ALDH2 gene: its effects on the neuropsychological functions in patients with opioid use disorder undergoing methadone maintenance treatment
Po-Wei Lee 1, Tzu-Yun Wang 1*, Yun-Hsuan Chang 2, Sheng-Yu Lee 3, Shiou-Lan Chen 4, Ze-Cheng Wang 5, 6, Po See Chen 1, 7, Chun-Hsien Chu 8, San-Yuan Huang 9, Nian-Sheng Tzeng 9, I Hui Lee 1, 7, Kao Chin Chen 1, 7, Yen Kuang Yang 1, 7, 10, Jau-Shyong Hong 11, Ru-Band Lu 1, 5, 12
1Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, 2Department of Psychology, Asia University, Taichung, Taiwan, 3Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, 4Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, 5The Affiliated Kangning Hospital of Wenzhou Medical University, Wenzhou City, China, 6Beijing YiNing Hospital, Beijing, China, 7Addiction Research Center, National Cheng Kung University, Tainan, Taiwan, 8Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan, 9Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, 10Department of Psychiatry, National Cheng Kung University Hospital, Dou-Liou Branch, Yunlin, Taiwan, 11Neurobiology Laboratory, NIH/NIEHS, Research Triangle Park, N.C., USA, 12Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli, Taiwan
Received: June 12, 2019; Revised: October 12, 2019; Accepted: October 14, 2019; Published online: October 14, 2019.
© The Korean College of Neuropsychopharmacology. All rights reserved.

Abstract
Aim: 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).
Methods: OUD patients undergoing methadone maintenance therapy (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.
Results: 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 (HRT) 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.
Conclusion: 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.
Keywords: aldehyde dehydrogenase 2, opioid use disorder, neuropsychological function, methadone maintenance therapy


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