Center for Imaging of Neurodegenerative Diseases, San Francisco VA Medical Center San Francisco, CA, USA ; Department of Radiology and Biomedical Imaging, University of California San Francisco, CA, USA.
Front Pharmacol. 2012 Oct 11;3:178. doi: 10.3389/fphar.2012.00178. eCollection 2012.
Chronic cigarette smoking and polymorphisms in brain-derived neurotrophic factor (BDNF) and catechol-O-methyltransferase (COMT) are associated with neurocognition in normal controls and those with various neuropsychiatric conditions. The influence of BDNF and COMT on neurocognition in alcohol dependence is unclear. The primary goal of this report was to investigate the associations of single nucleotide polymorphisms (SNPs) in BDNF Val66Met (rs6265) and COMT Val158Met (rs4680) with neurocognition in a treatment-seeking alcohol dependent cohort and determine if neurocognitive differences between non-smokers and smokers previously observed in this cohort persist when controlled for these functional SNPs. Genotyping was conducted on 70 primarily male treatment-seeking alcohol dependent participants (ALC) who completed a comprehensive neuropsychological battery after 33 ± 9 days of monitored abstinence. After controlling for COMT and BDNF genotypes, smoking ALC performed significantly worse than non-smoking ALC on the domains of auditory-verbal and visuospatial learning and memory, cognitive efficiency, general intelligence, processing speed, and global neurocognition. In smoking ALC, greater number of years of smoking over lifetime was related to poorer performance on multiple domains after controlling for genotypes and alcohol consumption. In addition, COMT Met homozygotes were superior to Val homozygotes on measures of executive skills and showed trends for higher general intelligence and visuospatial skills, while COMT Val/Met heterozygotes showed significantly better general intelligence than Val homozygotes. COMT Val homozygotes performed better than heterozygotes on auditory-verbal memory. BDNF genotype was not related to any neurocognitive domain. The findings are consistent with studies in normal controls and neuropsychiatric cohorts that reported COMT Met carriers demonstrated better performance on measures of executive skills and general intelligence. Results also indicated that the poorer performance of smoking compared to non-smoking ALC across multiple neurocognitive domains was not mediated by COMT or BDNF genotype. Overall, the findings lend support to the expanding clinical movement to make smoking cessation programs available to smokers at the inception of treatment for alcohol/substance use disorders.
慢性吸烟和脑源性神经营养因子（BDNF）和儿茶酚-O-甲基转移酶（COMT）的多态性与正常对照者和各种神经精神疾病患者的神经认知有关。BDNF 和 COMT 对酒精依赖的神经认知的影响尚不清楚。本报告的主要目的是研究治疗性饮酒依赖队列中 BDNF Val66Met（rs6265）和 COMT Val158Met（rs4680）单核苷酸多态性（SNP）与神经认知的相关性，并确定在控制这些功能性 SNP 后，先前在该队列中观察到的非吸烟者和吸烟者之间的神经认知差异是否仍然存在。对 70 名主要为男性的治疗性酒精依赖参与者（ALC）进行基因分型，这些参与者在经过 33 ± 9 天的监测禁欲后完成了全面的神经心理测试。在控制 COMT 和 BDNF 基因型后，吸烟的 ALC 在听觉语言和视觉空间学习和记忆、认知效率、一般智力、处理速度和整体神经认知等领域的表现明显差于非吸烟的 ALC。在吸烟的 ALC 中，在控制基因型和酒精摄入量后，终生吸烟的年数与多个领域的表现较差相关。此外，COMT Met 纯合子在执行技能方面优于 Val 纯合子，并且有更高的一般智力和空间技能的趋势，而 COMT Val/Met 杂合子的一般智力明显优于 Val 纯合子。COMT Val 纯合子在听觉语言记忆方面的表现优于杂合子。BDNF 基因型与任何神经认知领域均无关。这些发现与正常对照组和神经精神病队列的研究一致，这些研究报告称 COMT Met 携带者在执行技能和一般智力方面的表现更好。结果还表明，与非吸烟的 ALC 相比，吸烟的 ALC 在多个神经认知领域的表现较差，这与 COMT 或 BDNF 基因型无关。总的来说，这些发现支持了将戒烟计划提供给酒精/物质使用障碍治疗开始时的吸烟者的临床扩展运动。
