孤独症谱系障碍与注意缺陷多动障碍疾病特异性及共同神经病理缺陷的多模态磁共振研究

Autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD) are both severely impairing neurodevelopmental disorders in clinical practice. Although the core symptoms of these two disorders are different, they have high comorbidity rate, partly shared executive function deficits and heritability, which suggest they may have disease/symptom-specific and common neurobiological basis underlying these two disorders. However, few studies have compared the two disorders directly to elucidate the disease-specific and shared underlying neurobiological biomarkers using multimodal magnetic resonance imaging (MRI) technology. In this cross-sectional study, we plan to explore the disease/symptom-specific and shared brain structural and functional alterations in ASD and ADHD from both diagnostic categories and symptom dimensional perspectives using multimodal MRI technology. We will recruit four groups, i.e. pure ASD, pure ADHD, comorbid ASD and ADHD (ASD+ADHD) and healthy controls, each group includes 40 participants with age, gender and handedness matched on group level. We will conduct the following analysis: (1) disease-brain relationships analysis: We will compare the disease-specific and shared brain structural and functional abnormalities between ASD and ADHD based on diagnostic categories, and then validate these findings in ASD+ADHD group. (2) behavior-brain relationship analysis: We will explore the correlation between ASD and ADHD symptoms and brain measures in a continuum symptoms spectrum group including healthy controls, ADHD, ASD and ASD+ADHD participants from a dimensional perspective. The results of this study will contribute to our understanding of the disease/symptom-specific biomarkers and common pathophysiology in these two related disorders, help to identify diagnostic and differential diagnostic biomarkers for these two disorders, and add to the empirical evidences for common and targeted therapy for ASD and ADHD.

孤独症谱系障碍（ASD）与注意缺陷多动障碍（ADHD）是临床常见的神经发育障碍，患病率逐年增高，预后不良，需要正确诊断、积极干预以改善预后。虽然ASD和ADHD核心症状表现不同，但临床共患率高，存在疾病特异及共同的执行功能缺陷及遗传基础，推测两种障碍存在特异及共同的神经病理机制，目前尚缺乏直接比较的多模态磁共振研究。本项目采用横断面研究，选取ASD、ADHD、ASD共患ADHD及正常对照共四组受试，每组40例，从疾病分类学角度，比较两种障碍的疾病特异及共同的脑结构及功能缺陷，探讨疾病-脑之间的关系；从症状维度学角度，寻找与ASD和ADHD两组症状存在特异及共同相关的脑特征，探讨行为-脑之间的关系。研究结果对于从疾病分类和症状维度两种不同的角度深入理解神经发育障碍的病理机制，寻找ASD与ADHD特异及共同的神经病理缺陷，提高疾病的精准诊断，针对共同缺陷的靶脑区设计共同干预方法具有重要的意义。

孤独症谱系障碍（ASD）与注意缺陷多动障碍（ADHD）均是起病于童年期的神经发育障碍。此两种障碍共患率高，症状表现常相互掩盖，容易造成疾病的误诊及漏诊，为临床诊疗带来了困难，需要寻找ASD和ADHD各自特异性的神经生物学标记物，以利于疾病的精准诊疗。本项目采用横断面研究，在严格诊断（根据半定式访谈工具诊断）的基础上，共收集完整数据166例（包括一般人口学资料、临床及影像学数据），其中ADHD组46例， ASD组38例，ASD共患ADHD组40例，正常对照组42例，四组被试的年龄、性别、智商相匹配。我们分别对两类障碍的认知功能、神经影像学数据以及遗传数据进行分析，主要研究结果包括（1）采用各向异性效应尺寸符号差分映射（AES-SDM）和激活似然估计（ALE）方法的Meta分析发现，ADHD和ASD共同存在胼胝体的异常，但ADHD组胼胝体压部的各向异性（FA）降低，ASD组胼胝体膝部和压部FA降低，并且从儿童到成年期，这两种障碍胼胝体束异常持续存在，且胼胝体束异常的重叠区域随年龄增长而增加；（2）通过对ADHD进行动态及静态大脑功能连接分析发现，腹外侧前额叶可能是ADHD的关键脑区，进一步多变量风险评分（PRS）显示NRXN1基因变异通过调节感觉运动回路的功能从而增加了ADHD的风险；（3）通过对ASD的脑结构及脑功能分析发现，ASD患者在儿童期、青春期和成年期表现出异常的灰质体积变化，但各个年龄段异常变化不同，提示做ASD神经影像学研究时需要考虑被试的年龄因素。总之，我们收集了完整的ASD、ADHD以及ASD共患ADHD组的数据，多维度、较全面地探讨了ASD与ADHD的疾病特征，发现了ASD及ADHD共同及特异性受损的脑机制，为深入理解ASD与ADHD共同及特异的神经机制提供了证据。