Identifying Neurobiological Phenotypes Associated with Alcohol Use Disorder Severity
Identifying Neurobiological Phenotypes Associated with Alcohol Use Disorder Severity
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DOI：
10.1038/npp.2011.99
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发表时间：
2011-09-01
影响因子：
7.6
通讯作者：
Hutchison, Kent E.
中科院分区：
文献类型：
--
作者：
Claus, Eric D.;Ewing, Sarah W. Feldstein;Hutchison, Kent E.
尽管大量研究普遍支持遗传因素在酒精使用障碍（AUDs）风险中的重要性，但候选基因和全基因组研究尚未确定一组遗传变异，这些变异解释了AUDs差异的重要部分。原因之一是遗传研究中使用的酒精相关表型通常基于高度异质的诊断类别。因此，确定与驱动AUDs发展的神经适应相关的神经生物学表型对于遗传和表观遗传研究的未来成功至关重要。一种这样的神经生物学表型是暴露在酒精味道线索下基底神经节、前额叶皮层和运动区域的调动程度，所有这些在动物研究中都被证明在成瘾行为中起着关键作用。为此，本研究旨在通过体素和功能连通性测量，在大样本（n = 326）中检查这些结构的线索引发反应是否与AUD严重程度相关。结果表明，酒精刺激显著激活背纹状体、脑岛/眶额叶皮层、前扣带皮层和腹侧被盖区。AUD的严重程度与涉及激励显著性的区域如伏隔核和杏仁核有中等相关性，与楔前叶、岛状体和背纹状体的相关性更强。研究结果表明，AUDs与这些区域的神经适应性有关，这些指标可能代表了后续遗传研究的重要神经生物学表型。神经精神药理学（2011）36,2086-2096；doi: 10.1038 / npp.2011.99;2011年6月15日在线发布
Although numerous studies provide general support for the importance of genetic factors in the risk for alcohol use disorders (AUDs), candidate gene and genome-wide studies have yet to identify a set of genetic variations that explain a significant portion of the variance in AUDs. One reason is that alcohol-related phenotypes used in genetic studies are typically based on highly heterogeneous diagnostic categories. Therefore, identifying neurobiological phenotypes related to neuroadaptations that drive the development of AUDs is critical for the future success of genetic and epigenetic studies. One such neurobiological phenotype is the degree to which exposure to alcohol taste cues recruits the basal ganglia, prefrontal cortex, and motor areas, all of which have been shown to have a critical role in addictive behaviors in animal studies. To that end, this study was designed to examine whether cue-elicited responses of these structures are associated with AUD severity in a large sample (n = 326) using voxelwise and functional connectivity measures. Results suggested that alcohol cues significantly activated dorsal striatum, insula/orbitofrontal cortex, anterior cingulate cortex, and ventral tegmental area. AUD severity was moderately correlated with regions involved in incentive salience such as the nucleus accumbens and amygdala, and stronger relationships with precuneus, insula, and dorsal striatum. The findings indicate that AUDs are related to neuroadaptations in these regions and that these measures may represent important neurobiological phenotypes for subsequent genetic studies. Neuropsychopharmacology (2011) 36, 2086-2096; doi: 10.1038/npp.2011.99; published online 15 June 2011