title: Influence of genetic polymorphisms involved in the hypothalamic-pituitary-adrenal axis and their interactions with environmental factors on antidepressant response.
abstract: OBJECTIVE
  To investigate the role of genetic polymorphisms in candidate genes associated with the HPA axis and their interactions with environmental stressors in antidepressant response.
  
  
  METHODS
  The remission of depressive symptoms after 8 weeks of antidepressant treatment was tested against 21 single nucleotide polymorphisms (SNPs) in five candidate genes associated with the HPA axis in a Chinese Han sample suffering from unipolar depression (n = 273). Any history of childhood trauma and recent negative life events were measured using the Childhood Trauma Questionnaire-Short Form (CTQ-SF) (n = 206) and the Life Event Scale (48 item, LES) (n = 207), respectively. Reporter gene assays were used to evaluate the possible effects of the most significant SNP on gene expression.
  
  
  RESULTS
  A functional polymorphism at 3'UTR of the corticotropin-releasing hormone receptor 1 (CRHR1) gene (rs28364032) and three haplotypes containing it showed significant relationships with antidepressant remission. Further laboratory-based genomic studies showed that the G-to-A change of rs28364032 resulted in a 10-12% decrease in the intensity of luciferase activity. However, we failed to find association of environments and their interaction with HPA system-related genes with antidepressant remission.
  
  
  CONCLUSIONS
  Our results support a definite role for CRHR1 in the pharmacogenetics of antidepressant drugs. This may contribute to interpatient differences in their responses to antidepressant drugs.
authors.affiliation: Neurologic Department of Affiliated ZhongDa Hospital, Neuropsychiatric Institute and Medical School of Southeast University, Nanjing, China.
authors.forename: Lei-Yu
authors.initials: LY
authors.lastname: Geng
authors.forename: Dong-Qing
authors.initials: DQ
authors.lastname: Ye
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Shi
authors.forename: Zhi
authors.initials: Z
authors.lastname: Xu
authors.forename: Meng-Jia
authors.initials: MJ
authors.lastname: Pu
authors.forename: Zan-Yuan
authors.initials: ZY
authors.lastname: Li
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Li
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Zhi-Jun
authors.initials: ZJ
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D044466:Asian People / Q000208:ethnology; D002461:Cell Line, Transformed; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D004777:Environment; D005260:Female; D059647:Gene-Environment Interaction; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D000099052:CRF Receptor, Type 1
chemical_list: D000928:Antidepressive Agents; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D049452:Green Fluorescent Proteins; D000099052:CRF Receptor, Type 1
keywords: Antidepressant response; CRHR1; Environmental factors; HPA