OBJECTIVE The present investigation tested the association of a novel measure of brain activation recorded during a simple motor inhibition task with a GRM8 genetic locus implicated in risk for substance dependence. METHODS 122 European-American adults were genotyped at rs1361995 and evaluated against DSM-IV criteria for Alcohol Dependence, Cocaine Dependence, Conduct Disorder, and Antisocial Personality Disorder. Also, their brain activity was recorded in response to rare, so-called "No-Go" stimuli presented during a continuous performance test. Brain activity was quantified with two indices: (1) the amplitude of the No-Go P300 electroencephalographic response averaged across trials; and (2) the inter-trial variability of the response. RESULTS The absence of the minor allele at the candidate locus was associated with all of the evaluated diagnoses. In comparison to minor allele carriers, major allele homozygotes also demonstrated increased inter-trial variability in No-Go P300 response amplitude but no difference in average amplitude. CONCLUSIONS GRM8 genotype is associated with Alcohol and Cocaine Dependence as well as personality risk factors for dependence. The association may be mediated through an inherited instability in brain function that affects cognitive control. SIGNIFICANCE The present study focuses on a metric and brain mechanism not typically considered or theorized in studies of patients with substance use disorders.

中文翻译：

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GRM8 基因型与反应抑制任务期间大脑激活的外化障碍和更大的试验间变异相关

目标本研究测试了在简单运动抑制任务期间记录的一种新的大脑激活测量与涉及物质依赖风险的 GRM8 基因座之间的关联。方法 122 名欧洲-美国成年人在 rs1361995 进行基因分型，并根据 DSM-IV 酒精依赖、可卡因依赖、行为障碍和反社会人格障碍的标准进行评估。此外，他们的大脑活动被记录下来，以响应在连续性能测试中出现的罕见的、所谓的“No-Go”刺激。大脑活动用两个指标量化：（1）No-Go P300 脑电图反应的幅度在试验中平均；(2) 反应的试验间变异性。结果 候选基因座不存在次要等位基因与所有评估的诊断相关。与次要等位基因携带者相比，主要等位基因纯合子也表现出 No-Go P300 响应幅度的试验间变异性增加，但平均幅度没有差异。结论 GRM8 基因型与酒精和可卡因依赖以及依赖的人格风险因素有关。这种关联可能是通过影响认知控制的大脑功能的遗传不稳定性来介导的。意义 本研究侧重于物质使用障碍患者研究中通常未考虑或理论化的度量和大脑机制。主要等位基因纯合子也表现出 No-Go P300 响应幅度的试验间变异性增加，但平均幅度没有差异。结论 GRM8 基因型与酒精和可卡因依赖以及依赖的人格风险因素有关。这种关联可能是通过影响认知控制的大脑功能的遗传不稳定性来介导的。意义 本研究侧重于物质使用障碍患者研究中通常未考虑或理论化的度量和大脑机制。主要等位基因纯合子也表现出 No-Go P300 响应幅度的试验间变异性增加，但平均幅度没有差异。结论 GRM8 基因型与酒精和可卡因依赖以及依赖的人格危险因素有关。这种关联可能是通过影响认知控制的大脑功能的遗传不稳定性来介导的。意义 本研究侧重于物质使用障碍患者研究中通常未考虑或理论化的度量和大脑机制。