Dopamine Transporter (SLC6A3) Genotype Impacts Neurophysiological Correlates of Cognitive Response Control in an Adult Sample of Patients with ADHD
Dopamine Transporter (SLC6A3) Genotype Impacts Neurophysiological Correlates of Cognitive Response Control in an Adult Sample of Patients with ADHD
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DOI：
10.1038/npp.2010.91
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发表时间：
2010-10-01
影响因子：
7.6
通讯作者：
Fallgatter, Andreas J.
中科院分区：
文献类型：
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作者：
Dresler, Thomas;Ehlis, Ann-Christine;Fallgatter, Andreas J.
研究为注意力缺陷多动障碍（ADHD）的多巴胺能神经传递功能障碍提供了充分的证据。在这方面，多巴胺转运蛋白基因（SLC 6A 3）的3 '非翻译区（UTR）中常见的串联重复序列（VNTR）多态性与该疾病反复相关。在这里，我们研究了SLC 6A 3常见的9-和10-重复等位基因对大样本成人ADHD患者（n = 161）和健康对照（n = 109）的前额叶脑功能和认知反应控制的影响。为此，我们检查了认知反应控制的神经生理标志物（NoGo前化，NGA）引起的Go-NoGo任务（连续性能测试，CPT）。在ADHD患者组中，9个重复等位基因携带者的NGA显著降低，而在对照组中没有观察到SLC 6A 3基因型的影响。与以前的儿童相关研究相反，在我们的成人ADHD患者样本中，9个重复而不是10个重复的等位基因与功能障碍相关。我们的研究结果证实了SLC 6A 3基因型对ADHD认知反应控制的神经生理学相关性的显著影响，并表明仍有待确定的年龄相关因素是调节遗传因素对内表型影响的重要变量。Neuropsychopharmacology（2010）35，2193-2202; doi：10.1038/npp.2010.91; 2010年7月14日在线发表
Studies provide ample evidence for a dysfunction in dopaminergic neurotransmission in Attention-Deficit/Hyperactivity Disorder (ADHD). In that respect, a common variable number of tandem repeats (VNTR) polymorphism in the 3'untranslated region (UTR) of the dopamine transporter gene (SLC6A3) has been repeatedly associated with the disorder. Here, we examined the influence of the common 9- and 10-repeat alleles of SLC6A3 on prefrontal brain functioning and cognitive response control in a large sample of adult ADHD patients (n = 161) and healthy controls (n 109). To this end, we inspected a neurophysiological marker of cognitive response control (NoGo anteriorization, NGA) elicited by means of a Go-NoGo task (continuous performance test, CPT). Within the group of ADHD patients, nine-repeat allele carriers showed significantly reduced NGA, whereas no influence of SLC6A3 genotype was observed in the control group. In contrast to previous association studies of children, the nine-repeat-not the 10-repeat-allele was associated with functional impairments in our sample of adult ADHD patients. Our findings confirm a significant effect of the SLC6A3 genotype on the neurophysiological correlates of cognitive response control in ADHD, and indicate that still to-be-identified age-related factors are important variables modulating the effect of genetic factors on endophenotypes. Neuropsychopharmacology (2010) 35, 2193-2202; doi:10.1038/npp.2010.91; published online 14 July 2010