Researchers Find No Link Between Defective Gene, Mood Disorder

By Jessica Berman
Washington
17 June 2009

US researchers reviewing more than a dozen studies say a defective gene that has been implicated as a cause of major depression does not appear to elevate a person's risk for the mood disorder. The finding is viewed as a setback for researchers trying to identify a genetic basis for depression.

Major depression and other psychiatric disorders tend to run in families. So, researchers have been looking for the genetic culprits that predispose individuals to the mental disorder.

Discovery of an abnormal gene could lead to diagnostic blood tests to determine who is at risk for depression, and could provide an easier target for drugs used to treat the mood disorder.

The U.S. research team of geneticists, public health officials and epidemiologists, led by Kathleen Merikangas of the federally-funded National Institute of Mental Health, concluded after reviewing 14 studies involving over 14,000 individuals that there's no evidence a defective gene is the sole cause of major depression.

While it's long been established that stressful life events such as loss of a job or divorce can trigger depression, not everyone who experiences a major life change becomes depressed.

So, Merikangas and her colleagues sought to test the finding of a much-hailed 2003 study which concluded that stressful life events were more likely to cause depression in people who also had a defective gene governing the transport of the brain chemical serotonin, a mood-stabilizing neural transmitter.

But Merikangas says subsequent studies that attempted to support the finding have been inconsistent.

"So it wasn't clear whether it was a real finding or whether we needed to learn more about the finding before we started to move in the direction of translating it into public health and prevention," said Merikangas.

While researchers found no direct link between the serotonin transporter gene and depression, they did discover the number of stressful life events increased the risk of depression in some individuals.

Peter Zandi, a researcher at Johns Hopkins University School of Public Health who has been looking for a genetic basis for major depression, calls the study's finding discouraging.

"The best way to confirm these sorts of associations is through replication," Zandi said. "And this particular paper that you cite suggests there isn't replicable evidence of this one particular gene which many in the field had been excited about."

Scientists say it is quite likely the serotonin transporter gene, in combination with other defective genes, contributes to depression.

That's because a class of drugs known as serotonin reuptake inhibitors, which include Prozac, Paxil and Zoloft, that target the abnormal transporter gene, relieve the symptoms of depression in some individuals.

Zandi says the study is not the final word on whether the genetic defect plays a major role in the development of depression.

"It's not conclusive evidence that it's not. But by the same token, there isn't conclusive evidence that it is related to depression," said Zandi. "And after many years of trying to figure out what is going on with the genetic causes of depression, we're not there yet."

The findings of the study on a depression gene appear this week in Journal of the American Medical Association.