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[注意缺陷多动障碍(ADHD)的遗传学研究结果]

[Genetic findings in Attention-Deficit and Hyperactivity Disorder (ADHD)].

作者信息

Schimmelmann Benno Graf, Friedel Susann, Christiansen Hanna, Dempfle Astrid, Hinney Anke, Hebebrand Johannes

机构信息

Klinik für Psychiatrie und Psychotherapie des Kindes- und Jugendalters, Universität Duisburg-Essen, Rheinische Kliniken Essen, Virchowstrasse 174, DE-45147 Essen.

出版信息

Z Kinder Jugendpsychiatr Psychother. 2006 Nov;34(6):425-33. doi: 10.1024/1422-4917.34.6.425.

Abstract

Attention-Deficit and Hyperactivity Disorder (ADHD) is a common child and adolescent psychiatric disorder with a prevalence rate of 3-7%. Formal genetic studies provided an estimated heritability of 0.6-0.8 and an approximately five-fold elevated risk for ADHD in first-degree relatives. Currently, four genome scans have led to the identification of chromosomal regions potentially relevant in ADHD; especially the evidence for linkage to chromosome 5p13 is convincing. Meta-analyses of a large number of candidate gene studies suggest association with gene variants of the dopaminergic receptors DRD4 and DRD5, the serotonergic receptor HTR1B, and the synaptosomal receptor protein (SNAP-25). Hyperactivity has been investigated particularly in animal models, focusing on knockout- and quantitative trait loci (QTL) designs, with promising results for the dopaminergic system. It is likely that several gene polymorphisms with moderate to small effect sizes contribute to the phenotype ADHD; different combinations of such predisposing variants presumably underlie ADHD in different individuals. Therefore, large samples for molecular genetic studies are mandatory to detect these polymorphisms. Accordingly, several of today's findings have to be regarded as preliminary. The understanding of ADHD's neurobiology may be advanced by new technologies, such as SNP-based genome scans performed with gene chips comprising 10,000-1,000,000 SNPs, as well as using more sophisticated animal model designs.

摘要

注意力缺陷多动障碍(ADHD)是一种常见的儿童和青少年精神疾病,患病率为3%-7%。正式的遗传学研究表明,其遗传度估计为0.6-0.8,一级亲属患ADHD的风险大约高出五倍。目前,四项全基因组扫描已确定了与ADHD潜在相关的染色体区域;特别是与5号染色体p13区域连锁的证据很有说服力。大量候选基因研究的荟萃分析表明,多巴胺能受体DRD4和DRD5、血清素能受体HTR1B以及突触体相关蛋白(SNAP-25)的基因变异与之有关。多动问题尤其在动物模型中得到了研究,重点是基因敲除和数量性状基因座(QTL)设计,对多巴胺能系统取得了有前景的结果。可能有几种效应大小为中等至小的基因多态性促成了ADHD的表型;这些易感变异的不同组合可能是不同个体患ADHD的基础。因此,进行分子遗传学研究需要大样本以检测这些多态性。相应地,当今的一些发现必须被视为初步的。新技术,如使用包含10000-1000000个单核苷酸多态性(SNP)的基因芯片进行基于SNP的全基因组扫描,以及采用更复杂的动物模型设计,可能会推动对ADHD神经生物学的理解。

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