Elucidating Causal Mechanisms of Toxic Stress and Links to Psychopathology: An Intensive Longitudinal Study

/Abstract The accumulation of toxic responses to stressors – allostatic load – is strongly associated with a wide array of psychopathological outcomes. Treating or preventing allostatic load stands to improve the well-being and functioning of individuals currently struggling or at risk for psychopathology. Despite this broad consensus, no allostatic load intervention exists. One major limiting factor has been the field’s emphasis on cross-sectional designs which tell who might be at risk but not how and when individuals are at risk. Answers to how and when lay the foundation for treatment development and can be studied using intensive longitudinal designs (ILD). Recently, researchers have leveraged ILD to investigate allostatic load through three dimensions of the stress response: quantity of daily stressors, physiological reactivity, and the subjective psychological response to stressors—perceived stress. Yet, no current research has unpacked the dynamic interactions between all dimensions of the stress response together. This project will fill this significant knowledge gap by leveraging ILD to 1) identify causal links between daily stressors, physiological reactivity, and perceived stress on a day- by-day basis, and 2) use these dynamic processes to improve prediction of short-term psychopathology beyond prior symptom levels. Emerging adulthood is a critical period of elevated stressors and psychological and physiological response to stressors and marks the incidence of multiple forms of psychopathology. Importantly, college students are representative of the emerging adult population and can be easily recruited for participation in research. In this project, 100 college students, and an additional 50 college students, enriched for psychopathological distress, will be recruited from a large public university to take part in a two- week intervention (14 days). On each day, participants will complete two measures of physiological reactivity in the evening (i.e. heart rate variability, pupil light reflex) and three measurements of daily stressors and perceived stress throughout the day (morning, afternoon and evening). Aim 1 will identify to what degree physiological reactivity mediates the effect of daily stressors on perceived stress. Aim 2 will investigate a) whether the combined effects of physiological reactivity and perceived stress predict short-term psychopathology symptoms better than either alone, and, b) whether these variables predict psychopathology symptoms beyond prior symptom levels. Across all aims, we will identify distinct within- and between- person mechanisms to answer the question: what matters and for whom? By elucidating these complex stress dynamics, we will contribute a novel conceptualization and understanding of toxic stress accumulation and set the foundation for future research on intervention and treatments. Project Number: 1F31MH140508-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Mental Health (NIMH) | Principal Investigator: Christophe Delay | Institution: MICHIGAN STATE UNIVERSITY, EAST LANSING, MI | Award Amount: $41,425 | Activity Code: F31 | Study Section: Special Emphasis Panel[ZRG1 F02A-D (20)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11389052