Gene for a Serotonin Receptor and Antidepressant Response

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Gene for a Serotonin Receptor and Antidepressant Response

Prescribing according to the patient’s genome comes a little closer.

Symptomatic response to antidepressant medications varies greatly among patients with depression. For example, in one study, only 47% of patients with major depression achieved complete remission after an adequate trial of an antidepressant. In the present investigation, researchers analyzed the possible relation between common genetic variations and treatment response among 1953 patients with major depression who had received citalopram in the multisite Sequenced Treatment Alternatives for Depression (STAR*D) study (see Journal Watch Psychiatry Apr 5 2006). The researchers narrowed their study to 68 candidate genes and 768 associated single-nucleotide polymorphisms (SNPs).

Treatment response was significantly associated with the A allele of the SNP rs7997012 in HTR2A, the gene encoding the serotonin 2A (5-HT2A) receptor, which is down-regulated by citalopram. Homozygosity for the A allele reduced the odds of nonresponse by 16% to 18%. The A allele was more than six times more common among white than black patients (and treatment in STAR*D had been less effective among black participants).

Comment: These findings make a compelling case for the role of the 5-HT2A receptor in response to depression treatment with this SSRI and might account for some racial differences in medication response. Of note, this study was based on selected candidate genes, not on a complete genome-wide scan, and associations between other polymorphisms and antidepressant response are likely to emerge. Other researchers are expected to report findings from STAR*D on SNPs associated with drug metabolism. In the not-too-distant future, office-based testing for specific polymorphisms that is capable of guiding clinicians’ decisions regarding psychotropic medications will be commonplace. The technology is here, currently being tweaked, and will be disseminated over the next few decades.

— Joel Yager, MD

Published in Journal Watch Psychiatry May 17, 2006

Citation(s):

McMahon FJ et al. Variation in the gene encoding the serotonin 2A receptor is associated with outcome of antidepressant treatment. Am J Hum Genet 2006 May; 78:804-14.

Medline abstract (Free)

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