Analysis of Association Between the Serotonin Transporter and Antidepressant Response in a Large Clinical Sample

Jeffrey B. Kraft, Eric J. Peters, Susan L. Slager, Greg D. Jenkins, Megan S. Reinalda, Patrick J. McGrath, Steven P. Hamilton

Research output: Contribution to journalArticle

142 Scopus citations

Abstract

Background: SLC6A4 encodes the serotonin transporter, the protein primarily responsible for the termination of serotonin neurotransmission. Because many antidepressants inhibit the transporter, it has been the focus of intense pharmacogenetic analysis. We sought to replicate our previous findings that SLC6A4 is associated with response to a selective serotonin reuptake inhibitor (SSRI) in a large case-control study. Methods: Genotypes at the SLC6A4 locus were obtained for 1,914 subjects in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study and then tested for association to treatment response of the SSRI citalopram. Results: Nine tagging single nucleotide polymorphisms and two variants previously associated with antidepressant response, including a promoter repeat polymorphism, were genotyped. Single marker and haplotypic analyses failed to detect association with antidepressant response in the largest clinical sample studied to date. Conclusions: The lack of association between response to an SSRI and variation at the SLC6A4 locus in this large sample, carefully characterized for response to citalopram, strongly suggests that SSRI response in major depression is not determined by DNA variation at this locus. These findings do not replicate findings of a number of studies with considerably smaller sample sizes. Other genetic determinants of SSRI response in depression should be sought.

Original languageEnglish (US)
Pages (from-to)734-742
Number of pages9
JournalBiological psychiatry
Volume61
Issue number6
DOIs
StatePublished - Mar 15 2007

Keywords

  • 5-HTTLPR
  • Association
  • SLC6A4
  • SNP
  • STAR*D
  • case-control
  • citalopram
  • pharmacogenetics

ASJC Scopus subject areas

  • Biological Psychiatry

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