This article is more than 5 years old. Information may no longer be current.

Stress genotype 5-HTTLPR may not increase depression risk

Recent findings suggested that the association between the S allele of 5-HTTLPR and increased risk for depression is not broadly generalizable and may only be true in limited circumstances.

“The idea that differences in the serotonin gene could make people more prone to depression when stressed was a very reasonable hypothesis,” study researcher Laura Jean Bierut, MD, of Washington University, St. Louis, said in a press release. “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.”

To assess the association between the S allele of the 5-HTTLPR serotonin transporter promoter region and increased risk for depression, researchers conducted new analyses on 31 data sets that included 38,802 European ancestry subjects genotyped for 5-HTTLPR and evaluated for depression and childhood maltreatment or other stressful life events.

Researchers did not find statistically significant associations between stress and 5-HTTLPR genotype for any subgroups or variable definitions.

Conversely, findings were consistent across samples for the main effects of life stressors as a strong risk factor and 5-HTTLPR genotype as having no impact on risk.

“Experts have been arguing about this for years,” Robert C. Culverhouse, PhD, of Washington University, said in the release. “But ultimately the question has to be not what the experts think but what the evidence tells us. We’re convinced the evidence finally has given us an answer: This serotonin gene does not have a substantial impact on depression, either directly or by modifying the relationship between stress and depression.” – by Amanda Oldt

Disclosure: Culverhouse reports no relevant financial disclosures. Please see the study for a full list of relevant financial disclosures.