Center for BrainHealth, School of Behavioral and Brain Sciences, University of Texas, Dallas, Dallas, TX, USA.
Addict Biol. 2012 Nov;17(6):1046-56. doi: 10.1111/j.1369-1600.2011.00328.x. Epub 2011 May 6.
Compulsion in alcohol use disorders (AUD) has been attributed to impairment in response inhibition. Because genes that regulate dopamine (DA) have been implicated not only for risk for AUD but also for impulsivity based on behavioral studies, we set out to examine the underlying neural mechanisms associated with these effects. We collected functional magnetic resonance imaging images on 53 heavy drinking but otherwise healthy adults while performing the Go/NoGo task. We predicted that genetic variants previously reported in the literature to be associated with substance abuse, specifically the DRD2 rs1799732 and DRD4 VNTR, will modulate neural processes underlying response inhibition. Our results showed differential neural response for the DRD4 VNTR during successful inhibition in the inferior frontal gyrus (IFG) (cluster-corrected P<0.05, z=1.9). Similarly, DRD2 rs1799732 groups were significantly different in the precuneus and cingulate gyrus during successful response inhibition (cluster-corrected P<0.05, z=1.9). These findings provide further evidence for the role of DAergic genes in modulating neural response in areas that underlie response inhibition and self-monitoring processes. Variants within these genes appear to influence processes related to impulsive behavior, which may increase one's risk for alcohol abuse and dependence.
酒精使用障碍（AUD）中的强迫行为归因于反应抑制受损。由于调节多巴胺（DA）的基因不仅与 AUD 的风险有关，而且与基于行为研究的冲动性有关，因此我们着手研究与这些效应相关的潜在神经机制。我们在 53 名大量饮酒但其他方面健康的成年人中收集了功能磁共振成像图像，同时执行 Go/NoGo 任务。我们预测，先前文献中报道与物质滥用相关的遗传变异，特别是 DRD2 rs1799732 和 DRD4 VNTR，将调节反应抑制的潜在神经过程。我们的研究结果表明，在成功抑制时，DRD4 VNTR 在额下回（IFG）中表现出不同的神经反应（聚类校正后 P<0.05，z=1.9）。同样，在成功抑制时，DRD2 rs1799732 组在楔前叶和扣带回的差异显著（聚类校正后 P<0.05，z=1.9）。这些发现为 DA 能基因在调节反应抑制和自我监测过程中潜在神经反应的作用提供了进一步的证据。这些基因内的变异似乎影响与冲动行为相关的过程，这可能会增加一个人对酒精滥用和依赖的风险。
