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Serotonin transporter genotype not linked to depression

Reuters Health • The Doctor's Channel Daily Newscast

NEW YORK (Reuters Health) – The genotype for the serotonin transporter (5-HTTLPR) is not a risk factor for depression, nor does it interact with stressful life events to affect the risk, according to a report in the Journal of the American Medical Association for June 17.

There has been some evidence that 5-HTTLPR polymorphisms work together with stressful life events to affect the risk of depression, but the supporting data is far from conclusive.

To clarify the interaction, if any, Dr. Neil Risch, from the National Institutes of Health, Bethesda, Maryland, and colleagues conducted a meta-analysis of data from 14 studies identified through a search of PubMed, EMBASE, and PsycINFO. Data on 14,250 subjects, including 1769 with depression, were included in the analysis.

Consistent with prior research, the number of stressful life events was identified as a risk factor for depression. Compared with no stressful life events, one, two, and three or more such events increased the odds of major depression by 1.31-, 1.95-, and 3.21-fold, respectively.

Based on the number of short and long alleles, the 5-HTTLPR genotype was classified as SS, SL, or LL. None of these genotypes were significantly linked to depression, nor did they interact with stressful life events to affect the risk.

Further analysis showed that null findings applied to both men and women, the authors note.

“The results of this meta-analysis clearly demonstrate that stressful life events have a potent relationship with the risk of depression, an association that has been one of the most widely studied environmental factors for a range of mental disorders,” Dr. Risch’s team concludes.

“Addition of the serotonin transporter genotype did not improve the prediction of risk of depression beyond that associated with exposure to negative life events,” they add.

JAMA 2009;301:2462-2471.