Variation in the gene encoding the serotonin 2A receptor is associated with outcome of antidepressant treatment.

Journal Article (Journal Article)

Depressive disorders account for a large and increasing global burden of disease. Although the condition of many patients improves with medication, only a minority experience full remission, and patients whose condition responds to one medication may not have a response to others. Individual variation in antidepressant treatment outcome is, at present, unpredictable but may have a partial genetic basis. We searched for genetic predictors of treatment outcome in 1,953 patients with major depressive disorder who were treated with the antidepressant citalopram in the Sequenced Treatment Alternatives for Depression (STAR*D) study and were prospectively assessed. In a split-sample design, a selection of 68 candidate genes was genotyped, with 768 single-nucleotide-polymorphism markers chosen to detect common genetic variation. We detected significant and reproducible association between treatment outcome and a marker in HTR2A (P range 1 x 10(-6) to 3.7 x 10(-5) in the total sample). Other markers in HTR2A also showed evidence of association with treatment outcome in the total sample. HTR2A encodes the serotonin 2A receptor, which is downregulated by citalopram. Participants who were homozygous for the A allele had an 18% reduction in absolute risk of having no response to treatment, compared with those homozygous for the other allele. The A allele was over six times more frequent in white than in black participants, and treatment was less effective among black participants. The A allele may contribute to racial differences in outcomes of antidepressant treatment. Taken together with prior neurobiological findings, these new genetic data make a compelling case for a key role of HTR2A in the mechanism of antidepressant action.

Full Text

Duke Authors

Cited Authors

  • McMahon, FJ; Buervenich, S; Charney, D; Lipsky, R; Rush, AJ; Wilson, AF; Sorant, AJM; Papanicolaou, GJ; Laje, G; Fava, M; Trivedi, MH; Wisniewski, SR; Manji, H

Published Date

  • May 2006

Published In

Volume / Issue

  • 78 / 5

Start / End Page

  • 804 - 814

PubMed ID

  • 16642436

Pubmed Central ID

  • PMC1474035

International Standard Serial Number (ISSN)

  • 0002-9297

Digital Object Identifier (DOI)

  • 10.1086/503820

Language

  • eng

Conference Location

  • United States