Ambulatory phenotyping with real-time indices of discordant affect regulation: Exploring opportunities for targeted intervention in depression

项目总结/摘要 情感和生理调节不成功（RAP）是许多精神病理学形式的核心，包括 抑郁症是全球残疾的主要原因之一。重度抑郁症的一个核心特征是 持续的悲伤，这通常是由于难以成功地调节情感和生理。 抑郁症患者在疾病过程中的异质性和对治疗的反应可能是由于存在 多种表型通过不同的机制带来风险。缓解型抑郁症（RMDD） 在日常生活中，在两个不同的调节维度上， 成功--显性调节在改善情感方面的成功程度;生理成功-- 调节尝试后的副交感神经增强，主要是内隐调节过程。 将个体分类为子组（即，表型）根据每个调节维度上的得分， 具有临床实用性，为基于显性和/或隐性的补救提供不同的基于机制的目标， 调控我们的方法包括三个阶段：首先，我们计划通过以下方式表征调控表型： 根据我们先前的研究，筛选rMDD（n=184）和健康对照（n=68）的年轻成人， 在日常生活中成功进行RAP的三维动态评估。第二，参与者将完成 在实验室中进行深入的表型分析，以验证其表型RAP的神经和生理机制 分类.第三，我们将研究心率变异性（HRV）生物反馈对 日常生活中RAP成功的近端指标，特别是对于那些表现出不成功的亚组 RAP。通过基于RAP的生态有效性措施识别和阐明表型机制， 这项研究将有助于解析抑郁症中存在的异质性。确定HRV如何 生物反馈影响特定表型的日常调节成功可以作为迈向 引导精准医疗因此，该项目高度响应NIMH的战略计划，以确定何时， 如何以及为谁进行干预。

PROJECT SUMMARY / ABSTRACT Unsuccessful regulation of affect and physiology (RAP) is central to many forms of psychopathology, including depression, one of the leading causes of disability worldwide. A core feature of major depressive disorder is persistent sadness, which often results from difficulty successfully regulating affect and physiology. Heterogeneity in the course of illness and response to treatment in depression is likely due to the presence of multiple phenotypes that confer risk via distinct mechanisms. Individuals with remitted depression (rMDD) appear to be less successful than controls on two distinct dimensions of regulation in everyday life: Perceived success – how successful explicit regulation is at improving affect; and Physiological success – the degree of parasympathetic augmentation following regulation attempts, primarily an implicit regulation process. Classifying individuals into subgroups (i.e., phenotypes) according to scores on each regulatory dimension can have clinical utility, providing distinct mechanism-based targets for remediation based on explicit and/or implicit regulation. Our approach involves three phases: First, we plan to characterize regulation phenotypes by screening young adults with rMDD (n=184) and healthy comparisons (n=68) based on our previously successful dimensional ambulatory assessment of RAP in everyday life. Second, participants will complete deep phenotyping in the lab to validate neural and physiological mechanisms underlying their phenotypic RAP classification. Third, we will examine the remediating effects of heart rate variability (HRV) biofeedback on proximal measures of RAP success in everyday life, particularly for subgroups who demonstrated unsuccessful RAP. By identifying and elucidating mechanisms of phenotypes based on ecologically-valid measures of RAP success, this study will help to parse the heterogeneity that exists within depression. Determining how HRV biofeedback impacts everyday regulation success for specific phenotypes can serve as an initial step toward guiding precision medicine. Thus, this project is highly responsive to NIMH’s strategic plan to identify when, how, and for whom to intervene.