Department of Psicologia Basica, Faculty of Psychology, University of Barcelona, 08035 Barcelona, Spain.
Cereb Cortex. 2010 Aug;20(8):1985-96. doi: 10.1093/cercor/bhp263. Epub 2009 Dec 27.
People's sensitivity to reinforcing stimuli such as monetary gains and losses shows a wide interindividual variation that might in part be determined by genetic differences. Because of the established role of the dopaminergic system in the neural encoding of rewards and negative events, we investigated young healthy volunteers being homozygous for either the Valine or Methionine variant of the catechol-O-methyltransferase (COMT) codon 158 polymorphism as well as homozygous for the C or T variant of the SNP -521 polymorphism of the dopamine D4 receptor. Participants took part in a gambling paradigm featuring unexpectedly high monetary gains and losses in addition to standard gains/losses of expected magnitude while undergoing functional magnetic resonance imaging at 3 T. Valence-related brain activations were seen in the ventral striatum, the anterior cingulate cortex, and the inferior parietal cortex. These activations were modulated by the COMT polymorphism with greater effects for valine/valine participants but not by the D4 receptor polymorphism. By contrast, magnitude-related effects in the anterior insula and the cingulate cortex were modulated by the D4 receptor polymorphism with larger responses for the CC variant. These findings emphasize the differential contribution of genetic variants in the dopaminergic system to various aspects of reward processing.
人们对金钱收益和损失等强化刺激的敏感性存在广泛的个体差异，这种差异部分可能取决于遗传差异。由于多巴胺能系统在神经编码奖励和负性事件中的既定作用，我们调查了携带儿茶酚-O-甲基转移酶（COMT）密码子 158 多态性 Valine 或 Methionine 变体的纯合子以及多巴胺 D4 受体 SNP -521 多态性 C 或 T 变体的纯合子的年轻健康志愿者。参与者在 3T 功能磁共振成像下参与了一个赌博范式，除了标准的预期收益/损失外，还会出现意外的高金钱收益和损失。在腹侧纹状体、前扣带皮层和下顶叶皮层中观察到与效价相关的大脑激活。这些激活受到 COMT 多态性的调节，Valine/Valine 参与者的影响更大，但不受 D4 受体多态性的影响。相比之下，在前脑岛和扣带皮层中与幅度相关的效应受 D4 受体多态性的调节，CC 变体的反应更大。这些发现强调了多巴胺能系统中的遗传变异对奖励处理各个方面的不同贡献。
