The Effects of COMT (Val108/158Met) and DRD4 (SNP-521) Dopamine Genotypes on Brain Activations Related to Valence and Magnitude of Rewards
The Effects of COMT (Val108/158Met) and DRD4 (SNP-521) Dopamine Genotypes on Brain Activations Related to Valence and Magnitude of Rewards
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DOI：
10.1093/cercor/bhp263
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发表时间：
2010-08-01
期刊：
影响因子：
3.7
通讯作者：
Muente, Thomas F.
中科院分区：
文献类型：
--
作者：
Camara, Estela;Kraemer, Ulrike M.;Muente, Thomas F.
人们对强化刺激的敏感性，如金钱的收益和损失，表现出很大的个体差异，这可能部分是由遗传差异决定的。由于多巴胺能系统在奖赏和负性事件的神经编码中的既定作用，我们调查了年轻健康志愿者，他们是儿茶酚-O-甲基转移酶（COMT）密码子158多态性的缬氨酸或蛋氨酸变体的纯合子，以及多巴胺04受体SNP 521多态性的C或T变体的纯合子。参与者参加了一个赌博范例，其特点是在进行3 T功能性磁共振成像时，除了预期幅度的标准收益/损失之外，还出现了意外的高货币收益和损失。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脑激活。这些激活受COMT多态性调节，对缬氨酸/缬氨酸参与者的影响更大，但不受04受体多态性的影响。相比之下，在前额叶和扣带皮层的幅度相关的影响调制的D4受体多态性与CC变异较大的反应。这些发现强调了多巴胺能系统中遗传变异对奖赏处理各个方面的不同贡献。
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 04 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 04 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.