Association of polymorphisms in genes regulating the corticotropin- releasing factor system with antidepressant treatment response

Elisabeth B. Binder, Michael J. Owens, Wei Liu, Todd C. Deveau, A. John Rush, Madhukar H. Trivedi, Maurizio Fava, Bekh Bradley, Kerry J. Ressler, Charles B. Nemeroff

Research output: Contribution to journalArticle

85 Scopus citations

Abstract

Context: The corticotropin-releasing factor (CRF, or corticotropin- releasing hormone) and arginine vasopressin systems have been implicated in the pathophysiology of anxiety and depressive disorders and response to antidepressant treatment. Objective: To study the association of genetic variants in 10 genes that regulate the CRF and arginine vasopressin systems with treatment response to Citalopram in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) sample (N= 1768). Design: Pharmacogenetic association study derived from the STAR*D study, a multieenter, prospective, open, 12-week effectiveness trial. Setting: Outpatient primary care and psychiatric clinics. Patients: Individuals with nonpsychotic major depressive disorder for whom DNA was available who were subsequently treated with Citalopram hydrobromide for 4 to 12 weeks. Intervention: Flexible doses of Citalopram. Main Outcome Measure: Association of genetic polymorphisms in genes encoding the CRF system with response and remission to Citalopram treatment at exit visit. Results: One single-nucleotide polymorphism (SNP) (rsl0473984) within the CRHBP locus showed a significant association with both remission (P=6.0 X 10 -6; corrected, P=. 0026) and reduction in depressive symptoms (P= 7.0 X 10 -7; corrected, P=.00031) in response to Citalopram. The T allele of this SNP was associated with poorer treatment outcome in 2 of the 3 ethnic subsamples (African American and Hispanic), despite large differences in minor allele frequency. This association was more pronounced in patients with features of anxious depression (P= .008). The nonresponse allele was shown to be associated with overall higher plasma corticotropin levels and more pronounced dexamethasone suppression of corticotropin. Conclusions: These data indicate that a genetic variant within the CRHBP locus affects response to Citalopram in African American and Hispanic patients, suggesting a role for this gene and for the CRF system in antidepressant treatment response.

Original languageEnglish (US)
Pages (from-to)369-379
Number of pages11
JournalArchives of General Psychiatry
Volume67
Issue number4
DOIs
StatePublished - Apr 2010

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Psychiatry and Mental health

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