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‘Depression Gene’ Linked to Response to Stress

An analysis of 54 studies suggests that there really is a depression gene that can affect how people respond to stressful life events.

Jan. 4, 2011 -- An analysis of 54 studies suggests that there really is a depression gene that can affect how people respond to stressful life events.

The new study, which appears in the Jan. 3 issue of the Archives of General Psychiatry, should help resolve controversy regarding the role of this gene.

People with a short variation of the serotonin transporter (5-HTTLPR) gene are more likely to become depressed when faced with certain stressful life events than their counterparts who have the longer variation, the new study showed.

What’s more, not all stressful life events are created equally when it comes to depression risk. For example, this gene raises risk of depression in people who have experienced stress related to childhood maltreatment and severe medical illness as opposed to other stressful events.

The “depression gene” was first put on the radar in 2003, and much hope was pinned on this gene. Its discovery was heralded as one of the greatest advances of the year. Things changed dramatically in 2009 after an analysis of 14 studies cast doubt on the gene’s effect on the relationship between stress and depression.

The new analysis included 54 studies published from 2001 and 2010 of more than 41,000 people. The results of the analysis show strong evidence that the short 5-HTTLPR gene does, in fact, affect an individual's ability to develop depression under stress.

“This is the final word,” says Srijan Sen, MD, PhD, an assistant professor in the department of psychiatry in Ann Arbor, Mich.

“A lot of resources and money have gone into looking at this one specific gene and whether it has an association with risk of depression, and now we can move as a field to look more broadly across the human genome to find other genes involved in depression,” he says. “This meta-analysis includes three or four times as many studies, and clearly there is an effect.”

Gene Testing Not Advised

Researchers still don’t know how this gene affects depression risk. “It seems like people who have the short genetic variant are more reactive to positive and negative events,” Sen says. “They react more emotionally in both ways.”

No one should go out and get tested for this gene given the small effect it has on depression risk, he says.

That said, discoveries like this one will help usher in the era of personalized medicine for the treatment of depression.

Depression still has a stigma associated with it, but “the more and more of the biology we figure out, the more we can at combat the stigma associated with depression,” Sen says.

In addition, this line of research can pave the way toward more effective treatments for depression, he says. “Identifying genes can help us identify what is happening in the brain and this will help us develop much better treatments for depression.”

George Tesar, MD, a psychiatrist at the Cleveland Clinic in Ohio, says this genetic variation “is not a cause of depression, but a factor that increases risk of depression in certain individuals.”

It is not a given that if you have this gene, you will develop depression when you experience a stressful situation, he says.

“This article resurrects [the depression gene,] in a fashion, but it never died,” Tesar says. “People still stand by this as a variable.”

When this gene was first discovered in 2003, people in the field wanted it to be the variable to help guide clinical decision making.

It is not the variable, but a variable, Tesar says.

Rudolf Uher, PhD, a clinical lecturer at the Institute of Psychiatry in London, says in a news release that the new study “gives a very clear answer: the 'short' variant of the serotonin transporter does make people more sensitive to the effects of adversity."

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