GENETIC MARKERS OF STRIATAL DOPAMINE PREDICT INDIVIDUAL DIFFERENCES IN DYSFUNCTIONAL, BUT NOT FUNCTIONAL IMPULSIVITY
GENETIC MARKERS OF STRIATAL DOPAMINE PREDICT INDIVIDUAL DIFFERENCES IN DYSFUNCTIONAL, BUT NOT FUNCTIONAL IMPULSIVITY
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DOI：
10.1016/j.neuroscience.2010.07.050
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发表时间：
2010-10-27
期刊：
影响因子：
3.3
通讯作者：
Hommel, B.
中科院分区：
文献类型：
--
作者：
Colzato, L. S.;van den Wildenberg, W. P. M.;Hommel, B.
各种精神疾病的特征是冲动水平升高。虽然大量的证据支持纹状体，但不是额叶多巴胺（DA）在人类冲动性中的特定作用，最近的遗传变异性研究提出了一些怀疑这样的作用。重要的是，冲动性由两个不可分离的组成部分组成，以前的研究未能将其分开：功能性冲动和功能失调性冲动。我们比较了具有相对较高纹状体DA水平的遗传易感性的参与者（DAT 1 9-重复携带者，DRD 2 C957 T/T纯合子和DRD 4 7-重复携带者）与具有其他遗传易感性的参与者。我们预测，第一组会表现出高分数的功能障碍，但不是功能，自我报告的冲动和更大的困难，抑制行为反应停止信号，冲动的行为措施。在130名健康成人中，我们研究了DAT 1、DRD 4和DRD 2基因C957 T多态性之间的关系（与纹状体DA相关的多态性）和儿茶酚-O-甲基转移酶（COMT）Val 158 Met（与额叶DA相关的多态性）对自我报告的功能障碍和功能性冲动的影响，通过Dickman冲动量表（DII）评估，以及抑制控制的效率，通过停止信号范例进行评估。DRD 2 C957 T/T纯合子和DRD 4 7-重复携带者在自我报告的功能障碍性冲动上确实有显著更高的分数，但不是功能性冲动。TIT纯合子在抑制优势反应方面也不太有效。我们的研究结果支持多巴胺能变异影响功能障碍性冲动的说法。这与以下观点一致：纹状体DA的过度供应可能会削弱抑制途径，从而增强反应的激活和反应之间的竞争。(C)2010年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Various psychiatric disorders are characterized by elevated levels of impulsivity. Although extensive evidence supports a specific role of striatal, but not frontal dopamine (DA) in human impulsivity, recent studies on genetic variability have raised some doubts on such a role. Importantly, impulsivity consists of two dissociable components that previous studies have failed to separate: functional and dysfunctional impulsivity. We compared participants with a genetic predisposition to have relatively high striatal DA levels (DAT1 9-repeat carriers, DRD2 C957T T/T homozygotes, and DRD4 7-repeat carriers) with participants with other genetic predispositions. We predicted that the first group would show high scores of dysfunctional, but not functional, self-reported impulsivity and greater difficulty in inhibiting a behavioral response to a stop-signal, a behavioral measure of impulsivity. In a sample of 130 healthy adults, we studied the relation between DAT1, DRD4, and C957T polymorphism at the DRD2 gene (polymorphisms related to striatal DA) and catechol-Omethyltransferase (COMT) Val158Met (a polymorphism related to frontal DA) on self-reported dysfunctional and functional impulsivity, assessed by the Dickman impulsivity inventory (DII), and the efficiency of inhibitory control, assessed by the stop-signal paradigm. DRD2 C957T T/T homozygotes and DRD4 7-repeat carriers indeed had significantly higher scores on self-reported dysfunctional, but not functional, impulsivity. TIT homozygotes were also less efficient in inhibiting prepotent responses. Our findings support the claim that dopaminergic variation affects dysfunctional impulsivity. This is in line with the notion that the over-supply of striatal DA might weaken inhibitory pathways, thereby enhancing the activation of, and the competition between responses. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.