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注意缺陷多动障碍的神经心理学内表型:遗传关联研究综述。

Neuropsychological endophenotypes in attention-deficit/hyperactivity disorder: a review of genetic association studies.

机构信息

INSERM, U894, University Paris Descartes, Paris, France.

出版信息

Eur Arch Psychiatry Clin Neurosci. 2011 Dec;261(8):583-94. doi: 10.1007/s00406-011-0207-5. Epub 2011 Mar 16.

Abstract

As a relatively large body of research has been published up to now, it may be informative to explore whether the use of endophenotypes has produced consistent findings in attention-deficit hyperactivity disorder (ADHD). We reviewed the results of genetic studies investigating associations between putative susceptibility genes for ADHD and neuropsychological traits relevant for this disorder. A PubMed database search identified 47 studies. Most of them (n = 36) examined a single candidate gene, while seven studies examined two or three genes and only four studies examined 10 genes or more. The most investigated genes were DRD4, DAT1, COMT, MAOA, and DBH. Regarding DRD4, association of high reaction time variability with the 7-R allele absence appears to be the most consistent result. Speed of processing, set shifting, and cognitive impulsiveness were less frequently investigated, but seem to be altered in the 7-R allele carriers. Regarding DAT1, majority of studies reported negative results indicating that this gene may have a modulating effect rather than direct influence on cognitive functioning. The other genes were investigated in fewer studies, and the reported findings need to be replicated. The principal methodological issues that could represent confounding factors and may explain conflicting results are discussed.

摘要

迄今为止,已经有相当数量的研究发表,因此,探讨内表型的使用是否在注意力缺陷多动障碍(ADHD)中产生了一致的发现可能是有意义的。我们回顾了遗传研究的结果,这些研究调查了 ADHD 的潜在易感基因与该疾病相关的神经心理学特征之间的关联。在 PubMed 数据库中进行搜索,确定了 47 项研究。其中大多数(n=36)研究了单个候选基因,而 7 项研究研究了两个或三个基因,只有 4 项研究研究了 10 个或更多基因。研究最多的基因是 DRD4、DAT1、COMT、MAOA 和 DBH。关于 DRD4,高反应时变异性与 7-R 等位基因缺失的关联似乎是最一致的结果。加工速度、转换和认知冲动性的研究较少,但在 7-R 等位基因携带者中似乎发生了改变。关于 DAT1,大多数研究报告了阴性结果,表明该基因可能具有调节作用,而不是对认知功能有直接影响。其他基因的研究较少,需要对报告的结果进行复制。讨论了可能代表混杂因素并可能解释冲突结果的主要方法学问题。

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