PROJECT SUMMARY/ABSTRACT Functional dyspepsia (FD) is a chronic gastrointestinal functional/motility disorder that affects up to 12% of US adults with significant morbidity and healthcare costs and has limited treatment options. Detrimental eating- related medical consequences are frequent in FD, with a level of food avoidance/restriction meeting criteria for avoidant/restrictive food intake disorder (ARFID) in up to 40% of adults with FD. However, the biological mechanisms of problematic avoidant/restrictive eating in FD have been underexplored and could inform behavioral and biological intervention targets. This 5-year K23-Patient-Oriented Research Career Development award addresses this research gap by using an innovative, multi-disciplinary approach to examine: (1) differences in gastric sensorimotor functions and satiety hormones among adults with FD and ARFID, FD without ARFID, and healthy controls; and (2) pilot feasibility, preliminary efficacy, and preliminary mechanisms of an exposure-based cognitive-behavioral treatment in patients with FD and ARFID. This project represents the first exploration of the mechanistic role of problematic avoidant/restrictive eating in FD and the potential benefit of an intervention that exposes patients with FD to increased food volume/variety. The training plan corresponding to this project will support Dr. Helen Burton Murray in becoming an independent clinical scientist with a program of research examining biopsychosocial target mechanisms of gastrointestinal functional/motility disorders to inform behavioral and biological treatment interventions. The study aims complement Dr. Burton Murray’s objectives for her advancement as an independent clinical and translational investigator, achieved through four training areas: gastric sensorimotor functions, endocrine regulation of appetite, behavioral clinical trials evaluation and treatment mechanisms, and career development. Training goals will be implemented under the guidance of Dr. Braden Kuo (primary mentor); Drs. Elizabeth A. Lawson and Jennifer J. Thomas (co- mentors); Drs. Brjánn Ljótsson and Brian Healy (consultants); and Drs. Lukas Van Oudenhove, Johnathan Williams, and Laurie Keefer (scientific advisory committee).

PROJECT NARRATIVE Functional dyspepsia (FD) is a chronic gastrointestinal functional/motility disorder which frequently poses detrimental and problematic eating-related medical consequences (e.g., significant weight loss, malnutrition) with avoidant/restrictive food intake disorder (ARFID) present in up to 40% of adults with FD. While treatment options for FD are limited, presence of problematic avoidant/restrictive food intake has not yet been explored to inform treatment approaches and our team’s uncontrolled pilot data suggest that an exposure-based cognitive-behavioral treatment can improve FD outcomes. The proposed multi-disciplinary study aims to determine the role of problematic avoidant/restrictive food intake by (1) comparing gastric sensorimotor functions and satiety hormones among adults with FD and ARFID, FD without ARFID, and healthy controls, and (2) testing the proof-of-concept of an exposure-based cognitive-behavioral treatment in a pilot randomized controlled trial.