Genetic Variation May Influence Response to Depression Treatment

Variations in a gene known as TREK1 may explain some forms of treatment-resistant major depression, according to a new study analyzing genetic data from the NIMH-funded Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. The study was published online February 20, 2008, in Neuropsychopharmacology.

Scientists have limited knowledge of how certain genes affect individual response to antidepressant treatment. But studies in mice have identified variations of four genes that may be involved. Roy Perlis, M.D., of Massachusetts General Hospital, and colleagues examined these four genes in DNA samples provided by 1,554 STAR*D participants. They found no associations among the four genes and the participants who either responded or did not respond to the trial's first level of treatment. However, the researchers found that in the 751 participants who did not respond to Level 1 and continued with the next level of treatment, those having certain variations in the TREK1 gene were more likely to show treatment resistance. The same association held true among participants who did not respond to Level 2 and continued for a third level of treatment.

SSRIs are known to inhibit TREK1. Mice without the gene are resistant to developing depression-like behaviors, and exhibit behaviors similar to mice treated with antidepressants, indicating that TREK1 could be involved in regulating response to antidepressants.

The researchers note that further study is needed to confirm their findings and determine how these variations interfere with treatment. However, the study adds to the body of research examining the genetic factors that underlie response to depression treatment, ultimately leading to better ways of recognizing and treating patients who may not respond to conventional treatment regimens.

Reference

Perlis RH, Moorjani P, Fagerness J, Purcell S, Trivedi H, Fava M, Rush AJ, Smoller JW. Pharmacogenetic analysis of genes implicated in rodent models of antidepressant response: association of TREK1 and treatment resistance in the STAR*D study. Neuropsychopharmacology. advance online publication February 20, 2008.