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

摘要 自闭症谱系障碍（ASD）的实质异质性是早期诊断和发展的关键障碍。 并评估有效的治疗方法。虽然早期行为干预针对社会， 认知和适应功能改善了许多ASD儿童的结果， 研究中的治疗反应。鉴于这种差异，对ASD的异质性进行分层对于识别 生物标志物，以帮助供应商系统地诊断，定制治疗和监测反应。拟建项目 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： 焦虑和多动症关于共同发生的焦虑和ADHD对儿童的独特和附加影响， 患有自闭症的人在幼儿期。此外，这些共同发生的疾病对 在目前的文献中，常用的神经和行为生物标志物仍然是一个空白。为了填补这些空白， 文献，我们提出了一种多模式的方法，使用家长报告，观察评估， 和神经生理学测定，仔细表型的幼儿样品从4组：单独的ASD， ASD+焦虑，ASD+ADHD，ASD+焦虑+ADHD。我们的核心假设是，共同发生的焦虑或多动症 将对临床表现、执行功能和生物标志物产生独特和叠加效应 自闭症儿童的签名。为了验证这一假设，我们有三个目标：（1）区分 ASD幼儿中核心和相关症状的共发焦虑或ADHD。(2)识别 ASD幼儿中并发焦虑或ADHD与执行功能缺陷之间的关系（三） 确定共同发生的焦虑或ADHD与神经，注意力和行为之间的关系 用于表征和监测ASD治疗的生物标志物。如果成功，这个项目将提供一个更好的 了解共患ADHD和焦虑对临床表现，功能结局， 和神经生物学的研究这反过来将提高我们将患有ASD的幼儿分层为有意义的 分组。这些知识将有助于开发有效的和生物学上知情的方法， 检测和治疗，这可以减轻并发ADHD和焦虑的长期负面影响， ASD患者的结果。

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.