Gene Variant Could Predict Chance of Depression

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Whether you roll with life's punches or become depressed in the face of stress may be determined, in part, by your genes, according to new research from the University of Michigan.

The study, published in the Archives of General Psychiatry Monday, examined evidence from 54 studies that identified a particular gene variant, often referred to as the depression gene, as a possible determinant in who will and who will not suffer from clinical depression.

Although the predictive power of the gene variant was recently called into question by a smaller 2009 meta-analysis of 14 studies, researchers argue that the gene, 5-HTTLPR, does, indeed, affect a patient's chances of developing depression.

"That [2009] meta-analysis has been criticized for many reasons, mostly because they only include a few of the studies out there on this gene," says Dr. Srijan Sen, assistant professor of psychiatry at the University of Michigan Medical School and co-author on the study.

"We did a meta-analysis of all 54 studies that exist and, overall, we found that the results support [the existence of the gene] pretty strongly."

Although Sen says the gene has a relatively small impact on chances of developing depression, perhaps accounting for five 7 percent of one's likelihood, he hopes that the meta-analysis will help fuel the discovery of other genetic variants that influence depression.

Other genetic variants influencing depression have been reported, he says, but 5-HTTLPR is the only one "we can confidently say is real."

With a greater understanding of the genes that predict a predisposition toward depression, clinicians could better tailor treatment and provide supportive treatment to those at risk of developing depression, Sen says, an advancement that he believes is perhaps only a decade away.

Predicting Depression Through Genetics

The development of psychological illness often involves a complex interplay between environmental, developmental and genetic factors in a patient. Given the relatively small role specific gene variations may play in the equation, what does a "genetic test for depression" really do for psychiatric treatment?

Being able to identify and test for genetic variants that increase one's likelihood of developing depression could enable more effective, individualized treatments for patients, Sen says.

There is preliminary work on the "depression gene" that finds that those with the variant also respond poorly to a class of depression medication known as SSRIs, he notes, so it is possible that genetic research will one day enable psychiatrists to predict which kinds of treatment, both pharmaceutical and therapy-based, will work best for a particular patient.

Knowing a patient's predispositions also makes preventative psychiatric care possible, says Dr. Ken Robbins, clinical professor of psychiatry at the University of Wisconsin-Madison.

"Over the last ten years, there are more and more people looking at how to promote positive emotions instead of just playing defense against the negative ones," he said. "For those with a genetic predisposition towards depression, it will become very important to learn how to promote positive emotions and resilience in these patients to ward off a possible episode of depression."

Being able to pinpoint the genetic factors inherent in a patient may also provide certain patients peace of mind, says Dr. Harold Koenig, director of the Center for Spirituality, Theology and Health and professor of psychiatry and behavioral sciences at Duke University in Durham, N.C.

"Many people feel guilty about being depressed and blame themselves, not realizing that they may have a genetic predisposition that increases their risk above and beyond that which other people face when they deal with environmental stressors," he says.

Such knowledge may decrease the level of distress over their mental illness.

Psychological Prophecy?

But does knowledge of being at risk increase the likelihood that a patient will succumb to depression; a kind of self-fulfilling psychological prophecy? Probably not, Robbins says.

The gene refers to clinical depression, which is a "very serious depression," he says. "I don't think you can talk yourself into or out of that, though worrying about your susceptibility may affect how you are feeling."

It is important to realize that the genetics of depression are at this point only a small piece of the puzzle of treatment, psychiatrists note.

"Most people with the gene -- even when stressed -- do not develop depression," notes Dr. Gary Kennedy, director of the Division of Geriatric Psychiatry at Montefiore Medical Center in New York City, so "the associated risk is real but very small."

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