How the stressed become depressed

Some individuals persevere in hardship; others crumple like paper dolls. Mental fortitude in the face of stress has been linked to variations in a gene that regulates the neurotransmitter serotonin: individuals with a short version of the gene have a greater propensity to fall into depression under stress, while those with the longer version are more resilient.

To gain a glimpse of how these genetic differences might interact with stress to produce depression, R. Todd Constable, Ph.D., professor of diagnostic radiology and biomedical engineering, and colleagues in New York and Germany used brain imaging while individuals carrying short or long forms of the gene looked at images of faces.

Other work had suggested that short-gene carriers who had experienced life stress would show an elevated response to sad or fearful faces in brain areas involved in depression and coping.

But in the October 24 issue of Proceedings of the National Academy of Sciences, Constable and colleagues reported less activation in short-gene carriers under these conditions and greater activation at rest. This pattern may reflect “a chronic state of vigilance, threat, or rumination” in short-gene carriers that makes them more vulnerable to depression under stress.