注意缺陷多动障碍（ADHD）是神经发育障碍性疾病，其遗传度约为0.76。国内外多项GWAS研究尚未发现达全基因组水平显著关联的常见变异；本课题组前期外显子芯片结果提示与神经发育及突触功能相关的细胞粘附分子CADM1基因的遗传变异可能与ADHD关联，该基因在大脑前额叶的表达水平最高。本研究为探讨CADM1基因在ADHD发病机制中的作用，拟1）在独立样本中（汉族ADHD与对照各1500例）进行遗传关联分析，验证CADM1基因遗传变异与ADHD临床表型的关联；2）采用“基因-神经影像-神经心理”策略，探讨CADM1基因与ADHD前额叶结构/功能及其执行功能（抑制、工作记忆和转换）的关联，初步阐释其参与ADHD发病的作用机制。本项目预期从神经发育角度确定ADHD易感基因，为ADHD的致病机制提供分子遗传学及脑科学证据；发现基因特异性的执行功能、脑结构和功能模式，为ADHD的早期诊断提供生物学标记。

Attention-deficit/hyperactivity disorder (ADHD) is one of the common neurodevelopmental disorders with high reported heritability of approximately 0.76. Genome-wide association studies (GWAS) have failed to find a major common variant for ADHD, however, our preliminary results from exome chip implicated CADM1 gene with high expression in prefrontal cortex might be involved in the pathophysiology of ADHD. CADM1 gene may play an important role in neurodevelopment and synaptic function. This project will replicate the association between CADM1 and ADHD in an independent sample including 1,500 ADHD and 1,500 controls. In addition, the “genetic-neuroimagical-neuropsychological” strategy will follow to illustrate the effect of CADM1 gene on the structure and function of prefrontal cortex as well as executive function (including inhibition, working memory and shifting). We anticipate finding the target biological marker for early diagnosis from a neurodevelopmental perspective, also further facilitate a potentially genetic, neuroimagical and neuropsychological framework for the aetiopathogenesis of ADHD.