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

项目摘要 焦虑症在儿童中非常普遍，并与实质性的损害和 残疾。焦虑症状在患有自闭症的学龄前儿童中很普遍，限制了他们的学习和社交 超越与核心自闭症症状相关的困难的互动机会。我们的前期工作 这表明焦虑的气质先兆在ASD的第二年就已经升高了。 然而，关于ASD出现焦虑症状的潜在机制的知识仍然存在 有限的。这个项目将在实验上量化注意力、情感、行为、生理和 与患有自闭症(n=160)和其他发育障碍的4岁儿童焦虑相关的气质因素 关注(ATYP，n=80)和典型发展(TYP，n=80)。我们将调查这些联系 情感注意对威胁的偏向(ABT)与情绪调节功能之间的关系 这些特征在ASD新出现的焦虑中的作用是假设的，但相对未被探索。ABT代表一种 对威胁的快速注意力响应，表现为需要更长的延迟来将注意力与 威胁性刺激。ABT是临床和亚临床中复制最好的神经行为标记物之一 焦虑。减少这种偏见可以降低学龄儿童的焦虑症状，这意味着ABT与维持性疾病有关 焦虑。鉴于注意力系统与ASD有牵连，ABT提供了一种未被探索但高度 研究焦虑出现的潜在机制的创新和生成性框架 患有自闭症的非常小的儿童。这项提案的关键问题是：(1)患有自闭症的儿童是否更有偏见 比其他4岁儿童更倾向于威胁还是远离威胁？(2)ABT与4岁儿童的焦虑程度相关吗？ 有无ASD？(3)ABT的各方面在出现焦虑症状中起什么作用？ 到4岁？(4)考虑到儿童早期焦虑表达的异质性，我们能识别同质性吗？ 基于跨诊断类别的神经行为和生理测量的子组，将向 关于独特的潜在机制和新的治疗目标或策略？要回答这些问题， 我们将使用眼球跟踪注意力来评估与焦虑相关的注意力方面，以应对威胁 在我们的实验室开发并测试了脱离任务。我们还将检查体内对威胁的反应性 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在一起将 允许以无与伦比的方式量化与焦虑相关的特征，并评估每个特征 在焦虑症状第一次显现时，对临床表型的独特贡献。通过 将我们的调查集中在4岁的儿童身上，从翻译的角度来看，我们的目标是确定早期 “发育系绳”，使儿童的发展偏向不适应的路径。此外， 根据神经认知、注意力和生理反应识别亚群可能有助于 以神经科学为基础的学龄前儿童焦虑症分类方法的发展。

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.