Co-occurring ADHD in young children with ASD: Precursors, detection, neural signatures, and early treatment

摘要--自闭症儿童伴发ADHD：先兆、检测、神经特征和 早期治疗 注意缺陷多动障碍(ADHD)发生在40%-60%的自闭症谱系障碍患者中 (ASD)，并在很大程度上导致较差的临床结果。然而，很少有研究关注于 儿童早期自闭症和多动症的重叠。因此，人们对这两种情况是如何共同作用的知之甚少。 在生命中很早就出现。鉴于ASD和ADHD共病的高患病率和临床影响， 杜克大学自闭症卓越中心的总体目标是研究ADHD如何影响共病 早期筛查、神经特征、发育轨迹和对早期治疗的反应 患有自闭症的儿童。项目1将描述共同出现的ADHD症状的危险因素和出现情况 并检查这些症状如何影响早期发现和进展 自闭症患者。这个项目将阐明为什么患有多动症的儿童在较晚的年龄被诊断出来。 并告知更有效的早期检测策略。跟踪接受常规护理的大量幼儿样本 在杜克大学儿科初级诊所(N=约2800名患者/年)，项目1将前瞻性地识别有风险的儿童 并收集有关风险因素、ADHD和发育结果的数据。项目2将阐明共享 和与ASD和ADHD相关的不同神经特征和注意力相关生物标记物，检查 伴发ADHD对自闭症儿童的功能影响，并确定先兆特征 在婴儿期，这预示着以后会出现ASD和ADHD共病。这个项目的特点是 单独患有ASD、ASD+ADHD、单独ADHD的儿童，以及典型的发育中儿童，使用最先进的 方法包括神经生理学、眼球跟踪、运动跟踪和计算机视觉分析。项目 3将评估一种针对ASD+ADHD儿童的个性化早期干预模式 在启动早期行为干预之前，从药物上解决ADHD症状，并确定 行为和神经生理活动的变化可能是治疗反应的基础。这个项目将 通过评估刺激性治疗(Adzenys-XR-ODT)是否增强疗效来实现这些目标 基于早期启动丹佛模式的父母提供的行为干预。这个项目将检查 结果的变化是否与社会注意力的改善相关，通过眼球跟踪来衡量 生物标志物和亲子互动过程中的社会参与。该项目还将审查 行为改善背后的神经生理学变化。这些项目将得到四个项目的支持 核心：行政核心、招聘和评估核心、数据管理和分析核心、 以及传播和外联核心。作为一个整体，杜克大学自闭症卓越中心将 提供迄今为止关于ADHD对患有自闭症的幼儿的影响的最全面的了解， 提供重要的信息，使早期的生物信息和个性化方法成为可能 检测和治疗可以减轻ADHD并存对ASD患者的负面影响。

ABSTRACT – Co-occurring ADHD in young children with ASD: Precursors, detection, neural signatures, and early treatment Attention deficit hyperactivity disorder (ADHD) occurs in ~40-60% of individuals with autism spectrum disorder (ASD) and substantially contributes to poorer clinical outcomes. Yet, very little research has focused on the overlap of ASD and ADHD during early childhood. Thus, little is known about how these two conditions co- emerge early in life. Given the high prevalence and clinical impact of the comorbidity of ASD and ADHD, the overall goal of the Duke Autism Center of Excellence is to characterize how co-occurring ADHD influences early screening, neural signatures, developmental trajectories, and response to early treatment of young children with ASD. Project 1 will characterize risk factors for and emergence of co-occurring ADHD symptoms in young children at risk for ASD and examine how these symptoms influence early detection and progression of ASD. This project will clarify why children who have co-occurring ADHD are diagnosed at a much later age and inform more effective early detection strategies. Following a large sample of toddlers receiving routine care in Duke pediatric primary clinics (N = ~ 2800 patients/year), Project 1 will prospectively identify children at risk for ASD and collect data on risk factors, ADHD, and developmental outcomes. Project 2 will elucidate shared and distinct neural signatures and attention-related biomarkers related to ASD and ADHD, examine the functional impact of co-occurring ADHD in young children with ASD, and identify precursor characteristics during infancy that are predictive of later emergence of comorbid ASD and ADHD. This project will characterize children with ASD alone, ASD+ADHD, ADHD alone, and typically-developing children, using state-of-the-art methods, including neurophysiology, eye-tracking, movement-tracking, and computer vision analysis. Project 3 will evaluate a novel early intervention model personalized for young children with ASD+ADHD that pharmacologically addresses ADHD symptoms prior to initiating early behavioral intervention, and identify changes in behavioral and neurophysiological activity that may underlie response to treatment. This project will accomplish these goals by evaluating whether stimulant treatment (Adzenys-XR-ODT) augments the efficacy of a parent-delivered behavioral intervention based on the Early Start Denver Model. This project will examine whether changes in outcome are correlated with improvements in social attention, measured via eye-tracking biomarkers, and social engagement during parent-child interaction. This project will also examine neurophysiological changes underlying improvements in behavior. These projects will be supported by four cores: Administrative Core, Recruitment and Assessment Core, Data Management and Analysis Core, and Dissemination and Outreach Core. Functioning as a whole, the Duke Autism Center of Excellence will offer the most comprehensive understanding to date of the impact of ADHD on young children with ASD, providing important information that will allow for biologically informed and personalized methods for early detection and treatment that could mitigate the negative impact of co-occurring ADHD on individuals with ASD.