The DRD2/ANKK1 gene is associated with response to add-on dextromethorphan treatment in bipolar disorder.
Dextromethorphan (DM) is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist that may be neuroprotective for monoamine neurons. We hypothesized that adding DM to valproate (VPA) treatment would attenuate bipolar disorder (BP) symptoms. We evaluated in BP patients the association between the DRD2/ANKK1 TaqIA polymorphism with treatment response to VPA+add-on DM and to VPA+placebo. This double-blind, stratified, randomized study ran from January 2007 through December 2010. BP patients undergoing regular VPA treatments were randomly assigned to groups given either add-on DM (60 mg/day) (n=167) or placebo (n=83) for 12 weeks. The Young Mania Rating Scale (YMRS) and Hamilton Depression Rating Scale (HDRS) were used to evaluate clinical response. The genotypes of the DRD2/ANKK1 TaqIA polymorphisms were determined using polymerase chain reactions plus restriction fragment length polymorphism analysis. To adjust within-subject dependence over repeated assessments, multiple linear regression with generalized estimating equation methods was used to analyze the effects of the DRD2/ANKK1 TaqIA polymorphism on clinical performance. Both groups showed significantly decreased YMRS and HDRS scores after 12 weeks of treatment; the differences between groups were non-significant. Decreases in YMRS scores were greater in patients with the A1A1 (P=0.004) genotypes than with the A2A2 genotype. We conclude that the DRD2/ANKK1 TaqIA polymorphism influenced responses to DM by decreasing manic symptoms in BP patients.
Department of Psychiatry, College of Medicine and Hospital, National Cheng Kung University, Tainan, Taiwan.
Sheng-Yu
SY
Lee
Shiou-Lan
SL
Chen
Yun-Hsuan
YH
Chang
Shih-Heng
SH
Chen
Chun-Hsieh
CH
Chu
San-Yuan
SY
Huang
Nian-Sheng
NS
Tzeng
Chen-Lin
CL
Wang
I Hui
IH
Lee
Tzung Lieh
TL
Yeh
Yen Kuang
YK
Yang
Ru-Band
RB
Lu
D000328:Adult; D018692:Antimanic Agents / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000235:genetics*; D003915:Dextromethorphan / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D014635:Valproic Acid / Q000627:therapeutic use; D055815:Young Adult
D018692:Antimanic Agents; D018696:Neuroprotective Agents; D017448:Receptors, Dopamine D2; D016194:Receptors, N-Methyl-D-Aspartate; D014635:Valproic Acid; D003915:Dextromethorphan; C489948:ANKK1 protein, human; D017346:Protein Serine-Threonine Kinases