Attentional, temperamental, and physiological process underlying anxiety in preschoolers with ASD

项目摘要 焦虑症在儿童时期非常普遍，并且与实质性损害和 残疾。焦虑症状在患有ASD的学龄前儿童中广泛存在，限制了他们的学习和社交 与自闭症核心症状相关的困难之外的互动机会。我们的前期工作 表明焦虑的气质前兆在ASD患者生命的第二年已经升高。 然而，关于ASD中焦虑症状出现的潜在机制的知识仍然存在， 有限公司这个项目将实验量化注意力，情感，行为，生理， 与4岁ASD儿童焦虑相关的气质因素（n=160），其他发育障碍 和关注（ATYP，n=80），和典型的发展（TYP，n=80）。我们会调查 情感注意力偏见威胁（ABT）和情绪调节功能以及 假设，但相对未探索，这些功能在ASD的新兴焦虑中的作用。ABT代表 对威胁的快速注意力反应，表现为需要更长的潜伏期来使注意力与 威胁性的刺激ABT是临床和亚临床的最佳复制的神经行为标志物之一。 焦虑减少这种偏见降低了学龄儿童的焦虑症状，暗示ABT在维持中 焦虑考虑到注意力系统与ASD有关，ABT提供了一个未经探索但高度 创新和生成的框架，调查机制的出现焦虑， 患有ASD的儿童。这份提案中的关键问题是：（1）自闭症儿童是否更有偏见 比其他四岁的孩子更容易受到威胁(2)ABT与4岁儿童焦虑严重程度相关吗 有和没有ASD？(3)ABT的各个方面在2岁以下儿童焦虑症状的出现中起什么作用？ 到4年？(4)考虑到幼儿期焦虑表达的异质性， 基于诊断类别的神经行为和生理测量的亚组， 关于独特的潜在机制和新的治疗目标或策略？为了回答这些问题， 我们将使用眼动追踪注意力来评估与焦虑相关的注意力对威胁的反应 在我们的实验室开发和测试的脱离任务。我们还将研究在体内对威胁的反应， 情感、注意力和生理水平。将这些应对威胁的多模式指数结合起来， 允许以无与伦比的方式量化焦虑相关特征，并评估每个特征的 在焦虑症状首次变得明显时，对临床表型的独特贡献。通过 把我们的调查集中在4岁的孩子身上，我们的目标是从翻译的角度来确定早期的 “发展束缚”使儿童的发展偏向于适应不良的途径。此外，委员会认为， 基于神经认知注意力和生理反应识别亚组可能有助于 发展以神经科学为基础的方法，对学龄前儿童焦虑症进行分类。

Project Summary Anxiety disorders are highly prevalent in childhood and are associated with substantial impairment and disability. Symptoms of anxiety are widespread in preschoolers with ASD, limiting their learning and social interaction opportunities above and beyond difficulties related to core autism symptoms. Our preliminary work suggests that temperamental precursors of anxiety are already elevated in the second year of life in ASD. However, knowledge about the mechanisms underlying the emergence of anxiety symptoms in ASD remains limited. This project will experimentally quantify attentional, affective, behavioral, physiological, and temperamental factors associated with anxiety in 4-year-olds with ASD (n=160), other developmental disorders and concerns (ATYP, n=80), and typical development (TYP, n=80). We will investigate the associations between affective attentional biases to threat (ABT) and emotional-regulatory functions as well as the hypothesized, but relatively unexplored, role of these features in emerging anxiety in ASD. ABT represents a rapid attentional response to threat that is evidenced by longer latencies required to decouple attention from threatening stimuli. ABT is among the best-replicated neurobehavioral markers of clinical and subclinical anxiety. Decreasing this bias lowers anxiety symptoms in school-age children, implicating ABT in maintenance of anxiety. Give that attentional system has been implicated in ASD, ABT offers an unexplored but highly innovative and generative framework for investigating mechanisms underlying the emergence of anxiety in very young children with ASD. The key questions in this proposal are: (1) Are children with ASD more biased toward or away from threat than other 4-year-olds? (2) Is ABT associated with anxiety severity in 4-year-olds with and without ASD? (3) What role do the facets of ABT play in the emergence of anxiety symptoms from 2 to 4 years? (4) Given the heterogeneity of anxiety expression in early childhood, can we identify homogeneous subgroups based on neurobehavioral and physiological measures across diagnostic categories that will inform about unique underlying mechanisms and novel treatment targets or strategies? To answer these questions, we will evaluate anxiety-related aspects of attention in response to threat using an eye-tracking attention disengagement task developed and tested in our lab. We will also examine in vivo reactivity to threat at affective, attentional, and physiological levels. Combining these multimodal indices of response to threat will allow for quantification of anxiety-related features in an unparalleled manner and evaluation of each feature's unique contributions to clinical phenotypes, at the time when anxiety symptoms first become apparent. By focusing our investigation on 4-year-olds we aim to identify, essential from a translational standpoint, the early “developmental tethers” that bias children's development toward maladaptive pathways. Furthermore, identifying subgroups based on neurocognitive attentional and physiological responses may contribute to the development of a neuroscience-based approach to classification of anxiety disorders in preschoolers.