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

摘要：ASD幼儿中并发ADHD：前驱体、检测、神经特征和 早期治疗 注意力缺陷多动障碍（ADHD）发生在约40 - 60%的自闭症谱系障碍患者中 (ASD)并且实质上导致较差的临床结果。然而，很少有研究集中在 ASD和ADHD在儿童早期的重叠。因此，很少有人知道这两个条件是如何共同的。 在生命的早期出现。鉴于ASD和ADHD合并症的高患病率和临床影响， 杜克自闭症卓越中心的总体目标是描述同时发生的ADHD如何影响 早期筛查，神经特征，发育轨迹，以及对早期治疗的反应 ASD儿童项目1将描述并发ADHD症状的风险因素和出现 研究这些症状如何影响早期发现和进展 的ASD。这个项目将澄清为什么儿童谁共同发生多动症是在诊断年龄晚得多 并提供更有效的早期检测策略。在大量接受常规护理的幼儿样本中， 在杜克儿科初级诊所（N =~2800例患者/年），项目1将前瞻性识别风险儿童 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 以及与ASD和ADHD相关的不同神经特征和注意力相关生物标志物，检查 ASD幼儿合并ADHD的功能影响，并确定前驱特征 在婴儿期，可以预测ASD和ADHD共病的后期出现。该项目将以 单独ASD、ASD + ADHD、单独ADHD和典型发育儿童，使用最先进的 方法，包括神经生理学，眼睛跟踪，运动跟踪和计算机视觉分析。项目 3将评估一种针对ASD + ADHD幼儿的个性化早期干预模式， 在开始早期行为干预之前，注意力缺陷多动症的症状，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。该项目将 通过评估兴奋剂治疗（Adzenys-XR-ODT）是否增强疗效来实现这些目标 一个基于早期启动丹佛模型的父母提供的行为干预。该项目将研究 结果的变化是否与通过眼动追踪测量的社会注意力的改善相关 生物标志物和亲子互动期间的社会参与。该项目还将研究 行为改善的神经生理学变化。这些项目将得到四个 核心：行政核心，招聘和评估核心，数据管理和分析核心， 传播和外联核心。作为一个整体，杜克自闭症卓越中心将 提供迄今为止最全面的了解ADHD对ASD幼儿的影响， 提供重要的信息，这将允许生物信息和个性化的方法， 检测和治疗，可以减轻并发ADHD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.