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

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2024 · $786,003

## Abstract

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.

## Key facts

- **NIH application ID:** 10883752
- **Project number:** 5R01MH133842-02
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Jonathan P Stange
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $786,003
- **Award type:** 5
- **Project period:** 2023-07-06 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10883752

## Citation

> US National Institutes of Health, RePORTER application 10883752, Ambulatory phenotyping with real-time indices of discordant affect regulation: Exploring opportunities for targeted intervention in depression (5R01MH133842-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10883752. Licensed CC0.

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