In a new analysis, scientists have found evidence of accelerated cellular aging within the hippocampus—a brain region that processes and stores memories—in people with major depression. In past research, brain imaging studies have found that this region of the brain is often smaller in people with recurrent major depression than in those without the disorder.

The new study, reported September 15th in the journal Translational Psychiatry, examined protective end caps on DNA molecules called telomeres. Telomeres in many cell types naturally shorten as we age, but in certain cells, they may shrink more rapidly in times of stress. In their analysis, the scientists found that telomeres in  hippocampus cells were about twice as long in healthy subjects as they were in people who had been diagnosed with major depression.

Firoza Mamdani Ph.D., and Adolfo Sequeira, Ph.D., a 2009 NARSAD Young Investigator at the University of California, Irvine, led the study, working with a team of scientists that included 1997 NARSAD Distinguished Investigator William E. Bunney, Jr., M.D.; 2013 NARSAD Distinguished Investigator Steven G. Potkin, M.D.; 1989 NARSAD Young Investigator Stanley J. Watson, M.D., Ph.D.; and BBRF Scientific Council members Jack D. Barchas, M.D., Alan F. Schatzberg, M.D., and Huda Akil, Ph.D. Drs. Potkin and Bunney are also members of BBRF's Scientific Council.

Dr. Sequeira and his colleagues focused on telomeres because earlier studies had found that in blood cells, the natural degradation of these structures is accelerated in people who experience chronic or early childhood stress. They wondered whether cells in the brain might also be susceptible to excessive telomere shortening, and whether—given the link between psychological stress and mental illness—there might be evidence of that degradation in the brains of people with major depression, bipolar disorder, or schizophrenia.

To find out, they analyzed postmortem brain tissue from 40 individuals—10 who had each disorder, plus 10 normal controls. They measured telomere length in five brain regions. Telomeres in different brain regions varied in length, but in the hippocampus, telomeres were consistently shorter among people with major depression than they were in healthy controls. The hippocampus was the only brain region where the researchers found a significant difference in telomere length between control subjects and subjects with any disorder. This suggests the hippocampus may be particularly susceptible to the effects of stress.

When the researchers followed up on these experiments by analyzing gene activity in the hippocampus, they found that several genes that help cells respond to stress behaved differently in people with major depression than they did in healthy individuals. Taken together, the results suggest that accelerated cellular aging in the hippocampus of people with major depression may be stress-induced.

Read the paper.