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 Nemeroff

Research output: Contribution to journalArticle

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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
Pages (from-to)369-379
Number of pages11
JournalArchives of General Psychiatry
Volume67
Issue number4
DOIs
StatePublished - Apr 1 2010

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Citalopram
Corticotropin-Releasing Hormone
Antidepressive Agents
Depression
Genes
Arginine Vasopressin
Hispanic Americans
African Americans
Adrenocorticotropic Hormone
Single Nucleotide Polymorphism
Therapeutics
Alleles
Major Depressive Disorder
Genetic Association Studies
Genetic Polymorphisms
Depressive Disorder
Ambulatory Care
Anxiety Disorders
Gene Frequency
Dexamethasone

ASJC Scopus subject areas

  • Psychiatry and Mental health

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Association of polymorphisms in genes regulating the corticotropin- releasing factor system with antidepressant treatment response. / Binder, Elisabeth B.; Owens, Michael J.; Liu, Wei; Deveau, Todd C.; Rush, A. John; Trivedi, Madhukar H.; Fava, Maurizio; Bradley, Bekh; Ressler, Kerry J.; Nemeroff, Charles.

In: Archives of General Psychiatry, Vol. 67, No. 4, 01.04.2010, p. 369-379.

Research output: Contribution to journalArticle

Binder, Elisabeth B. ; Owens, Michael J. ; Liu, Wei ; Deveau, Todd C. ; Rush, A. John ; Trivedi, Madhukar H. ; Fava, Maurizio ; Bradley, Bekh ; Ressler, Kerry J. ; Nemeroff, Charles. / Association of polymorphisms in genes regulating the corticotropin- releasing factor system with antidepressant treatment response. In: Archives of General Psychiatry. 2010 ; Vol. 67, No. 4. pp. 369-379.
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