May 16, 2011

DNA Link To Depression

In two independent studies scientists have separately identified DNA on chromosome 3 that appears to be related to depression.

Depression has long been suggested in studies to be influenced by genetics, with about 20 percent of the population being majorly affected by it at some point in their lives. The new studies have identified up to 90 genes within the DNA to further suggest that the risk of depression is influenced by genetics.

"What's remarkable is that both groups found exactly the same region in two separate studies," says senior investigator Pamela A. F. Madden, PhD, professor of psychiatry at Washington University.

"We were working independently and not collaborating on any level, but as we looked for ways to replicate our findings, the group in London contacted us to say, "ËœWe have the same linkage peak, and it's significant'."

The new findings will not immediately benefit patients as it takes another 10 to 15 years for any new drugs to be developed, but the discovery is an important step toward understanding what may be happening at the genetic and molecular levels, Madden says.

Scientists at King's College London followed more than 800 families in the United Kingdom who have been affected by recurrent depression; while, separately, the Washington University scientists compiled data from 91 families in Australia and another 25 families in Finland, who were heavy smokers.

"Major depression is more common in smokers, with lifetime reports as high as 60 percent in smokers seeking treatment," says lead author Michele L. Pergadia, PhD, research assistant professor of psychiatry at Washington University.

Pergadia continues, "Smokers with depression tend to experience more nicotine withdrawal and may be more likely to relapse when trying to quit. Previous studies suggest that smoking and depression run together in families. In our study, we detected a region of the genome that travels with depression in families of smokers."

Scientists in England focused their research primarily with recurrent depression, even though some families in the study may have included heavy smokers.

Although the two teams gathered their data for two different purposes and in two different ways, the studies' data resulted in the same discovery of a linkage peak on chromosome 3, which suggests that the depressed siblings in the families of both studies carried many of the same genetic variations in that particular DNA region.

The linkage peak is located on a part of the chromosome known to house the metabotropic glutamate receptor 7 gene (GRM7), which have been found by other scientists to be linked to major depression, a press release states.

"These findings are truly exciting," says Gerome Breen, PhD, lead author of the King's College London study. "For the first time, we have found a genetic region associated with depression, and what makes the findings striking is the similarity of the results between our studies."

Regardless of the new findings, neither team has been able to isolate a gene or genes that may contribute to the risk of depression.

"Our linkage findings highlight a broad area," Pergadia says.

"I think we're just beginning to make our way through the maze of influences on depression. The U.K. samples came from families known to be affected by depression. Our samples came from heavy smokers, so one thing we might do as we move forward is try to better characterize these families, to learn more about their smoking and depression histories, in addition to all of their genetic information in this area."

Both studies are published in the May 16 issue of the American Journal of Psychiatry.

The findings signify an important step to understanding how genes influence depression, but there is still work to be done says Peter McGuffin, MB, PhD, director of the Medical Research Council Social, Genetic and Developmental Psychiatry Center at King's College London.

"The findings are groundbreaking," McGuffin says. "However, they still only account for a small proportion of the genetic risk for depression. More and larger studies will be required to find the other parts of the genome involved."


Pergadia ML, et al. A 3p26-3p25 genetic linkage finding for DSM-IV major depression in heavy smoking families. American Journal of Psychiatry, published online May 16, 2011. ajp.psychiatryonline.org

Breen G, et al. A genome-wide significant linkage for severe depression on chromosome 3: the Depression Network Study. American Journal of Psychiatry, published online May 16, 2011. ajp.psychiatryonline.org


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