Association study of corticotropin-releasing hormone receptor1 gene polymorphisms and antidepressant response in major depressive disorders

Neurosci Lett. 2007 Mar 6;414(2):155-8. doi: 10.1016/j.neulet.2006.12.013. Epub 2006 Dec 15.

Abstract

Hypothalamic-pituitary-adrenal (HPA) axis appears to play a key role in the pathogenesis of major depressive disorders (MDD). Treatment of certain selective serotonin reuptake inhibitors (SSRIs) has been shown to reduce the activity of corticotropin-releasing hormone (CRH) neurons and may contribute to their therapeutic action. It has been proposed that the downregulation of CRH activity is final and common step of antidepressant treatment. In this study, we tested whether the polymorphisms of three sites (rs1876828, rs242939 and rs242941) in corticotropin-releasing hormone receptor1 (CRHR1) gene are related to 6 weeks fluoxetine antidepressant effect in 127 Han Chinese patients with MDD. The results show that the rs242941 G/G genotype and homozygous GAG haplotype of the three single-nucleotide polymorphisms (SNPs) are associated with fluoxetine therapeutic response in MDD patients of high-anxiety (HA). The results support the idea that the CRHR1 gene is likely to be involved in the antidepressant response in MDD.

MeSH terms

  • Adult
  • Antidepressive Agents / pharmacology
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / physiopathology
  • China
  • Corticotropin-Releasing Hormone / metabolism
  • DNA Mutational Analysis
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / genetics*
  • Depressive Disorder, Major / metabolism
  • Drug Resistance / genetics*
  • Female
  • Fluoxetine / pharmacology
  • Genetic Markers / genetics
  • Genetic Predisposition to Disease / genetics
  • Genetic Testing
  • Heterozygote
  • Homozygote
  • Humans
  • Hypothalamo-Hypophyseal System / drug effects
  • Hypothalamo-Hypophyseal System / metabolism
  • Hypothalamo-Hypophyseal System / physiopathology
  • Male
  • Pituitary-Adrenal System / drug effects
  • Pituitary-Adrenal System / metabolism
  • Pituitary-Adrenal System / physiopathology
  • Polymorphism, Genetic / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Receptors, Corticotropin-Releasing Hormone / genetics*
  • Selective Serotonin Reuptake Inhibitors / pharmacology

Substances

  • Antidepressive Agents
  • Genetic Markers
  • Receptors, Corticotropin-Releasing Hormone
  • Serotonin Uptake Inhibitors
  • Fluoxetine
  • CRF receptor type 1
  • Corticotropin-Releasing Hormone