GABRB1 Single Nucleotide Polymorphism Associated with Altered Brain Responses (but not Performance) during Measures of Impulsivity and Reward Sensitivity in Human Adolescents.
GABRB1 Single Nucleotide Polymorphism Associated with Altered Brain Responses (but not Performance) during Measures of Impulsivity and Reward Sensitivity in Human Adolescents.
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DOI：
10.3389/fnbeh.2017.00024
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发表时间：
2017
影响因子：
3
通讯作者：
Stephens DN
中科院分区：
文献类型：
--
作者：
Duka T;Nikolaou K;King SL;Banaschewski T;Bokde AL;Büchel C;Carvalho FM;Conrod PJ;Flor H;Gallinat J;Garavan H;Heinz A;Jia T;Gowland P;Martinot JL;Paus T;Rietschel M;Robbins TW;Smolka M;Schumann G;Stephens DN
编码多种 GABAA 受体的基因变异与人类吸毒和酗酒有关。其中，许多人类研究表明，GABRB1（编码 GABAA 受体 β1 亚基的基因）与酒精依赖 (AD) 之间存在关联，无论是其本身还是与其他物质依赖和精神疾病共存。在本研究中，我们假设，GABRB1 基因相关的酗酒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（Schumann 等人），我们在人类青少年群体中探讨了单核苷酸多态性 (SNP) rs2044081 的次要 (T) 变体的拥有是否与测量与药物和酒精滥用有关的冲动性和奖赏敏感性任务的执行情况相关。等位基因变异与测量冲动某一方面的停止信号任务（SST）或评估奖励预期的货币激励延迟（MID）任务中的表现改变无关。然而，在 MID 表现期间，右半球额下回 (IFG)、左半球尾状/岛叶和左半球颞下回 (ITG) 功能性磁共振成像 (fMRI) 血氧水平依赖性 (BOLD) 反应的增加在小 (T) 等位基因组中较高。相反，在 SST 表现期间，在右半球边缘上回、右半球舌和左半球顶下回发现的 BOLD 反应表明次要基因型的反应减少。我们认为，含有 β1 的 GABAA 受体可能在控制奖励相关行为的重要大脑区域的兴奋性中发挥作用，这可能导致对成瘾行为的易感性。
Variations in genes encoding several GABAA receptors have been associated with human drug and alcohol abuse. Among these, a number of human studies have suggested an association between GABRB1, the gene encoding GABAA 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 GABRB1 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.,), 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 GABAA receptors may play a role in excitability of brain regions important in controlling reward-related behavior, which may contribute to susceptibility to addictive behavior.