J. Am. Med. Assoc. 301, 2462–2471 (2009)

An analysis of the literature affirms doubts about a much-hailed gene–environment link for depression.

In 2003, researchers found that individuals with specific versions of the serotonin receptor gene 5-HTTLPR are more susceptible to depression when challenged by stressful life events (Science 301, 386–389; 2003). The finding made intuitive sense, and many studies attempted to replicate and build on the results.

Now, Kathleen Ries Merikangas at the National Institute of Mental Health in Bethesda, Maryland, and her colleagues have evaluated the original study together with 13 others that closely replicated its conditions, re-coding data where necessary to match the original. Looking at a total of more than 14,000 study participants, they find no association between 5-HTTLPR type and risk of depression, regardless of life events.