Genetics of preparation and response control in ADHD: the role of DRD4 and DAT1
Genetics of preparation and response control in ADHD: the role of DRD4 and DAT1
复制标题
DOI：
10.1111/jcpp.12212
复制
发表时间：
2014-08-01
影响因子：
7.6
通讯作者：
Banaschewski, Tobias
中科院分区：
文献类型：
--
作者：
Albrecht, Bjoern;Brandeis, Daniel;Banaschewski, Tobias
背景资料：与注意力定向（Cue-P3），认知或反应准备（Cue-CNV）和抑制反应控制（Nogo-P3）相关的表现和大脑活动的困难在任务开发执行功能中是ADHD的家族性疾病，可能代表内表型。本研究的目的是阐明多巴胺受体D4（DRD 4）和多巴胺转运蛋白（DAT 1）基因多态性对ADHD和对照儿童这些过程的影响。研究方法：行为和电生理参数从线索连续性能测试与低和高注意力负荷进行了评估，在男孩与ADHD组合型（N = 94）和对照组没有ADHD家族史（N = 31）。这两组被分为至少一个DRD 4 7-重复等位基因和DAT 1 10-6单倍型的存在。结果：ADHD儿童表现为操作能力下降，Cue-P3、CNV和Nogo-P3波幅降低。DRD 4 7 R儿童表现出类似的表现问题和较低的Cue-P3和CNV，但Nogo-P3没有减少。DAT 1 10-6单倍型的儿童在表现或提示P3和CNV方面没有困难，但与预期相反，Nogo-P3增加。没有基因型与ADHD的相互作用。结论：这项研究检测了DRD 4 7 R对与注意力定向和反应准备相关的表现和大脑活动的特定影响，而DAT 1 10-6与抑制反应控制相关的大脑活动升高相关，这可能补偿增加的冲动。由于这些基因型效应对ADHD的影响是加性的，因此目前的结果表明，DRD 4和DAT 1多态性是ADHD的功能相关风险因素，并且可能是共享这些内表型的其他疾病。
Background: Difficulties with performance and brain activity related to attentional orienting (Cue-P3), cognitive or response preparation (Cue-CNV) and inhibitory response control (Nogo-P3) during tasks tapping executive functions are familial in ADHD and may represent endophenotypes. The aim of this study was to clarify the impact of dopamine receptor D4 (DRD4) and dopamine transporter (DAT1) gene polymorphisms on these processes in ADHD and control children. Methods: Behavioural and electrophysiological parameters from cued continuous performance tests with low and high attentional load were assessed in boys with ADHD combined type (N = 94) and controls without family history of ADHD (N = 31). Both groups were split for the presence of at least one DRD4 7-repeat allele and the DAT1 10-6 haplotype. Results: Children with ADHD showed diminished performance and lower Cue-P3, CNV and Nogo-P3 amplitudes. Children with DRD4 7R showed similar performance problems and lower Cue-P3 and CNV, but Nogo-P3 was not reduced. Children with the DAT1 10-6 haplotype had no difficulties with performance or Cue-P3 and CNV, but contrary to expectations increased Nogo-P3. There were no Genotype by ADHD interactions. Conclusions: This study detected specific effects of DRD4 7R on performance and brain activity related to attentional orienting and response preparation, while DAT1 10-6 was associated with elevated brain activity related to inhibitory response control, which potentially compensates increased impulsivity. As these genotype effects were additive to the impact of ADHD, the current results indicate that DRD4 and DAT1 polymorphisms are functionally relevant risk factors for ADHD and presumably other disorders sharing these endophenotypes.