Genetic Variability in the Dopamine System (Dopamine Receptor D4, Catechol-O-Methyltransferase) Modulates Neurophysiological Responses to Gains and Losses
Genetic Variability in the Dopamine System (Dopamine Receptor D4, Catechol-O-Methyltransferase) Modulates Neurophysiological Responses to Gains and Losses
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DOI：
10.1016/j.biopsych.2009.01.006
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发表时间：
2009-07-15
影响因子：
10.6
通讯作者：
Rodriguez-Fornells, Antoni
中科院分区：
文献类型：
--
作者：
Marco-Pallares, Josep;Cucurell, David;Rodriguez-Fornells, Antoni
背景：奖励过程中的个体间差异可能部分由多巴胺系统的遗传差异来解释。在这里，我们研究大脑的反应是否正常人受试者的事件相关电位[ERPs]（振荡活动）对金钱收益和损失的调节是两种多巴胺能多态性的函数（儿茶酚-O-甲基转移酶[COMT]缬氨酸[VaI] 158甲硫氨酸[Met]，多巴胺受体D4 [DRD 4]单核苷酸多态性[SNP] -521）。从更大的人群中选择40名两种多态性的不同等位基因纯合子的参与者，以评估主要效应和相互作用。基于阶段性/紧张性多巴胺的假设，我们预计增加的大脑反应的损失和收益的参与者纯合子的瓦尔/瓦尔变异的COMT多态性（相关的更高的酶活性）。结果：内侧额叶负波（MFN）的ERP和增加β功率增益增强的参与者纯合子的COMT Val瓦尔等位基因相比，纯合子MetMet参与者。相比之下，没有调制增益和损失相关的大脑活动被发现是DRD 4 SNP-521 polymorphism.Conclusions的功能：结果表明COMT瓦尔/Met多态性在奖励的处理中的作用，与理论解释一致，表明多巴胺在MFN和β功率增加生成中的可能作用。此外，目前的结果可能同意阶段性/紧张性多巴胺理论，预测更高的阶段性多巴胺反应ValVal参与者。
Background: Interindividual variability in the processing of reward might be partially explained by genetic differences in the dopamine system. Here, we study whether brain responses (event-related potentials [ERPs], oscillatory activity) to monetary gains and losses in normal human subjects are modulated as a function of two dopaminergic polymorphisms (catechol-O-methyltransferase [COMT] valine [VaI]158methionine [Met], dopamine receptor D4 [DRD4] single nucleotide polymorphism [SNP] -521).Methods: Forty participants homozygous for the different alleles of both polymorphisms were selected from a larger population to assess the main effects and interactions. Based on the phasic/tonic dopamine hypothesis, we expected increased brain responses to losses and gains in participants homozygous for the Val/Val variant of the COMT polymorphism (related to higher enzyme activity).Results: The medial frontal negativity (MFN) of the ERP and the increase in beta power for gains were enhanced for participants homozygous for the COMT ValVal allele when compared with homozygous MetMet participants. In contrast, no modulations in gain- and loss-related brain activity were found to be a function of the DRD4 SNP -521 polymorphism.Conclusions: The results demonstrate the role of the COMT Val/Met polymorphism in the processing of reward, consistent with theoretical explanations that suggest the possible role of dopamine in the MFN and beta power increase generation. In addition, the present results might agree with the phasic/tonic dopamine theory that predicts higher phasic dopamine responses in ValVal participants.