Stress-Induced DNA Changes May Be Biomarkers of Major Depression in Women

Stress-Induced DNA Changes May Be Biomarkers of Major Depression in Women

Posted: September 15, 2015

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From The Quarterly, Summer 2015

Women with major depression have physical alterations to their DNA that could be caused by stress, new research shows. In a study examining the genomes of more than 11,000 women, scientists have discovered two molecular signatures linked with major depression: a higher than usual amount of mitochondrial DNA (the subset of DNA that is contained in cells’ tiny energy factories) and shorter-than-expected telomeres (protective structures that cap the ends of chromosomes). In experiments with mice, the researchers showed that such changes can result from stress.

The research is notable in part because of the urgency in finding biological markers of depression. The new study was conducted by a large international team led by 2007 NARSAD Distinguished Investigator Jonathan Flint, M.D., of the Wellcome Trust Centre for Human Genetics in the U.K. Among Dr. Flint’s colleagues on the study are two-time (2000, 2010) Distinguished Investigator and Scientific Council member Kenneth Kendler, M.D., of Virginia Commonwealth University; and 2007 Young Investigator grantee Gerome Breen, Ph.D. Their report appeared May 4th in Current Biology.

The study provides clues that could help scientists understand the link between stress and major depression. It also suggests potential tools to help doctors better diagnose and monitor the disease.

As Dr. Flint and his colleagues analyzed the DNA of 5,864 women with recurrent major depression and 5,783 women without depression, they noticed that women with a history of depression had more mitochondrial DNA than the others. The telomere end-caps on their chromosomes were shortest in this group, as well. The DNA of women who had not experienced major depression did not share these features, even if those women had experienced childhood sexual abuse or other stressful life events.

According to the researchers, changes in the amount of mitochondrial DNA likely reflect changes to the function of mitochondria, which might be caused by metabolic changes in response to stress. Telomeres naturally shorten as we age, but some studies have found this process is accelerated in people with high levels of stress or anxiety.

The team designed laboratory experiments to test whether stressful conditions could trigger the kinds of molecular changes they had observed in the DNA of women with depression. Mice that experienced four weeks of stress did indeed develop shortened telomeres and greater amounts of mitochondrial DNA. However, normal telomere length and amounts of mitochondrial DNA amounts were restored after stressful conditions were eliminated.

There’s no evidence that the molecular changes the team has uncovered actually cause depression, the scientists say. But these changes do represent a molecular signature of the illness that could help doctors diagnose the illness and monitor the effectiveness of its treatment.

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