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

项目摘要/摘要 情感和生理调节不成功(RAP)是许多形式的精神病理学的核心，包括 抑郁症是全世界导致残疾的主要原因之一。严重抑郁障碍的一个核心特征是 持续的悲伤，通常是由于难以成功地调节情绪和生理造成的。 抑郁症的病程和治疗反应的异质性可能是由于存在 通过不同的机制赋予风险的多种表型。缓解性抑郁症(RMDD)患者 似乎不如对日常生活中两个截然不同的监管维度的控制成功：感知 成功-显性调控在改善情绪方面的成功程度；以及生理成功-程度 调节尝试后的副交感增强，主要是一个隐含的调节过程。 根据每个监管维度上的分数将个体分类为亚组(即，表型)可以 具有临床实用性，根据显式和/或隐式提供不同的基于机制的补救目标 监管。我们的方法包括三个阶段：第一，我们计划通过以下方式来表征调控表型 根据我们以前的研究，筛查患有rMDD的年轻人(n=184)和健康对照(n=68) RAP在日常生活中的成功维度动态评估。第二，参与者将完成 在实验室中进行深入的表型鉴定，以验证其表型说唱的神经和生理机制 分类。第三，我们将研究心率变异性(HRV)生物反馈对 日常生活中说唱成功的近距离测量，特别是对那些表现不成功的小组 说唱。通过鉴定和阐明基于生态有效的RAP措施的表型机制 如果成功，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 生物反馈影响日常调控特定表型的成功可以作为迈向 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， 如何干预，以及为谁干预。

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.