Brain-Gut biomarkers of anxiety and depressive symptoms in youth with inflammatory bowel disease

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Project Summary/Abstract This K23 Career Development Award application is designed to prepare the PI for her long-term career goal of becoming an independent clinical scientist with lines of research focused on the brain-gut axis as it relates to disease, emotional, and behavioral functioning in pediatric patients diagnosed with inflammatory bowel disease (IBD). Consistent with this goal, the proposed research and career development plan will build upon pilot data collected during the applicant's KL2 Award demonstrating a positive and significant relationship between high stress reactivity in response to a standardized laboratory stressor and greater mental health symptoms in youth newly diagnosed with IBD. These preliminary data suggest that stress reactivity (as measured via skin conductance, a reliable indicator of autonomic nervous system (ANS) activity) in response to a stress challenge, may serve as a biomarker of psychosocial functioning that could then be used to risk stratify youth who would benefit from coping skills interventions. Thus, the goals of the current study are to conduct a longitudinal observational study to (1) compare relationships between stress reactivity and mental health symptoms in patients with IBD and healthy controls and (2) examine indices of stress reactivity as novel predictors of mental and physical health outcomes in youth with IBD. To this end, we propose to recruit an observational, longitudinal cohort of youth newly diagnosed with IBD (N=60) to be compared to age and sex-matched healthy controls (N=60) at baseline and then followed at six assessment points across 24-months. Indices of stress processing to be assessed include skin conductance and heart rate variability, both validated psychophysiological measures of stress processing. Further, this project will develop a biofeedback enhanced coping skills training program using a treatment group (n=20) and wait-list control group (n=20) to which patients with IBD who screen positive for symptoms of anxiety and/or depression will be randomized. We will evaluate the treatment's feasibility, acceptability, and preliminary outcomes on psychological symptoms, autonomic reactivity, and IBD symptoms. Career development activities will take place under the mentorship of an interdisciplinary mentoring team to provide advanced training in 1) clinical and translational research, 2) longitudinal data analysis and RCT methodology to support intervention development, 3) brain-gut processes and clinical management relevant to pediatric IBD, and 4) scholarly productivity and grant writing. Findings from this K23 proposal will be instrumental in demonstrating longitudinal trajectories of disease and psychosocial functioning in newly diagnosed youth with IBD and determining whether indices of stress processing can serve as objective biomarkers of risk. Findings will be used to inform refined iterations of our biofeedback enhanced coping skills treatment protocol with focus on determining mechanisms of treatment effect, implementation to minimize burden on families, and a future randomized clinical trial.