Association of COMT and SLC6A3 polymorphisms with impulsivity, response inhibition and brain function
Association of COMT and SLC6A3 polymorphisms with impulsivity, response inhibition and brain function
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COMT 和 SLC6A3 多态性与冲动、反应抑制和脑功能的关联
DOI：
10.1016/j.cortex.2015.07.002
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发表时间：
2015
期刊：
影响因子：
3.6
通讯作者：
Ettinger U
中科院分区：
文献类型：
--
作者：
Kasparbauer AM;Merten N;Aichert DS;Wöstmann N;Meindl T;Rujescu D;Ettinger U
抑制控制的遗传相关性的证据很少。两个先前研究的多巴胺相关的多态性，COMT rs 4680和SLC 6A 33 ′ UTR 40-base-pair VNTR（rs 28363170），已经与反应抑制相关，但结果不一致。在这里，我们调查了这两个多态性在一个大的健康成人样本（N= 515）的反应抑制电池，包括antisaccade，停止信号，去/不去和Stroop任务，以及冲动的心理测量（Barratt冲动量表）（实验1）的影响。此外，一个子样本（N= 144）进行了研究，而在3 T功能磁共振成像（实验2）中执行的去/不去，停止信号和antisaccade任务。在实验1中，我们没有发现任何显着协会的COMTorSLC 6A 3与抑制性能或冲动。在实验2中，未发现COMT与BOLD相关，但在所有抑制性对照中，SLC 6A 3基因型的主效应是一致的：10 R等位基因的纯合性比至少有一个9 R等位基因的基因型与更大的额-纹状体BOLD反应相关。这些发现与荟萃分析一致，荟萃分析显示10 R等位基因与纹状体多巴胺转运蛋白表达减少相关，在动物研究中发现其导致细胞外多巴胺水平增加。因此，我们的研究支持纹状体多巴胺参与认知控制的神经机制，特别是反应抑制。
Evidence of the genetic correlates of inhibitory control is scant. Two previously studied dopamine-related polymorphisms, COMT rs4680 and theSLC6A33′ UTR 40-base-pair VNTR (rs28363170), have been associated with response inhibition, however with inconsistent findings. Here, we investigated the influence of these two polymorphisms in a large healthy adult sample (N= 515) on a response inhibition battery including the antisaccade, stop-signal, go/no-go and Stroop tasks as well as a psychometric measure of impulsivity (Barratt Impulsiveness Scale) (Experiment 1). Additionally, a subsample (N= 144) was studied while performing the go/no-go, stop-signal and antisaccade tasks in 3T fMRI (Experiment 2). In Experiment 1, we did not find any significant associations ofCOMTorSLC6A3with inhibitory performance or impulsivity. In Experiment 2, no association ofCOMTwith BOLD was found. However, there were consistent main effects ofSLC6A3genotype in all inhibitory contrasts: Homozygosity of the 10R allele was associated with greater fronto–striatal BOLD response than genotypes with at least one 9R allele. These findings are consistent with meta-analyses showing that the 10R allele is associated with reduced striatal dopamine transporter expression, which in animal studies has been found to lead to increased extracellular dopamine levels. Our study thus supports the involvement of striatal dopamine in the neural mechanisms of cognitive control, in particular response inhibition.
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影响因子：
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作者：
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影响因子：
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通讯作者：
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