Su Hang, Tao Jingyan, Zhang Jie, Xie Ying, Wang Yue, Zhang Yu, Han Bin, Lu Yuling, Sun Haiwei, Wei Youdan, Zou Shengzhen, Wu Wenxiu, Zhang Jiajia, Xu Ke, Zhang Xiangyang, He Jincai
From the *Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou; and †Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai, China; ‡Department of Psychiatry, Yale University, New Haven, CT; §Beijing Hui-Long-Guan Hospital, Peking University, Beijing, China; and ∥Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX.
J Clin Psychopharmacol. 2015 Oct;35(5):517-24. doi: 10.1097/JCP.0000000000000390.
Studies suggest that a functional polymorphism of the brain-derived neurotrophic factor gene (BDNF Val66Met) may contribute to methamphetamine dependence. We hypothesized that this polymorphism had a role in cognitive deficits in methamphetamine-dependent patients and in the relationship of serum BDNF with cognitive impairments. We conducted a case-control study by assessing 194 methamphetamine-dependent patients and 378 healthy volunteers without history of drug use on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the presence of the BDNF Val66Met polymorphism and serum BDNF levels. We showed no significant differences in genotype and allele distributions between the methamphetamine-dependent patients and controls. Some aspects of cognitive function significantly differed in the 2 groups. The serum BDNF levels in methamphetamine-dependent patients were significantly higher than those of the healthy controls. In the patients, partial correlation analysis showed a significant positive correlation between serum BDNF and the delayed memory index score. The RBANS scores showed statistically significant BDNF level × genotype interaction. Further regression analyses showed a significant positive association between BDNF levels and the RBANS total score, immediate memory or attention index among Val homozygote patients, whereas a significant negative association of BDNF levels with the RBANS total score, visuospatial/constructional, or language index was found among Met/Val heterozygous patients. We demonstrated significant impairment on some aspects of cognitive function and increased BDNF levels in methamphetamine-dependent patients as well as genotypic differences in the relationships between BDNF levels and RBANS scores on the BDNF Val66Met polymorphism only in these patients.
研究表明,脑源性神经营养因子基因的功能性多态性(BDNF Val66Met)可能与甲基苯丙胺依赖有关。我们推测这种多态性在甲基苯丙胺依赖患者的认知缺陷以及血清BDNF与认知障碍的关系中起作用。我们进行了一项病例对照研究,通过对194名甲基苯丙胺依赖患者和378名无吸毒史的健康志愿者进行神经心理状态重复评估量表(RBANS)测试,检测BDNF Val66Met多态性的存在情况以及血清BDNF水平。我们发现甲基苯丙胺依赖患者与对照组在基因型和等位基因分布上无显著差异。两组在认知功能的某些方面存在显著差异。甲基苯丙胺依赖患者的血清BDNF水平显著高于健康对照组。在患者中,偏相关分析显示血清BDNF与延迟记忆指数得分之间存在显著正相关。RBANS得分显示出BDNF水平×基因型的统计学显著交互作用。进一步的回归分析表明,在Val纯合子患者中,BDNF水平与RBANS总分、即时记忆或注意力指数之间存在显著正相关,而在Met/Val杂合子患者中,BDNF水平与RBANS总分、视觉空间/结构或语言指数之间存在显著负相关。我们证明了甲基苯丙胺依赖患者在认知功能的某些方面存在显著损害,BDNF水平升高,并且仅在这些患者中,BDNF Val66Met多态性在BDNF水平与RBANS得分之间的关系上存在基因型差异。