Autonomic and neural mechanisms of ruminative… (F31MH146547) – Project Grant to University Of Southern…

Abstract: Depression is a leading cause of disability worldwide and is characterized by a high rate of recurrence. Identifying mechanisms that confer vulnerability to recurrence is critical for improving prevention efforts. Ruminative brooding, a passive, self-critical focus on the causes and consequences of negative mood, is a robust cognitive predictor of recurrence. Brooding prolongs distress through a reciprocal cycle with negative affect (NA), such that elevations in NA trigger brooding which, in turn, prolongs and amplifies NA and impairs effective emotion regulation. Thus, delineating the mechanisms that sustain this vicious cycle is essential. Laboratory research suggests that inflexibility in autonomic and neural systems influences the strength of the coupling between NA and brooding, yet IT remains unclear how these processes unfold in real-world contexts. Further, the extent to which distinct directional components of this maladaptive cycle differentially contribute to recurrence risk has not been clearly established. Clarifying when individuals are most vulnerable to brooding and its affective consequences in daily life, why some individuals show tighter coupling between NA and brooding over time, and which direction of this cycle confers the greatest recurrence risk is essential for identifying mechanisms that can be leveraged for prevention. These insights could guide the development of more precise, mechanism-based strategies to reduce brooding and its affective consequences and ultimately prevent depressive recurrence. As such, this work directly supports nimh priorities to identify brain-behavior mechanisms of risk that inform targeted prevention strategies. This project integrates ecological momentary assessment, ambulatory autonomic physiology, and functional magnetic resonance imaging (fmri) from an ongoing NIH-funded study to characterize biobehavioral mechanisms of the NA-brooding cycle in daily life in young adults with remitted depression and never- depressed controls. The project aims to: (1) derive ecologically valid indices capturing distinct components of the NA-brooding cycle; (2) examine how fluctuations in autonomic activity moderate this cycle in daily life; (3) identify task-based and resting-state neural correlates of individual differences in the strength of cycle components; and (4) test whether cycle components prospectively predict depressive recurrence. The fellowship training plan will provide rigorous instruction in intensive longitudinal modeling, task-based fmri analysis, multimodal data integration, and grant writing to support completion of the proposed project and development of essential skills for research independence. Training will occur at the university of southern california under the mentorship of established interdisciplinary experts and will include structured coursework and hands-on experience with a large multimodal dataset. Collectively, these training activities and the proposed research will position the applicant to pursue an independent research career at an R1 institution focused on investigating biobehavioral mechanisms of real-world emotion dysregulation and depression risk.

Autonomic and neural mechanisms of ruminative brooding and its emotional consequences in daily life in remitted depression

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