash adds. Instead, constant stress might lead to depression or another mood disorder triggered by epigenetic changes.

Eventually, physicians may be able to look for these epigenetic DNA changes in a patient’s blood and predict or confirm psychiatric illnesses, adds Potash. The hope is that researchers will be able to target these epigenetic marks with drugs to treat depression and other diseases.

The study is published in the September issue of Endocrinology.

Johns Hopkins University

Chronic Stress Leaves Mark on Depression, Bipolar Genes

Traci Pedersen

Traci Pedersen is a professional writer with over a decade of experience. Her work consists of writing for both print and online publishers in a variety of genres including science chapter books, college and career articles, and elementary school curriculum.

APA Reference
Pedersen, T. (2018). Chronic Stress Leaves Mark on Depression, Bipolar Genes. Psych Central. Retrieved on September 30, 2020, from
Scientifically Reviewed
Last updated: 8 Aug 2018 (Originally: 17 Sep 2010)
Last reviewed: By a member of our scientific advisory board on 8 Aug 2018
Published on Psych All rights reserved.