Thapar Anita, Stergiakouli Evangelia
Department of Psychological Medicine, School of Medicine, Cardiff University, United Kingdom.
Xin Li Xue Bao. 2008 Aug;40(10):1088-1098. doi: 10.3724/SP.J.1041.2008.01088.
Attention Deficit Hyperactivity is a childhood-onset disorder that can persist into adult life. Traditional family, twin and adoption studies have shown that ADHD defined both categorically and dimensionally is familial and heritable. Twin studies are now being used to examine ways of defining the ADHD phenotype, to investigate gender differences, the effects on genes on continuity and comorbidity and to consider gene-environment interplay. Molecular genetic findings on ADHD have mainly arisen from functional candidate gene association studies and a number of pooled and meta-analyses have now been conducted. There is consistent evidence of association between ADHD and a dopamine D4 receptor gene VNTR and a dopamine D5 receptor gene microsatellite marker. More recent evidence from different studies and a pooled analysis suggests that conduct problems in those with ADHD is influenced by the COMT val158/108 met variant. Linkage studies suggest that there are no genes of moderate effect size and findings from large scale whole genome association studies are currently awaited. Overall the evidence to date, suggests that examining gene-phenotype links and testing whether gene variants have modifying effects on the ADHD phenotype are important. The contribution of gene-environment interplay (G x E) to psychopathology is becoming increasingly recognised, although for ADHD little is known on causal environmental risk factors.
注意缺陷多动障碍是一种始于儿童期的疾病,可持续至成年期。传统的家庭、双胞胎和收养研究表明,无论是按类别还是维度定义的注意力缺陷多动障碍都具有家族遗传性。目前,双胞胎研究正被用于研究定义注意力缺陷多动障碍表型的方法、调查性别差异、基因对连续性和共病的影响以及考虑基因与环境的相互作用。关于注意力缺陷多动障碍的分子遗传学研究结果主要来自功能性候选基因关联研究,目前已经进行了一些汇总分析和荟萃分析。有一致的证据表明,注意力缺陷多动障碍与多巴胺D4受体基因VNTR和多巴胺D5受体基因微卫星标记之间存在关联。来自不同研究和汇总分析的最新证据表明,注意力缺陷多动障碍患者的行为问题受儿茶酚-O-甲基转移酶(COMT)val158/108 met变异体的影响。连锁研究表明,不存在效应大小适中的基因,目前正在等待大规模全基因组关联研究的结果。总体而言,迄今为止的证据表明,研究基因与表型的联系以及测试基因变异体是否对注意力缺陷多动障碍表型有修饰作用很重要。尽管对于注意力缺陷多动障碍,人们对因果环境风险因素知之甚少,但基因与环境相互作用(G×E)对精神病理学的贡献正越来越受到认可。