Clin Psychopharmacol Neurosci.  2020 Feb;18(1):136-144. 10.9758/cpn.2020.18.1.136.

ALDH2 Gene: Its Effects on the Neuropsychological Functions in Patients with Opioid Use Disorder Undergoing Methadone Maintenance Treatment

  • 1Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan
  • 2Department of Psychology, Asia University
  • 3Department of Medical Research, China Medical University Hospital, China Medical University, Taichung
  • 4Department of Psychiatry, Kaohsiung Veterans General Hospital
  • 5Graduate Institute of Medicine, College of Medicine
  • 6Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
  • 7The Affiliated Kangning Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang
  • 8Beijing YiNing Hospital, Beijing, China
  • 9Addiction Research Center, National Cheng Kung University
  • 10Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan
  • 11Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center
  • 12Student Counseling Center, National Defense Medical Center, Taipei
  • 13Department of Psychiatry, National Cheng Kung University Hospital, Dou-Liou Branch, Yunlin, Taiwan
  • 14Neurobiology Laboratory, NIH/NIEHS, Research Triangle Park, NC, USA


Patients with opioid use disorder (OUD) have impaired attention, inhibition control, and memory function. The aldehyde dehydrogenase 2 (ALDH2 ) gene has been associated with OUD and ALDH2 gene polymorphisms may affect aldehyde metabolism and cognitive function in other substance use disorder. Therefore, we aimed to investigate whether ALDH2 genotypes have significant effects on neuropsychological functions in OUD patients undergoing methadone maintenance therapy (MMT).
OUD patients undergoing MMT were investigated and followed-up for 12 weeks. ALDH2 gene polymorphisms were genotyped. Connors’ Continuous Performance Test (CPT) and the Wechsler Memory Scale-Revised (WMS-R) were administered at baseline and after 12 weeks of MMT. Multivariate linear regressions and generalized estimating equations (GEEs) were used to examine the correlation between the ALDH2 genotypes and performance on the CPTs and WMS-R.
We enrolled 86 patients at baseline; 61 patients completed the end-of-study assessments. The GEE analysis showed that, after the 12 weeks of MMT, OUD patients with the ALDH2 *1/*2+*2/*2 (ALDH2 inactive) genotypes had significantly higher commission error T-scores (p = 0.03), significantly lower hit reaction time T-scores (p = 0.04), and significantly lower WMS-R visual memory index scores (p = 0.03) than did patients with the ALDH2 1 */*1 (ALDH2 active) genotype.
OUD patients with the ALDH2 inactive genotypes performed worse in cognitive domains of attention, impulse control, and memory than did those with the ALDH2 active genotype. We conclude that the ALDH2 gene is important in OUD and is associated with neuropsychological performance after MMT.


Aldehyde dehydrogenase; Opioid-related disorders; Cognition; Methadone
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