谷氨酸突触发育通路参与神经发生与迁移、突触形成与可塑性、轴突导向以及神经元活动调节等过程，在注意缺陷多动障碍（ADHD）的发生过程中起重要作用。我们首先采用多中心两阶段的病例对照研究策略，对谷氨酸突触发育通路关键基因（LPHN3、FLRT3、GRM5、GRM7、GRIN2A、GRIN2B、GRIN1、GRID2、GRIK1、GRIK4和SLC1A3）的遗传变异与ADHD发生的关系进行全面分析，重点探讨基因-基因、基因-环境相互作用对疾病易感性的影响；同时结合分子生物学和细胞生物学技术手段，深入探讨与ADHD易感性相关的遗传变异的生物学机制；并对鉴定出的与ADHD关联的风险基因，应用静息态功能磁共振成像技术探讨风险基因的神经影像学效应，从神经生物学机制阐明ADHD的发病机理。所识别的与ADHD易感性相关的遗传变异可作为遗传标记物用于ADHD高风险个体的筛查和预后监测。

Glutamatergic synapse development pathway, which plays an important role in the process of neuronal growth and migration, synapse formation and plasticity, axon guidance and the regulation of neuron activity, may be involved in the development of attention deficit hyperactivity disorder(ADHD). A comprehensive analysis, including two independent case-control studies and biological mechanism assays, will be conducted to detect the association between the genetic variations of key genes（LPHN3, FLRT3, GRM5, GRM7, GRIN2A, GRIN2B, GRIN1, GRID2, GRIK1, GRIK4 and SLC1A3）in the glutamatergic synapse development pathway and risk of ADHD, especially the roles of gene-gene and gene-environment interactions. We also use resting-state functional magnetic resonance imaging to illuminate the neuroimaging effects of risk genes. A combination of methods in molecular biology, cytobiology and neuroimaging is used to clarify the pathogenesis of ADHD. The identified genetic variations may be used as genetic biomarkers in the future for the screening and prognosis surveillance in the high-risk groups.