Using Functional Neuroimaging and Smartphone Digital Phenotyping to Understand the Emergence of Internalizing Illness

焦虑和抑郁给公共健康带来了巨大的负担，并且经常在压力时期出现。 然而，其潜在机制仍知之甚少，这阻碍了改进治疗方法的开发。 虽然内化疾病的病因无疑是复杂且多因素的，但新出现的证据促使人们 总体假设是，威胁和安全的异常神经处理独立地导致增加 内化疾病的风险。这项工作表明：(a) 对不确定威胁预期的过度反应 增加风险，(b) 安全信号不足会增加风险，(c) 这些关联被放大 接触负面生活事件（NLE）。马里兰州 iRisk 研究的档案数据提供了最佳的 严格解决这些基本差距的平台。 iRisk 是最近完成的前瞻性纵向研究 研究重点是种族多样化、性别平衡的新兴成年人样本，这些样本丰富了内化风险。在 使用登记、功能磁共振成像和完善的威胁预期任务来量化对不确定性的反应 和某些冲击威胁以及安全。对流行情绪感知的反应（“与威胁相关的”面孔） 还评估了任务。智能手机生态瞬时评估（EMA）深入探究 0、6、24 和 30 个月的日常体验，提供前所未有的多年情绪评估 动态以及评估威胁和安全大脑电路的现实意义的第一次机会。在 还评估了每个波、情绪、症状、功能和社会支持。诊断，维度 症状和 NLE 在 0、15 和 30 个月时使用黄金标准访谈进行评估。这些数据将 使我能够（1）理解威胁和安全回路与内化的出现的相关性 症状/诊断，（2）了解它们在更接近病因的病理学出现中的作用- 促进日常生活中的感受和行为，以及（3）探索真正的预测的相对预测优点 令人痛苦的威胁预期任务与广泛使用的威胁感知（情绪面孔）任务。影响。 内化疾病是人类痛苦和发病的主要原因。该项目将提供一个 加深我们对病因学的理解和完善临床科学理论的潜在变革机会。 它将为人类和动物机械模型的发展提供信息，并提供定量的 优先考虑新的生物和心理社会目标以进行治疗开发和重新利用的理由， 包括可扩展的移动医疗方法。这个项目建立在我强大的计算和神经影像技能的基础上， 我在研究实施的实际方面的丰富经验以及我的初步经验 使用 EMA 数据。它将为最先进的分析培训提供一个特殊的工具 方法、EMA 数据收集和最佳实践、内化疾病和研究道德；并为 开发繁荣所需的尖端研究计划、专业技能和出版记录 作为一名独立的临床情感神经科学家。

Anxiety and depression impose a staggering burden on public health and often emerge during times of stress. Yet the underlying mechanisms remain poorly understood, thwarting the development of improved treatments. While the etiology of internalizing illness is undoubtedly complex and multifactorial, emerging evidence motivates the overarching hypothesis that aberrant neural processing of Threat and Safety independently confer increased risk for internalizing illnesses. This work suggests that: (a) hyper-reactivity to Uncertain Threat anticipation increases risk, (b) deficient Safety Signaling increases risk, and (c) these associations are magnified by exposure to Negative Life Events (NLEs). Archival data from the Maryland iRisk Study provide an optimal platform for rigorously addressing these fundamental gaps. iRisk is a recently completed prospective-longitudinal study focused on a racially diverse, sex-balanced sample of emerging adults enriched for internalizing risk. At enrollment, fMRI and a well-established Threat-anticipation task were used to quantify reactivity to Uncertain and Certain Shock-Threat, as well as Safety. Reactivity to a popular emotion-perception (‘threat-related’ faces) task was also assessed. Smartphone ecological momentary assessment (EMA) was used to intensively probe daily experience at 0, 6, 24, and 30 months, providing an unprecedented multi-year assessment of mood dynamics and a first opportunity to assess the real-world significance of Threat and Safety brain circuitry. At each wave, mood, symptoms, function, and social support were also assessed. Diagnoses, dimensional symptoms, and NLEs were assessed using gold-standard interviews at 0, 15, and 30 months. These data will enable me to (1) understand the relevance of Threat and Safety circuity to the emergence of internalizing symptoms/diagnoses, (2) understand their role in the emergence of more etiologically proximal pathology- promoting feelings and behaviors in daily life, and (3) explore the relative predictive merits of a genuinely distressing Threat-anticipation task vs. a widely used Threat-perception (emotional-faces) task. Impact. Internalizing illnesses are a leading cause of human misery and morbidity. This project would provide a potentially transformative opportunity to deepen our understanding of etiology and refine clinical science theory. It would inform the development of mechanistic models in humans and animals, and provide a quantitative rationale for prioritizing new biological and psychosocial targets for therapeutics development and repurposing, including scalable mHealth approaches. This project builds on my strong computational and neuroimaging skills, my extensive experience with practical aspects of study implementation, and my preliminary experiences working with EMA data. It would provide an exceptional vehicle for training in state-of-the-art analytic approaches, EMA data collection and best-practices, internalizing illness, and research ethics; and for developing the cutting-edge research program, professional skills, and publication record necessary to flourish as an independent clinical affective neuroscientist.