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

焦虑和抑郁给公共卫生带来了巨大的负担，而且往往在压力时期出现。 然而，对潜在的机制仍然知之甚少，阻碍了改进治疗方法的发展。 虽然内化疾病的病因无疑是复杂和多因素的，但新出现的证据促使 最重要的假设是，威胁和安全的异常神经处理独立地增加了 内在疾病的风险。这项工作表明：（a）对不确定威胁预期的高反应性 增加风险，（B）安全信号不足增加风险，（c）这些关联被放大 消极生活事件（NLE）。来自马里兰州iRisk研究的存档数据提供了一个最佳的 为严格解决这些根本性差距提供平台。iRisk是一个最近完成的前瞻性纵向 一项研究侧重于一个种族多样、性别平衡的新兴成年人样本，这些样本在风险内化方面有所丰富。在 招募，fMRI和一个完善的威胁预期任务被用来量化对不确定性的反应 和某些冲击威胁，以及安全。对大众情绪感知的反应（“威胁相关”的面孔） 任务也进行了评估。智能手机生态瞬时评估（EMA）被用来集中调查 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 动态和第一次有机会评估威胁和安全大脑回路的现实意义。在 同时评估每一波、情绪、症状、功能和社会支持。诊断，尺寸 症状和NLE在0、15和30个月时使用金标准访谈进行评估。这些数据将 使我能够（1）理解威胁和安全循环与内部化出现的相关性 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- 促进日常生活中的情感和行为，（3）探索一个真正的相对预测价值 令人沮丧的威胁预期任务与广泛使用的威胁感知（情绪面孔）任务。冲击 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 潜在的变革机会，加深我们对病因学的理解和完善临床科学理论。 它将为人类和动物的机械模型的发展提供信息，并提供定量的 优先考虑新的生物学和心理社会学目标用于治疗开发和再利用的理由， 包括可扩展的移动健康方法。这个项目建立在我强大的计算和神经成像技能的基础上， 我在研究实施实践方面的丰富经验，以及我的初步经验 使用EMA数据。它将提供一个特殊的工具，在国家的最先进的分析培训 方法，EMA数据收集和最佳实践，内化疾病和研究伦理;以及 发展尖端的研究计划，专业技能和出版记录，以蓬勃发展 作为一名独立的临床情感神经学家

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.