Study identifies DNA changes in major depression, suicide

Autopsies usually point to a cause of death, but now a study of brain tissue collected during these procedures may explain an underlying cause of major depression and suicide, according to University of Western Ontario researcher.

Led by Michael O. Poulter, a professor in the Department of Physiology and Pharmacology in the Schulich School of Medicine & Dentistry and scientist at Robarts Research Institute, the international research group also includes Hymie Anisman of the Neuroscience Research Institute at Carleton University.

This international study is the first to show that proteins that modify DNA directly are more highly expressed in the brains of people who commit suicide. These proteins are involved in chemically modifying DNA in a process called epigenomic regulation. The paper is published in Biological Psychiatry.

The researchers compared the brains of people who committed suicide with those of a control group who died suddenly, from heart attacks and other causes.

They found that the genome in depressed people who had committed suicide was chemically modified by a process that is normally involved in regulating the essential characteristics of all cells in the body.

“We have about 40,000 genes in every cell and the main reason a brain cell is a brain cell is because only a small fraction of the genes are turned on,” says Poulter. “The remaining genes that are not expressed are shut down by an epigenetic process called DNA methylation.”

The rate of methylation in the suicide brains was found to be much greater than that of the control group. Importantly, one of the genes they studied was shown to be heavily chemically modified and its expression was reduced. This particular gene plays a major role in regulating brain activity.

“Interestingly enough, adds Poulter, the nature of this chemical modification is long term and hard to reverse, and this fits with depression.

“The whole idea that the genome is so malleable in the brain is surprising. Finding that epigenetic mechanisms continue to influence gene expression is pretty unusual,” says Poulter. "These observations open an entirely new avenue of research and potential therapeutic interventions."

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