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

项目总结/摘要 焦虑症是最常见的精神疾病，通常对治疗有抵抗力。青春期 是焦虑症发展和恶化的核心风险期，通常具有慢性病程， 对学业、社会和适应功能产生负面影响，并增加患精神疾病的风险 直到成年研究强调了一些可能导致发展的风险因素 和焦虑的维持。然而，对焦虑的最早前兆或 多种风险因素如何在发展过程中相互作用，从而影响焦虑风险。前瞻性研究 从婴儿期开始，需要解释焦虑的起源，以便（a）可以发现生物标志物 在出现症状之前识别高危青少年，以及（B）可以制定预防策略 并与有风险的人一起实施。本项目的总体目标是测试以下因素的综合影响： 神经，生理，行为和环境的危险因素对焦虑从婴儿期到青春期。 研究目的将通过遵循我们建立的纵向队列（R 01 MH 078829; N=807）来实现， 他们提供了丰富的数据集，包括神经生理学（EEG，ERP）的重复评估， 生理应激反应性、威胁反应性的行为指标，以及环境风险（例如，产妇 精神病理学、负面生活事件、COVID-19相关压力源）。在 根据目前的建议，我们寻求资金支持对13岁儿童进行后续研究。我们将对我们的队列进行表型分析， 焦虑的诊断和诊断，在多种表型，并实施一系列基于大脑的 测量、生理和行为方案以及环境暴露评估，包括 与青少年特别相关的暴露以及与COVID-19疫情相关的暴露。我们将 应用已建立的和新的分析方法的组合来开发诊断神经生物标志物， 青少年的焦虑;确定影响焦虑的积极和消极环境特征- 青春期的相关神经信号，影响从婴儿到 青春期，并缓和神经反应对焦虑风险的影响;确定COVID-19 相关的压力源与儿童期大流行前的特征（神经和行为威胁反应， 生理应激反应性）以影响青少年焦虑风险;以及开发测定谱，包括 从婴儿期到青春期的神经、生理、行为和/或环境特征， 可以很好地预测整个发展过程中的焦虑轨迹我们希望这些研究结果将（a）改善我们的 了解年轻人焦虑风险背后的神经回路，（B）有助于发现鲁棒的 发展知情的多模式配置文件，可以识别处于危险之中的儿童，（c）通知设计 创新的战略，以防止出现的焦虑和更准确地治疗症状的青年， 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.