Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim, Germany.
Eur Child Adolesc Psychiatry. 2010 Mar;19(3):237-57. doi: 10.1007/s00787-010-0090-z. Epub 2010 Feb 10.
As heritability is high in attention-deficit/hyperactivity disorder (ADHD), genetic factors must play a significant role in the development and course of this disorder. In recent years a large number of studies on different candidate genes for ADHD have been published, most have focused on genes involved in the dopaminergic neurotransmission system, such as DRD4, DRD5, DAT1/SLC6A3, DBH, DDC. Genes associated with the noradrenergic (such as NET1/SLC6A2, ADRA2A, ADRA2C) and serotonergic systems (such as 5-HTT/SLC6A4, HTR1B, HTR2A, TPH2) have also received considerable interest. Additional candidate genes related to neurotransmission and neuronal plasticity that have been studied less intensively include SNAP25, CHRNA4, NMDA, BDNF, NGF, NTF3, NTF4/5, GDNF. This review article provides an overview of these candidate gene studies, and summarizes findings from recently published genome-wide association studies (GWAS). GWAS is a relatively new tool that enables the identification of new ADHD genes in a hypothesis-free manner. Although these latter studies could be improved and need to be replicated they are starting to implicate processes like neuronal migration and cell adhesion and cell division as potentially important in the aetiology of ADHD and have suggested several new directions for future ADHD genetics studies.
由于注意缺陷多动障碍(ADHD)的遗传性很高,遗传因素在这种疾病的发展和病程中必须发挥重要作用。近年来,已经发表了大量关于 ADHD 不同候选基因的研究,其中大多数集中在涉及多巴胺能神经传递系统的基因上,如 DRD4、DRD5、DAT1/SLC6A3、DBH、DDC。与去甲肾上腺素能(如 NET1/SLC6A2、ADRA2A、ADRA2C)和 5-羟色胺能系统(如 5-HTT/SLC6A4、HTR1B、HTR2A、TPH2)相关的基因也受到了相当大的关注。与神经传递和神经元可塑性相关的其他候选基因的研究也相对较少,包括 SNAP25、CHRNA4、NMDA、BDNF、NGF、NTF3、NTF4/5、GDNF。本文综述了这些候选基因的研究,并总结了最近发表的全基因组关联研究(GWAS)的结果。GWAS 是一种相对较新的工具,能够以无假设的方式识别新的 ADHD 基因。尽管这些后续研究可以得到改进,并且需要进行复制,但它们开始暗示神经元迁移和细胞黏附和细胞分裂等过程可能对 ADHD 的发病机制很重要,并为未来的 ADHD 遗传学研究提出了几个新的方向。