Stratifying the Heterogeneity of Autism Spectrum Disorder: Impact of Co-Occurring Anxiety and ADHD

摘要 自闭症谱系障碍(Asd)的本质异质性是早期诊断和发展的关键障碍。 以及评估治疗这种疾病的有效方法。虽然早期的行为干预针对的是社交， 认知和适应功能改善了许多ASD儿童的预后，在 研究范围内的治疗反应。考虑到这种差异，对ASD的异质性进行分层对于识别 生物标志物，帮助提供者系统地诊断、量身定做治疗和监测反应。拟议中的项目 通过阐明这种异质性的一个潜在关键来源的影响来回应这一关键需求：共生 焦虑和多动症。关于焦虑症和多动症的独特和相加的影响，我们知之甚少。 儿童早期自闭症患者。此外，这些共生疾病对 常用的神经和行为生物标记物在目前的文献中仍然是一个空白。要填补这些空白， 文献中，我们提出了一种多模式方法，使用父母报告、观察性评估、 和神经生理学分析，对来自4个组的幼儿样本进行仔细的表型分析：仅有ASD， ASD+焦虑、ASD+ADHD、ASD+焦虑+ADHD。我们的中心假设是共病焦虑或ADHD 将对临床表现、执行功能和生物标志物产生独特的和相加的影响 患有自闭症的幼儿的签名。为了检验这一假设，我们有三个目的：(1)区分 自闭症幼儿的核心焦虑或多动症及其相关症状。(2)识别 自闭症患儿伴发焦虑或ADHD与执行功能缺陷的关系。(3) 确定共同发生的焦虑或ADHD与神经、注意力和行为的关系 生物标记物被用来描述和监测ASD的治疗。如果成功，这个项目将提供更好的 了解ADHD和焦虑症共存对临床表现、功能结果、 和ASD的神经生物学。这反过来将提高我们将患有自闭症的幼儿分层为有意义的 子组。这一知识将支持开发有效的和生物学上了解情况的方法来早期 检测和治疗，可以减轻ADHD和焦虑共存对长期的负面影响 自闭症患者的转归。

ABSTRACT The substantial heterogeneity in autism spectrum disorder (ASD) is a key barrier in early diagnosis and in developing and evaluating effective treatments for the disorder. Although early behavioral intervention targeting social, cognitive, and adaptive functioning improves outcomes for many children with ASD, there is significant variability in treatment response within studies. Given this variation, stratifying the heterogeneity of ASD is essential for identifying biomarkers to help providers systematically diagnose, tailor treatment, and monitor response. The proposed project responds to this critical need by elucidating the impact of a potential key source of this heterogeneity: co-occurring anxiety and ADHD. Little is known about the unique and additive impacts of co-occurring anxiety and ADHD on individuals with autism in the early childhood period. Furthermore, the impact of these co-occurring disorders on commonly used neural and behavioral biomarkers remains a gap in the current literature. To fill these gaps in the literature, we propose a multimodal approach, using a combination of parent reports, observational assessments, and neurophysiological assays, to carefully phenotype samples of young children from 4 groups: ASD alone, ASD+Anxiety, ASD+ADHD, and ASD+Anxiety+ADHD. Our central hypothesis is that co-occurring anxiety or ADHD will have both unique and additive effects on the clinical presentation, executive functioning, and biomarker signatures of young children with ASD. To test this hypothesis, we have three aims: (1) Differentiate the impact of co-occurring anxiety or ADHD on core and associated symptoms in young children with ASD. (2) Identify the relationship between co-occurring anxiety or ADHD and executive function deficits in young children with ASD. (3) Determine the relationship between co-occurring anxiety or ADHD and neural, attentional, and behavioral biomarkers being used to characterize and monitor treatments in ASD. If successful, this project will provide a better understanding of the impact of co-occurring ADHD and anxiety on the clinical presentation, functional outcomes, and neurobiology of ASD. This in turn will improve our ability to stratify young children with ASD into meaningful subgroups. This knowledge will support development of effective and biologically informed methods for early detection and treatment, which can mitigate the negative effects of co-occurring ADHD and anxiety on long-term outcomes of individuals with ASD.