Gene Identified To More Than Doubles Risk Of Depression

The Impact of a Single Gene

Among people who suffered multiple stressful life events over 5 years, 43 percent with one version of a gene developed depression, compared to only 17 percent with another version of the gene, say researchers funded, in part, by the National Institute of Mental Health (NIMH). Those with the "short," or stress-sensitive version of the serotonin transporter gene were also at higher risk for depression if they had been abused as children. Yet no matter how many stressful life events they endured, people with the "long" or protective version experienced no more depression than people who were totally spared from stressful life events. The short variant appears to confer vulnerability to stresses, such as loss of a job, breaking up with a partner, death of a loved one, or a prolonged illness, report Drs. Avshalom Caspi and Terrie Moffitt, University of Wisconsin and King's College London, and colleagues, in the July 18, 2003, Science.

The serotonin transporter gene codes for the protein in neurons, brain cells, that recycles the chemical messenger after it's been secreted into the synapse, the gulf between cells. Since the most widely prescribed class of antidepressants act by blocking this transporter protein, the gene has been a prime suspect in mood and anxiety disorders. Yet, its link to depression eluded detection in eight previous studies.

"We found the connection only because we looked at the study members' stress history," noted Moffitt. She suggested that measuring such pivotal environmental events�which can include infections and toxins as well as psychosocial traumas�might be the key to unlocking the secrets of psychiatric genetics.

Although the short gene variant appears to predict who will become depressed following life stress about as well as a test for bone mineral density predicts who will get a fractured hip after a fall, it's not yet ready for use as a diagnostic test, Moffitt cautioned. If confirmed, it may eventually be used in conjunction with other, yet-to-be-discovered genes that predispose for depression in a "gene array" test that could help to identify candidates for preventive interventions. Discovering how the "long" variant exerts its apparent protective effect may also lead to new treatments, added Moffitt.

Next: How the Gene was Found

Adapted from: Gene More Than Doubles Risk Of Depression Following Life Stresses
(http://www.nimh.nih.gov/press/prgenestress.cfm)

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