ALDH2 polymorphism, associated with attenuating negative symptoms in patients with schizophrenia treated with add-on dextromethorphan.
OBJECTIVE
Increasing the evidence of inflammation's contribution to schizophrenia; using anti-inflammatory or neurotrophic therapeutic agents to see whether they improve schizophrenia treatment. Dextromethorphan (DM), a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, might protect monoamine neurons. Whether treating schizophrenia with risperidone plus add-on DM is more effective than risperidone (RISP) alone, and the association between the ALDH2 polymorphism and treatment response were investigated.


METHODS
A double-blind study in which patients with schizophrenia were randomly assigned to the RISP + DM (60 mg/day; n = 74) or the RISP + Placebo (n = 75) group. The Positive and Negative Syndrome Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS) scores were used to evaluate clinical response during weeks 0, 1, 2, 4, 6, 8, and 11. The genotypes of the ALDH2 polymorphism were determined using polymerase chain reactions plus restriction fragment length polymorphism analysis. A generalized estimating equation was used to analyze the effects of ALDH2 polymorphism on the clinical performance of DM.


RESULTS
PANSS and SANS scores were significantly lower in both groups after 11 weeks of treatment. SANS total scores were significantly lower in the RISP + DM group in patients with the ALDH2*2*2 genotype.


CONCLUSIONS
RISP plus add-on DM treatment reduced negative schizophrenia symptoms in patients with the ALDH2 polymorphism.
Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Department of Psychiatry, College of Medicine and Hospital, National Cheng Kung University, Tainan, Taiwan.
Sheng-Yu
SY
Lee
Department of Psychiatry, College of Medicine and Hospital, National Cheng Kung University, Tainan, Taiwan; Department of Neurology, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Shiou-Lan
SL
Chen
Department of Psychiatry, College of Medicine and Hospital, National Cheng Kung University, Tainan, Taiwan; Institute of Allied Health Sciences, College of Medicine and Hospital, National Cheng Kung University, Tainan, Taiwan; Deprtment of Psychology, Asia University, Taichung, Taiwan.
Yun-Hsuan
YH
Chang
Department of Psychiatry, College of Medicine and Hospital, National Cheng Kung University, Tainan, Taiwan; Addiction Research Center, National Cheng Kung University, Tainan, Taiwan; Department of Psychiatry, National Cheng Kung University Hospital, Tainan, Taiwan.
Po-See
PS
Chen
Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
San-Yuan
SY
Huang
Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Nian-Sheng
NS
Tzeng
Department of Child and Adolescent Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Liang-Jen
LJ
Wang
Department of Psychiatry, College of Medicine and Hospital, National Cheng Kung University, Tainan, Taiwan; Department of Psychiatry, National Cheng Kung University Hospital, Tainan, Taiwan; Department of Psychiatry, National Cheng Kung University Hospital, Dou-Liou Branch, Yunlin, Taiwan.
I-Hui
IH
Lee
Department of Psychiatry, College of Medicine and Hospital, National Cheng Kung University, Tainan, Taiwan; Department of Psychiatry, National Cheng Kung University Hospital, Tainan, Taiwan.
Tzu-Yun
TY
Wang
Department of Psychiatry, College of Medicine and Hospital, National Cheng Kung University, Tainan, Taiwan; Department of Psychiatry, National Cheng Kung University Hospital, Tainan, Taiwan.
Kao-Chin
KC
Chen
Department of Psychiatry, College of Medicine and Hospital, National Cheng Kung University, Tainan, Taiwan; Institute of Behavioral Medicine, College of Medicine and Hospital, National Cheng Kung University, Tainan, Taiwan; Addiction Research Center, National Cheng Kung University, Tainan, Taiwan; Department of Psychiatry, National Cheng Kung University Hospital, Tainan, Taiwan.
Yen-Kuang
YK
Yang
Laboratory of Neurobiology, NIH/NIEHS, Research Triangle Park, NC, USA.
Jau-Shyong
JS
Hong
Department of Psychiatry, College of Medicine and Hospital, National Cheng Kung University, Tainan, Taiwan; Institute of Behavioral Medicine, College of Medicine and Hospital, National Cheng Kung University, Tainan, Taiwan; Institute of Allied Health Sciences, College of Medicine and Hospital, National Cheng Kung University, Tainan, Taiwan; Addiction Research Center, National Cheng Kung University, Tainan, Taiwan; Department of Psychiatry, National Cheng Kung University Hospital, Tainan, Taiwan; Center for Neuropsychiatric Research, National Health Research Institutes, Taiwan. Electronic address: rblu@mail.ncku.edu.tw.
Ru-Band
RB
Lu
D000328:Adult; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D003915:Dextromethorphan / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use; D005260:Female; D060005:Genotyping Techniques; D006801:Humans; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011569:Psychiatric Status Rating Scales; D018967:Risperidone / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics; D012565:Schizophrenic Psychology; D013997:Time Factors; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D003915:Dextromethorphan; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D018967:Risperidone
ALDH2 polymorphism; Dextromethorphan; Schizophrenia