title: Harm avoidance involved in mediating the association between nerve growth factor (NGF) gene polymorphisms and antidepressant efficacy in patients with major depressive disorder.
abstract: BACKGROUND
  Antidepressants have variable efficacies in subjects with major depressive disorder (MDD). Nerve growth factor (NGF) has been suggested to play an important role in the pathogenesis of depressive symptoms and the response to antidepressant therapy. The aim of this study was to examine whether NGF gene polymorphisms are associated with the antidepressant therapeutic efficacy in subjects with MDD.
  
  
  METHODS
  A naturalistic follow-up study was carried out on 557 subjects with MDD. Of the enrolled patients, 304 completed the 8-week open-label antidepressant treatment. Seven single-nucleotide polymorphisms (SNPs) of the NGF gene were genotyped. The 21-item Hamilton Depression Rating Scale was used to assess depressive severity from baseline to endpoint. Tridimensional Personality Questionnaire was used to assess baseline personality traits. Single marker and haplotype analyses were conducted. Binary logistic regression was used to calculate odds ratios of remission. Structural equation modeling was used to analyze the predicted mediation effect.
  
  
  RESULTS
  A significant difference in genotype frequencies between remitters and non-remitters was observed in three NGF SNPs (rs12760036, rs7523654, and rs17033692). The haplotype analysis revealed that the CCC haplotype (rs2254527-rs6678788-rs12760036) was associated with a higher remission rate, while the CCA haplotype was associated with a lower remission rate. The harm avoidance psychological factor partially mediated the effect of NGF variants on antidepressant efficacy.
  
  
  CONCLUSIONS
  The selected SNPs may not cover whole NGF gene.
  
  
  CONCLUSIONS
  NGF variants are associated with remission rates after 8-week antidepressant treatment, and harm avoidance partially mediated the effect of NGF variants on treatment outcomes.
authors.affiliation: Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Department of Psychiatry, Keelung Branch, Tri-Service General Hospital, Keelung, Taiwan.
authors.forename: Yi-Wei
authors.initials: YW
authors.lastname: Yeh
authors.affiliation: Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Department of Psychiatry, Keelung Branch, Tri-Service General Hospital, Keelung, Taiwan; Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Shin-Chang
authors.initials: SC
authors.lastname: Kuo
authors.affiliation: Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Chun-Yen
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan; Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Chih-Sung
authors.initials: CS
authors.lastname: Liang
authors.affiliation: Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Pei-Shen
authors.initials: PS
authors.lastname: Ho
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan; Department of Neurology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Che-Hung
authors.initials: CH
authors.lastname: Yen
authors.affiliation: Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Tien-Yu
authors.initials: TY
authors.lastname: Chen
authors.affiliation: Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Department of Biology & Anatomy, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Jia-Fwu
authors.initials: JF
authors.lastname: Shyu
authors.affiliation: Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Fang-Jung
authors.initials: FJ
authors.lastname: Wan
authors.affiliation: Institute of Behavioral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Ru-Band
authors.initials: RB
authors.lastname: Lu
authors.affiliation: Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan. Electronic address: hsy@ndmctsgh.edu.tw.
authors.forename: San-Yuan
authors.initials: SY
authors.lastname: Huang
mesh_terms: D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006239:Haplotypes; D040261:Harm Reduction; D006801:Humans; D008297:Male; D008875:Middle Aged; D020932:Nerve Growth Factor / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; C502240:NGF protein, human; D020932:Nerve Growth Factor
keywords: Antidepressant; Harm avoidance; Major depressive disorder; NGF gene; Remission