Tzu-Yun Wang1, Sheng-Yu Lee2, Yun-Hsuan Chang3, Shiou-Lan Chen4, Po See Chen5, Chun-Hsien Chu6, San-Yuan Huang7, Nian-Sheng Tzeng8, I Hui Lee9, Kao Chin Chen9, Yen Kuang Yang10, Shih-Heng Chen11, Jau-Shyong Hong11, Ru-Band Lu12. 1. Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 70428, Taiwan; Department of Psychiatry, National Cheng Kung University Hospital, Dou-Liou Branch, No. 345, Zhuangjing Road, Douliu, Yunlin 64043, Taiwan. Electronic address: n622498@mail.hosp.ncku.edu.tw. 2. Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 70428, Taiwan; Department of Psychiatry, Kaohsiung Veterans General Hospital, No. 386, Dazhong 1st Road, Zuoying Dist., Kaohsiung 81362, Taiwan. 3. Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 70428, Taiwan; Department of Psychology, Asia University, 500, Lioufeng Road, Wufeng, Taichung 41354, Taiwan; Department of Medical Research, China Medical University Hospital, China Medical University, No. 91, Hsueh-Shih Road, Taichung 40402, Taiwan. 4. Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 70428, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, 100, Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan; Lipid Science and Aging Research Center, Kaohsiung Medical University, 100, Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan. 5. Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 70428, Taiwan; Institute of Behavioral Medicine, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 70428, Taiwan. 6. Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, 3F, No. 367, Sheng-Li Rd., North District, Tainan 70456, Taiwan. 7. Department of Psychiatry, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, No. 325, Sec. 2, Chenggong Road., Neihu District, Taipei 11490, Taiwan. 8. Department of Psychiatry, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, No. 325, Sec. 2, Chenggong Road., Neihu District, Taipei 11490, Taiwan; Student Counseling Center, National Defense Medical Center, No.161, Sec. 6, Minquan E. Road., Neihu Dist., Taipei 11490, Taipei, Taiwan. 9. Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 70428, Taiwan. 10. Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 70428, Taiwan; Department of Psychiatry, National Cheng Kung University Hospital, Dou-Liou Branch, No. 345, Zhuangjing Road, Douliu, Yunlin 64043, Taiwan; Institute of Behavioral Medicine, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 70428, Taiwan. 11. Neurobiology Laboratory, NIEHS/NIH, Research Triangle Park, 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, USA. 12. Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 70428, Taiwan; Institute of Behavioral Medicine, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 70428, Taiwan; Beijing YiNing Hospital, No. 9 Minzhuang Road, Haidian District, Beijing 100195, China; Center for Neuropsychiatric Research, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 35053, Taiwan.
Abstract
BACKGROUND: Patients with opioid use disorder (OUD) show memory deficiencies and impaired treatment outcomes. Emerging evidence suggests that opioid abuse activates proinflammatory processes by increasing cytokine production and impairing neuroprotection, which damages the memory function in OUD patients. Therefore, we investigated whether plasma-based inflammatory and neurotrophic markers correlate with memory function in OUD patients. METHOD: OUD patients undergoing methadone maintenance therapy (MMT) were investigated and followed up for 12 weeks. Plasma tumor necrosis factor (TNF)-α, C-reactive protein (CRP), interleukin (IL)-6, transforming growth factor (TGF)-β1, brain-derived neurotrophic factor (BDNF) levels, and Wechsler Memory Scale-Revised (WMS-R) scores were assessed at baseline and after 12 weeks of MMT. Multiple linear regressions and generalized estimating equations (GEEs) were used to examine the correlation between cytokines and memory performance. RESULTS: We enrolled 89 patients at baseline; 47 patients completed the end-of-study assessments. Although Pearson correlations showed that CRP and TGF-β1 levels were significantly, negatively associated with some memory indices, the results were not significant after correction. The GEE results, controlled for several confounding factors and multiple testing, showed that changes in TNF-α levels were negatively correlated with changes in the visual memory index (P = 0.01), and that changes in IL-6 levels were negatively correlated with changes in the verbal memory index (P = 0.009). CONCLUSION: Memory performance, TNF-α, and IL-6 levels in OUD patients were negative correlated. Additional studies on regulating TNF-α and IL-6 expression to improve memory function in OUD patients might be warranted.
BACKGROUND:Patients with opioid use disorder (OUD) show memory deficiencies and impaired treatment outcomes. Emerging evidence suggests that opioid abuse activates proinflammatory processes by increasing cytokine production and impairing neuroprotection, which damages the memory function in OUD patients. Therefore, we investigated whether plasma-based inflammatory and neurotrophic markers correlate with memory function in OUD patients. METHOD: OUD patients undergoing methadone maintenance therapy (MMT) were investigated and followed up for 12 weeks. Plasma tumor necrosis factor (TNF)-α, C-reactive protein (CRP), interleukin (IL)-6, transforming growth factor (TGF)-β1, brain-derived neurotrophic factor (BDNF) levels, and Wechsler Memory Scale-Revised (WMS-R) scores were assessed at baseline and after 12 weeks of MMT. Multiple linear regressions and generalized estimating equations (GEEs) were used to examine the correlation between cytokines and memory performance. RESULTS: We enrolled 89 patients at baseline; 47 patients completed the end-of-study assessments. Although Pearson correlations showed that CRP and TGF-β1 levels were significantly, negatively associated with some memory indices, the results were not significant after correction. The GEE results, controlled for several confounding factors and multiple testing, showed that changes in TNF-α levels were negatively correlated with changes in the visual memory index (P = 0.01), and that changes in IL-6 levels were negatively correlated with changes in the verbal memory index (P = 0.009). CONCLUSION: Memory performance, TNF-α, and IL-6 levels in OUD patients were negative correlated. Additional studies on regulating TNF-α and IL-6 expression to improve memory function in OUD patients might be warranted.
Authors: Magdalena Kurnik-Łucka; Gniewomir Latacz; Adrian Martyniak; Andrzej Bugajski; Katarzyna Kieć-Kononowicz; Krzysztof Gil Journal: Neurotox Res Date: 2019-11-15 Impact factor: 3.911