Multilocus genetic composite reflecting dopamine signaling capacity predicts reward circuitry responsivity.
Multilocus genetic composite reflecting dopamine signaling capacity predicts reward circuitry responsivity.
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DOI：
10.1523/jneurosci.1506-12.2012
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发表时间：
2012-07-18
期刊：
影响因子：
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通讯作者：
Smolen A
中科院分区：
文献类型：
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作者：
Stice E;Yokum S;Burger K;Epstein L;Smolen A
检验以下假设：具有与低多巴胺（DA）信号传导能力相关的puristic基因型的人，包括TaqIA A1等位基因、DRD 2 - 141 C Ins/Ins基因型、DRD 4 7-重复或更长的等位基因、DAT 1 10-重复等位基因和Met/Met COMT基因型，以及每个多位点复合物中具有更多这些基因型的人，显示出主要依赖DA信号传导的奖励区域的响应性较低。功能磁共振成像（fMRI）的范例被用来调查激活响应接收和预期接收可口的食物和金钱奖励。使用标准方法从唾液中提取DNA。160名青少年（平均年龄= 15.3，SD = 1.07;平均BMI = 20.8，SD = 1.9）。功能磁共振成像范例中的血氧水平依赖性激活。数据证实，这些功能磁共振成像范式激活奖励，注意，体感和味觉区域。与没有这五种基因型的个体相比，基于DA的奖励区域的激活并没有表现出更少，但是那些具有Met/Met与瓦尔/瓦尔COMT基因型的个体显示出更少的颞中回激活，而那些具有DRD 4-L与DRD 4-S基因型的个体显示出更少的枕中回激活。重要的是，多位点综合评分显示，这些基因型数量较多的人在奖励区域（包括壳核、尾状核和海马）对金钱奖励的反应较少。结果表明，多位点的遗传复合物是一个更敏感的指标脆弱性低奖励区域的反应比个人基因型。
Test the hypotheses that humans with genotypes putatively associated with low dopamine (DA) signaling capacity, including the TaqIA A1 allele, DRD2-141C Ins/Ins genotype, DRD4 7-repeat or longer allele, DAT1 10-repeat allele, and the Met/Met COMT genotype, and with a greater number of these genotypes per a multilocus composite, show less responsivity of reward regions that primarily rely on DA-signaling. Functional magnetic resonance imaging (fMRI) paradigms were used to investigate activation in response to receipt and anticipated receipt of palatable food and monetary reward. DNA was extracted from saliva using standard methods. One-hundred and sixty adolescents (Mean age = 15.3, SD = 1.07; Mean BMI = 20.8, SD = 1.9). Blood oxygen level dependent activation in the fMRI paradigms. Data confirmed that these fMRI paradigms activated reward, attention, somatosensory, and gustatory regions. Individuals with versus without these five genotypes did not show less activation of DA-based reward regions, but those with the Met/Met versus the Val/Val COMT genotype showed less middle temporal gyrus activation and those with the DRD4-L versus the DRD4-S genotype showed less middle occipital gyrus activation in response to monetary reward. Critically, the multilocus composite score revealed that those with a greater number of these genotypes showed less activation in reward regions, including the putamen, caudate, and insula, in response to monetary reward. Results suggest that the multilocus genetic composite is a more sensitive index of vulnerability for low reward region responsivity than individual genotypes.