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New Findings Cast Doubt on Serotonin Gene-Depression Link
A reexamination of data from studies involving more than 40,000 people has found, contrary to popular thought, no evidence that a particular variant of a serotonin transporter gene increases the risk of depression when a person is exposed to stress.
Researchers published their findings online in Molecular Psychiatry.
“The hypothesis that the S allele of the 5-HTTLPR serotonin transporter promoter region is associated with increased risk of depression, but only in individuals exposed to stressful situations, has generated much interest, research, and controversy since first proposed in 2003,” researchers wrote. “Multiple meta-analyses combining results from heterogeneous analyses have not settled the issue.”
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Led by researchers from the Washington University School of Medicine in St. Louis, Missouri, the new investigation reanalyzed data from multiple studies that followed the influential 2003 paper. Since its publication in Science, the paper has been cited more than 4,000 times by other researchers, and 100 additional published studies have also probed for links among the serotonin gene, stress, and depression. Some found that individuals with the gene variant were more likely to develop depression when exposed to stress, while others found no such likelihood.
The reanalysis looked at information from more than 40,000 people involved in the additional studies.
“Our goal was to get everyone who had gathered data about this relationship to come together and take another look, with each research team using the same tools to analyze data the same way,” said study first author Robert C. Culverhouse, PhD, an assistant professor of medicine and of biostatistics at Washington University. “We all ran exactly the same statistical analyses, and after combining all the results, we found no evidence that this gene alters the impact stress has on depression.”
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“The idea that differences in the serotonin gene could make people more prone to depression when stressed was a very reasonable hypothesis,” said senior investigator Laura Jean Bierut, MD, a psychiatry professor at Washington University. “But when all of the groups came together and looked at the data the same way, we came to a consensus. We still know that stress is related to depression, and we know that genetics is related to depression, but we now know that this particular gene is not.”
—Jolynn Tumolo
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