A gene long thought to be a risk factor for depression when combined with environmental stress doesn’t appear to be associated with increased depression risk after all. That’s the finding of research published in the Journal of the American Medical Association that analyzes pooled data from 14 different studies. A highly publicized paper published in 2003 showed that individuals with a version of a serotonin-system gene, 5-HTTLPR, who experienced more life stressful life events had greater risk of depression. Since then, many scientists have devoted themselves to studying that gene and to research that examines the interaction between genes and environment on mental illness. One company began offering a test of the gene to measure one’s likelihood of getting depressed and clinicians have wondered if they should test their patients as well. But the finding hadn’t been properly replicated, say the authors of the JAMA study, prompting the team to conduct the meta-analysis. “One of the concerns of the research team that we raise [in the paper] is that this needs to be much more carefully filtered before it’s used for prime time with the public,” study author Kathleen Merikangas , referring to the genetic findings, told the Health Blog. Merikangas is a senior investigator at the National Institute of Mental Health. The researchers took data from 14 previously published studies, recoded and re-analyzed them according to the same criteria

as the 2003 study. The results showed there was no relationship between the gene, stressful events and risk of depression, nor between the gene and depression itself. “We do not see that there is evidence for the interaction between the serotonin transporter gene, stressful life events and depression,” Merikangas told the Health Blog. The focus on this particular gene and environment interaction “is somewhat of an oversimplification of the very complicated pathways that lead to both clinical depression and depression that is a human emotion,” she said. Merikangas said that the research team hopes researchers will “think more carefully” about studying gene and environmental interaction. Avshalom Caspi , a Duke professor and one of the authors of the original 2003 study, told the Health Blog in an email that the new JAMA study ignores scientific evidence that indeed shows that the carriers of the gene are excessively vulnerable to stress and “misrepresents” some other studies. Also, he said that the findings in the meta-analysis vary widely and that the quality of the individual studies varies as well. “What is needed is not less research into gene-environment interaction … but more research of better quality, and a more thorough and thoughtful evaluation of it,” Caspi wrote in his email. DNA image via Wikimedia Commons

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Serotonin Gene’s Link With Depression Not Valid, Says Study