When the going gets tough, some people barely notice. Others, weighed down by the stress of being fired or losing a loved one, become depressed. Research published today in the journal Science indicates that variation in a single gene more than doubles a person's chances of succumbing to depression in response to life's stresses.

Serotonin has long been linked with depression--many antidepressant medications affect the neurotransmitter's pathway in the brain. In the new work, an international team led by Avshalom Caspi of King's College London investigated the so-called serotonin transporter gene, 5-HTT. This gene codes a protein that recycles the chemical messenger after it has been released by neurons. The researchers studied 847 people born in the early 1970s to determine which variant of 5-HTT they carried, either the long or short form, and an ongoing health study provided details about the number of stressful events they had dealt with over the course of their lives. According to the report, people with two copies of the short variant were two and a half times more likely to become depressed following multiple stressful experiences than subjects who carried two copies of the long variant. In addition, only having the long form appears to confer protection against the condition after surviving traumatic events: subjects with two long alleles had the same rates of depression regardless of how many stressful episodes they had experienced.

"We are not reporting a gene that causes a disease," study co-author Terrie Moffitt of King's College London cautions. "Instead, we believe the gene helps influence whether people are resistant to the negative psychological effects of the unavoidable stresses of life." Although the findings are promising, the authors caution that they cannot yet form the basis for screening for depression. Says Moffitt: "If replication studies confirm that genotypes can predict in advance who is vulnerable to life stresses that bring on depression, this new knowledge could advance efforts to develop a diagnostic test of vulnerability to depression."

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