Neural, Physiological, Behavioral, and Environmental Risk Markers of Anxiety from Infancy to Adolescence

项目摘要/摘要 焦虑症是最常见的精神疾病，往往对治疗产生抵触。青春期 是发展和加剧焦虑的核心风险期，焦虑通常有一个慢性病程， 对学习、社交和适应能力产生负面影响，增加患精神疾病的风险 一直到成年。研究强调了一些可能导致这种发展的风险因素。 以及保持焦虑。然而，人们对焦虑或焦虑的最早先兆的了解有限 多种风险因素在发育过程中和发展过程中如何相互作用，从而影响焦虑风险。前瞻性研究 需要从婴儿期开始解释焦虑的起源，以便(A)发现生物标记物 在出现症状之前识别高危青年和(B)可以制定预防战略 并与那些处于危险中的人一起实施。当前项目的总体目标是测试以下各项的综合效果 神经、生理、行为和环境风险因素对从婴儿期到青春期的焦虑。 研究目标将通过遵循我们建立的纵向队列(R01 MH078829；N=807)来实现， 提供了丰富的数据集，包括对神经生理学(脑电、事件相关电位)的重复评估， 生理应激反应、威胁反应的行为指标和环境风险(例如，母亲 精神病理学、负性生活事件、新冠肺炎相关压力源)。在 根据目前的提案，我们寻求资金支持13岁以下的后续研究。我们将对我们的队列进行表型分析 焦虑症状和诊断，跨越多种表型，并实施一系列基于大脑的 环境暴露的测量、生理和行为方案以及评估，包括 与青春期特别相关的暴露和与新冠肺炎大流行有关的暴露。我们会 应用已建立的和新的分析方法相结合的方法来开发诊断神经生物标记物 青春期的焦虑；识别影响焦虑的积极和消极的环境特征- 青春期的相关神经信号，影响从婴儿期到 青春期，以及缓和神经反应性对焦虑风险的影响；决定新冠肺炎如何 相关应激源与儿童大流行前的特征(神经和行为威胁反应性， 生理应激反应)，以影响青少年焦虑风险；并开发包括 从婴儿期到青春期的神经、生理、行为和/或环境特征 有力地预测焦虑在整个发育过程中的轨迹。我们预计调查结果将(A)改善我们的 了解青少年焦虑风险背后的神经回路，(B)有助于发现强健的 可识别高危儿童的发育知情多模式简档，以及(C)为设计 预防焦虑的出现和更准确地治疗有症状的青年的创新战略 解决和纠正非典型神经过程及其下游行为表现。

PROJECT SUMMARY/ABSTRACT Anxiety disorders are the most common psychiatric illnesses and are often resistant to treatment. Adolescence is a core risk period for the development and exacerbation of anxiety, which often has a chronic course, negatively affecting academic, social, and adaptive functioning, and increasing the risk for mental illness through adulthood. Research has highlighted a number of risk factors that likely contribute to the development and maintenance of anxiety. However, there is limited understanding of the earliest precursors of anxiety or how multiple risk factors interact within and across development to influence anxiety risk. Prospective studies beginning in infancy are needed to explicate the origins of anxiety so that (a) biomarkers can be discovered that identify at-risk youth prior to the emergence of symptoms and (b) preventive strategies can be developed and implemented with those at risk. The overall goal of the current project is to test the combined effects of neural, physiological, behavioral, and environmental risk factors on anxiety from infancy through adolescence. The study aims will be accomplished by following our established longitudinal cohort (R01 MH078829; N=807), who have provided a rich dataset, including repeated assessments of neurophysiology (EEG, ERP), physiological stress reactivity, behavioral indicators of threat reactivity, and environmental risk (e.g., maternal psychopathology, negative life events, COVID-19 related stressors) between infancy and age 7 years. In the current proposal, we seek funds to support a follow-up study to age 13 years. We will phenotype our cohort for anxiety symptomatology and diagnoses, across multiple phenotypes, and implement a battery of brain-based measures, physiological and behavioral protocols, and assessments of environmental exposures, including exposures of particular relevance in adolescence and exposures related to the COVID-19 pandemic. We will apply a combination of established and novel analysis approaches to develop diagnostic neural biomarkers of anxiety in adolescence; identify positive and negative environmental characteristics that influence anxiety- relevant neural signatures in adolescence, that affect anxiety-related neural trajectories from infancy to adolescence, and that moderate the effects of neural reactivity on anxiety risk; determine how COVID-19 related stressors interact with childhood pre-pandemic characteristics (neural and behavioral threat reactivity, physiological stress reactivity) to influence adolescent anxiety risk; and to develop assay profiles comprising neural, physiological, behavioral, and/or environmental characteristics from infancy through adolescence that robustly predict anxiety trajectories across development. We expect that the findings will (a) improve our understanding of the neural circuitry underlying anxiety risk in youth, (b) contribute to the discovery of robust developmentally-informed multi-modal profiles that can identify at-risk children, and (c) inform the design of innovative strategies to prevent the emergence of anxiety and to treat more precisely symptomatic youth by addressing and correcting atypical neural processes and their downstream behavioral manifestations.