Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL 60637, USA.
Exp Clin Psychopharmacol. 2009 Dec;17(6):374-83. doi: 10.1037/a0017840.
The dopamine D2 receptor (DRD2) appears to be involved in impulsive behaviors, and particularly in behavioral inhibition. We sought to determine whether inhibition and impulsivity were related to genetic polymorphisms in the DRD2 gene (DRD2) in healthy volunteers (N = 93). Participants received placebo or d-amphetamine in random order. They performed the stop task, measuring behavioral inhibition, and rated their mood states on each session. They also completed the Zuckerman-Kuhlman Personality Questionnaire, including an Impulsivity subscale. We investigated the association between 12 single nucleotide polymorphisms (SNPs) and haplotypes in DRD2 and stop task performance in the nondrug (i.e., placebo) session and on the personality measure of impulsivity. We secondarily evaluated the DRD2 SNPs in relation to response to d-amphetamine on stop task performance and mood ratings. Mood was not related to genotypes in either the drug free condition or in response to drug. However, 2 SNPs, rs4648317 and rs12364283, and a haplotype block consisting of those SNPs, were associated with better performance on the stop task in the drug free condition and lower scores on the Impulsivity subscale. We also found that rs12364283 was associated with effects of d-amphetamine on stop task performance: d-amphetamine decreased stop reaction time (RT) in the A/A group but increased stop RT in the combined A/G + G/G genotype. Of the SNPs we evaluated, rs12364283, which has been associated with DRD2 expression, was the most significantly associated with inhibition and impulsivity. The significant relationship between DRD2 genotype and both behavioral inhibition and impulsivity suggests a possible common genetic influence on behavioral and self-report measures of impulsivity.
多巴胺 D2 受体（DRD2）似乎与冲动行为有关，尤其是与行为抑制有关。我们试图确定健康志愿者（N=93）中 DRD2 基因（DRD2）的遗传多态性是否与抑制和冲动有关。参与者随机接受安慰剂或 d-安非他命。他们进行了停止任务，测量行为抑制，并在每次会议上对自己的情绪状态进行评分。他们还完成了 Zuckerman-Kuhlman 人格问卷，其中包括冲动性子量表。我们研究了 DRD2 中的 12 个单核苷酸多态性（SNP）和单倍型与非药物（即安慰剂）条件下停止任务表现以及冲动性人格测量之间的关系。我们还评估了 DRD2 SNP 与停止任务表现和情绪评分对 d-安非他命的反应之间的关系。在无药物条件下或对药物的反应中，情绪与基因型均无关系。然而，2 个 SNP（rs4648317 和 rs12364283）以及由这些 SNP 组成的单倍型块与无药物条件下停止任务表现更好以及冲动性子量表得分较低有关。我们还发现，rs12364283 与 d-安非他命对停止任务表现的影响有关：在 A/A 组中，d-安非他命降低了停止反应时间（RT），但在 A/G+G/G 基因型中增加了停止 RT。在我们评估的 SNP 中，与 DRD2 表达相关的 rs12364283 与抑制和冲动性的相关性最显著。DRD2 基因型与行为抑制和冲动性的显著关系表明，行为和自我报告的冲动性测量可能存在共同的遗传影响。
