Caldú Xavier, Vendrell Pere, Bartrés-Faz David, Clemente Inmaculada, Bargalló Núria, Jurado María Angeles, Serra-Grabulosa Josep Maria, Junqué Carme
Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, and Department of Radiology, Centre de Diagnòstic per la Image, Hospital Clínic de Barcelona, Spain.
Neuroimage. 2007 Oct 1;37(4):1437-44. doi: 10.1016/j.neuroimage.2007.06.021. Epub 2007 Jul 4.
Two limiting factors of dopamine activity are the catechol-o-methyltransferase (COMT) and the dopamine transporter (DAT), which terminate dopamine activity by degradation and uptake, respectively. Genetic variants of COMT and DAT have been related to the enzymatic activity and protein availability, respectively. The Met allele of the COMT Val108/158 Met polymorphism has been associated to lower enzymatic activity and the 9-repeat allele of the DAT 40 base-pair (bp) variable number of tandem repeat (VNTR) polymorphism has been related to lower protein availability. Genotypes for COMT and DAT were determined in a sample of 75 healthy subjects, who underwent functional magnetic resonance imaging (fMRI) while performing an N-back task. To further assess the effects of the genotypes on cognition, subjects were administered the Wisconsin Card Sorting Test (WCST) and the Continuous Performance Test (CPT). Analysis of fMRI data revealed an additive effect of these two genes on brain activation in an N-back task, with subjects homozygous for the Val and the 9-repeat alleles showing the highest activation for the same level of performance. Moreover, the Val allele was related to higher number of perseverative errors on the WCST and with a higher number of commission errors on the CPT. The 10-repeat allele was associated with faster reaction times but also with a higher number of commission errors. Our results support a role of the COMT Val108/158 Met and the DAT 40 bp VNTR in both brain activation and cognition.
多巴胺活性的两个限制因素是儿茶酚-O-甲基转移酶（COMT）和多巴胺转运体（DAT），它们分别通过降解和摄取来终止多巴胺活性。COMT和DAT的基因变异分别与酶活性和蛋白质可用性有关。COMT Val108/158 Met多态性的Met等位基因与较低的酶活性相关，而DAT 40碱基对（bp）可变数目串联重复序列（VNTR）多态性的9重复等位基因与较低的蛋白质可用性有关。在75名健康受试者的样本中确定了COMT和DAT的基因型，这些受试者在执行N-back任务时接受了功能磁共振成像（fMRI）。为了进一步评估基因型对认知的影响，对受试者进行了威斯康星卡片分类测试（WCST）和连续性能测试（CPT）。fMRI数据分析显示，在N-back任务中，这两个基因对大脑激活有累加效应，对于相同的表现水平，Val和9重复等位基因纯合的受试者表现出最高的激活。此外，Val等位基因与WCST上更多的持续性错误以及CPT上更多的错误相关。10重复等位基因与更快的反应时间相关，但也与更多的错误相关。我们的结果支持COMT Val108/158 Met和DAT 40 bp VNTR在大脑激活和认知中的作用。
