在近年来的注意缺陷多动障碍（ADHD）研究中，情绪失调逐渐得到广泛的关注。情绪失调被认为是ADHD的重要临床特征，并可能是其症状核心成分。ADHD情绪失调的遗传度约为0.72，提示遗传因素的重要作用。单胺系统基因多态可能参与ADHD情绪失调，需进一步研究，并明确其作用的脑机制。本研究拟对1500例ADHD儿童及500名正常对照儿童评估情绪失调症状，检测单胺系统基因多态，通过关联分析寻找ADHD情绪失调的遗传易感因素；同时结合前期的影像学发现，基于“前额叶-杏仁核”环路的静息态脑功能连接，分析遗传易感因素与异常连接指征的关联，探讨单胺系统基因多态通过前额叶-杏仁核环路影响ADHD情绪失调的脑机制。

Recently, emotional dysregulation (ED) has attracted more and more attention in the studies of attention-deficit/hyperactivity disorder (ADHD). ED has been suggested to be a core component of ADHD in its conceptualization and diagnostic criteria. A recent study indicated the high heritability of ED in ADHD at about 0.72, suggesting the important role of genetic factors in its pathogenesis. Monoaminergic genes have been suggested to be involved in the etiology of ED in ADHD. However, more researches are needed to explore the mechanism of the risk genetic variants. In the current project, we firstly evaluate the ED symptoms of 1500 ADHD children and 500 normal control children, detect the genotypes of monoaminergic genes, and then conduct genetic analyses to find the genetic risk factors for ED in ADHD. Secondly, based on our previous finding, we set the resting-state function of prefrontal-amygdala circuit as a key imaging feature and study the association of the above genetic risk factors with the abnormal imaging features to explore the brain mechanism of these risk genetic variants.

情绪失调是注意缺陷多动障碍（ADHD）核心症状外的重要相关特征，可能是其症状的固有、核心成分。本项目在前期研究的基础上，采用影像遗传学策略，探讨遗传易感因素通过影响情绪相关脑环路“前额叶-杏仁核”的功能导致ADHD情绪失调的机制。具体结果如下：（1）本项目首先在大样本中对ADHD情绪失调的特征进行了深入的刻画，结果显示性别、智商对情绪失调症状严重程度无影响，ADHD-混合型（C）及共患ODD的儿童情绪失调症状更重。ADHD儿童情绪失调症状随年龄增长呈现出“稳定、持续”的状态，与正常对照儿童的“下降”轨迹不同；情绪失调症状能够很好的预测ADHD诊断，对临床筛查和隐匿性ADHD的发现具有重要意义；（2）除了单胺类神经递质系统基因，我们将遗传检测扩展到全基因组，结果发现ITGA1基因与ADHD存在关联，同时与ADHD儿童生态执行功能存在关联，包括情绪调控因子；（3）“前额叶-杏仁核”环路静息态功能连接与ADHD情绪失调症状存在关联，我们进一步分析了DTI数据，结果发现ADHD大脑白质微结构的异常可能参与ADHD情绪失调的发生，包括前辐射冠等；（4）对遗传因素的脑机制进行探讨有助于我们更深入的了解ADHD情绪失调的病因。我们结合基因检测数据和脑影像指标进行分析，结果发现去甲肾上腺素系统基因交互作用（NET1基因rs3785143位点与DBH基因rs1611115位点）可能通过影响“前额叶-杏仁核”的静息态功能连接导致ADHD情绪失调的发生发展，同时携带两个位点危险等位基因的儿童，其负性功能连接更弱。