title: The COMT Val158Met Polymorphism Is Associated With Response to Add-on Dextromethorphan Treatment in Bipolar Disorder.
abstract: OBJECTIVE
  We previously conducted a randomized, double-blind, controlled, 12-week study evaluating the effect of add-on dextromethorphan (DM), a noncompetitive N-methyl-D-aspartate receptor antagonist, on patients with bipolar disorder (BD) treated using valproate (VPA), which showed negative clinical differences. The genetic variation between each individual may be responsible for interindividual differences. The catechol-O-methyltransferase (COMT) gene has been a candidate gene for BD. In the current study, we investigated whether the COMT Val158Met polymorphism predicts treatment response to VPA + add-on DM and to VPA + placebo.
  
  
  METHODS
  Patients with BD (n = 309) undergoing regular VPA treatments were randomly assigned to groups given either add-on DM (30 mg/d) (n = 102), DM (60 mg/d) (n = 101), or placebo (n = 106) for 12 weeks. The Hamilton Depression Rating Scale and Young Mania Rating Scale were used to evaluate clinical response during weeks 0, 1, 2, 4, 8, and 12. The genotypes of the COMT Val158Met polymorphism were determined using polymerase chain reaction plus restriction fragment length polymorphism analysis. To adjust for within-subject dependence over repeated assessments, multiple linear regression with generalized estimating equation methods was used.
  
  
  RESULTS
  When stratified by the COMT Val158Met genotypes, significantly greater decreases in Hamilton Depression Rating Scale scores were found in the VPA + DM (30 mg/d) group in patients with the Val/Met genotype (P = 0.008).
  
  
  CONCLUSIONS
  We conclude that the COMT Val158Met polymorphism may influence responses to DM (30 mg/d) by decreasing depressive symptoms in BD patients.
authors.affiliation: From the *Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung; †Department of Psychiatry, National Cheng Kung University, Tainan; ‡Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University (KMU), Lipid Science and Aging Research Center, KMU, Kaohsiung; §Institute of Allied Health Sciences, College of Medicine and Hospital, National Cheng Kung University, Tainan; ∥Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei; ¶Department of Child and Adolescent Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung; #Institute of Behavioral Medicine and **Addiction Research Center, National Cheng Kung University, Tainan; ††Department of Psychiatry, National Cheng Kung University Hospital, Dou-Liou Branch, Yunlin; and ‡‡Center for Neuropsychiatric Research, National Health Research Institute, Zhunan, Miaoli County, Taiwan.
authors.forename: Sheng-Yu
authors.initials: SY
authors.lastname: Lee
authors.forename: Shiou-Lan
authors.initials: SL
authors.lastname: Chen
authors.forename: Tzu-Yun
authors.initials: TY
authors.lastname: Wang
authors.forename: Yun-Hsuan
authors.initials: YH
authors.lastname: Chang
authors.forename: Po See
authors.initials: PS
authors.lastname: Chen
authors.forename: San-Yuan
authors.initials: SY
authors.lastname: Huang
authors.forename: Nian-Sheng
authors.initials: NS
authors.lastname: Tzeng
authors.forename: Liang-Jen
authors.initials: LJ
authors.lastname: Wang
authors.forename: I Hui
authors.initials: IH
authors.lastname: Lee
authors.forename: Kao Ching
authors.initials: KC
authors.lastname: Chen
authors.forename: Yen Kuang
authors.initials: YK
authors.lastname: Yang
authors.forename: Ru-Band
authors.initials: RB
authors.lastname: Lu
mesh_terms: D018692:Antimanic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003915:Dextromethorphan / Q000008:administration & dosage / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D017063:Outcome Assessment, Health Care; D014635:Valproic Acid / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D018692:Antimanic Agents; D018691:Excitatory Amino Acid Antagonists; D014635:Valproic Acid; D003915:Dextromethorphan; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase