Nees F, Witt S H, Dinu-Biringer R, Lourdusamy A, Tzschoppe J, Vollstädt-Klein S, Millenet S, Bach C, Poustka L, Banaschewski T, Barker G J, Bokde A L W, Bromberg U, Büchel C, Conrod P J, Frank J, Frouin V, Gallinat J, Garavan H, Gowland P, Heinz A, Ittermann B, Mann K, Martinot J-L, Paus T, Pausova Z, Robbins T W, Smolka M N, Rietschel M, Schumann G, Flor H
Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Division of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Alcohol. 2015 Mar;49(2):103-10. doi: 10.1016/j.alcohol.2014.12.004. Epub 2015 Jan 7.
Changes in reward processing have been identified as one important pathogenetic mechanism in alcohol addiction. The nonsynonymous single nucleotide polymorphism in the brain-derived neurotrophic factor (BDNF) gene (rs6265/Val66Met) modulates the central nervous system activity of neurotransmitters involved in reward processing such as serotonin, dopamine, and glutamate. It was identified as crucial for alcohol consumption in healthy adults and, in rats, specifically related to the function in the striatum, a region that is commonly involved in reward processing. However, studies in humans on the association of BDNF Val66Met and reward-related brain functions and its role for alcohol consumption, a significant predictor of later alcohol addiction, are missing. Based on an intermediate phenotype approach, we assessed the early orientation toward alcohol and alcohol consumption in 530 healthy adolescents that underwent a monetary incentive delay task during functional magnetic resonance imaging. We found a significantly lower response in the putamen to reward anticipation in adolescent Met carriers with high versus low levels of alcohol consumption. During reward feedback, Met carriers with low putamen reactivity were significantly more likely to orient toward alcohol and to drink alcohol 2 years later. This study indicates a possible effect of BDNF Val66Met on alcohol addiction-related phenotypes in adolescence.
奖赏处理的改变已被确定为酒精成瘾的一种重要发病机制。脑源性神经营养因子（BDNF）基因中的非同义单核苷酸多态性（rs6265/Val66Met）调节参与奖赏处理的神经递质（如血清素、多巴胺和谷氨酸）的中枢神经系统活性。它被确定对健康成年人的饮酒行为至关重要，在大鼠中，它与纹状体的功能特别相关，而纹状体是一个通常参与奖赏处理的区域。然而，关于BDNF Val66Met与奖赏相关脑功能的关联及其在饮酒行为（后期酒精成瘾的一个重要预测因素）中的作用的人体研究尚属空白。基于中间表型方法，我们对530名健康青少年进行了评估，这些青少年在功能磁共振成像期间接受了金钱激励延迟任务，以研究他们对酒精的早期倾向和饮酒行为。我们发现，在高酒精摄入量与低酒精摄入量的青少年Met携带者中，壳核对奖赏预期的反应显著降低。在奖赏反馈期间，壳核反应性低的Met携带者在两年后更有可能倾向于酒精并饮酒。这项研究表明BDNF Val66Met可能对青少年酒精成瘾相关表型有影响。
