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.

译文

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%。正式的遗传研究提供了0.6-0.8的估计遗传力,一级亲属的ADHD风险增加了大约五倍。目前,四次基因组扫描已导致鉴定与ADHD潜在相关的染色体区域; 尤其是与5p13染色体连锁的证据令人信服。对大量候选基因研究的荟萃分析表明,与多巴胺能受体DRD4和DRD5,血清素能受体HTR1B和突触体受体蛋白 (SNAP-25) 的基因变异有关。特别是在动物模型中研究了多动症,重点是敲除和数量性状基因座 (QTL) 设计,并为多巴胺能系统带来了可喜的结果。几种具有中等至小效应大小的基因多态性可能会导致ADHD表型; 这种易感变异的不同组合可能是不同个体ADHD的基础。因此,用于分子遗传学研究的大样本必须检测这些多态性。因此,今天的一些发现必须被视为初步的。对ADHD的神经生物学的理解可以通过新技术来推进,例如使用包含10,000 1,000,000 SNP的基因芯片进行的基于SNP的基因组扫描,以及使用更复杂的动物模型设计。

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