Duka Theodora, Nikolaou Kyriaki, King Sarah L, Banaschewski Tobias, Bokde Arun L W, Büchel Christian, Carvalho Fabiana M, Conrod Patricia J, Flor Herta, Gallinat Jürgen, Garavan Hugh, Heinz Andreas, Jia Tianye, Gowland Penny, Martinot Jean-Luc, Paus Tomáš, Rietschel Marcella, Robbins Trevor W, Smolka Michael, Schumann Gunter, Stephens David N
School of Psychology, University of Sussex Falmer, UK.
Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University Mannheim, Germany.
Front Behav Neurosci. 2017 Feb 15;11:24. doi: 10.3389/fnbeh.2017.00024. eCollection 2017.
Variations in genes encoding several GABA receptors have been associated with human drug and alcohol abuse. Among these, a number of human studies have suggested an association between , the gene encoding GABA receptor β1 subunits, with Alcohol dependence (AD), both on its own and comorbid with other substance dependence and psychiatric illnesses. In the present study, we hypothesized that the genetically-associated increased risk for developing alcoholism may be associated with impaired behavioral control and altered sensitivity to reward, as a consequence of altered brain function. Exploiting the IMAGEN database (Schumann et al., 2010), we explored in a human adolescent population whether possession of the minor (T) variant of the single nucleotide polymorphism (SNP) rs2044081 is associated with performance of tasks measuring aspects of impulsivity, and reward sensitivity that are implicated in drug and alcohol abuse. Allelic variation did not associate with altered performance in either a stop-signal task (SST), measuring one aspect of impulsivity, or a monetary incentive delay (MID) task assessing reward anticipation. However, increased functional magnetic resonance imaging (fMRI) blood-oxygen-level dependent (BOLD) response in the right hemisphere inferior frontal gyrus (IFG), left hemisphere caudate/insula and left hemisphere inferior temporal gyrus (ITG) during MID performance was higher in the minor (T) allelic group. In contrast, during SST performance, the BOLD response found in the right hemisphere supramarginal gyrus, right hemisphere lingual and left hemisphere inferior parietal gyrus indicated reduced responses in the minor genotype. We suggest that β1-containing GABA receptors may play a role in excitability of brain regions important in controlling reward-related behavior, which may contribute to susceptibility to addictive behavior.
编码几种γ-氨基丁酸（GABA）受体的基因变异与人类药物和酒精滥用有关。其中，多项人体研究表明，编码GABA受体β1亚基的基因 与酒精依赖（AD）之间存在关联，该基因本身以及与其他物质依赖和精神疾病共病时均如此。在本研究中，我们假设，基因相关的酒精中毒风险增加可能与行为控制受损和对奖励的敏感性改变有关，这是大脑功能改变的结果。利用IMAGEN数据库（舒曼等人，2010年），我们在人类青少年群体中探究了单核苷酸多态性（SNP）rs2044081的次要（T）变体的拥有情况是否与测量冲动性方面以及与药物和酒精滥用有关的奖励敏感性的任务表现相关。等位基因变异与在测量冲动性一个方面的停止信号任务（SST）或评估奖励预期的金钱激励延迟（MID）任务中的表现改变均无关联。然而，在MID任务执行期间，次要（T）等位基因组右侧半球额下回（IFG）、左侧半球尾状核/脑岛和左侧半球颞下回（ITG）的功能磁共振成像（fMRI）血氧水平依赖（BOLD）反应增强。相比之下，在SST任务执行期间，在右侧半球缘上回、右侧半球舌回和左侧半球顶下小叶发现的BOLD反应表明次要基因型的反应减弱。我们认为，含β1的GABA受体可能在控制与奖励相关行为的重要脑区兴奋性中发挥作用，这可能导致成瘾行为易感性增加。
