ALDH2 polymorphism, associated with attenuating negative symptoms in patients with schizophrenia treated with add-on dextromethorphan.

Abstract

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.

• Authors: Sheng-Yu Lee, Shiou-Lan Chen, Yun-Hsuan Chang, Po-See Chen, San-Yuan Huang, Nian-Sheng Tzeng, Liang-Jen Wang, I-Hui Lee, Tzu-Yun Wang, Kao-Chin Chen, Yen-Kuang Yang, Jau-Shyong Hong, Ru-Band Lu
• Journal: Journal of psychiatric research (J Psychiatr Res) Vol. 69 Pg. 50-6 (Oct 2015) ISSN: 1879-1379 [Electronic] England
• PMID: 26343594 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• Antipsychotic Agents
• Excitatory Amino Acid Antagonists
• Neuroprotective Agents
• Dextromethorphan
• ALDH2 protein, human
• Aldehyde Dehydrogenase
• Aldehyde Dehydrogenase, Mitochondrial
• Risperidone

Topics

• Adult
• Aldehyde Dehydrogenase (genetics)
• Aldehyde Dehydrogenase, Mitochondrial
• Antipsychotic Agents (therapeutic use)
• Dextromethorphan (therapeutic use)
• Double-Blind Method
• Drug Therapy, Combination
• Excitatory Amino Acid Antagonists (therapeutic use)
• Female
• Genotyping Techniques
• Humans
• Male
• Neuroprotective Agents (therapeutic use)
• Polymerase Chain Reaction
• Polymorphism, Genetic
• Psychiatric Status Rating Scales
• Risperidone (therapeutic use)
• Schizophrenia (drug therapy, genetics)
• Schizophrenic Psychology
• Time Factors
• Treatment Outcome