PROJECT SUMMARY/ABSTRACT Avoidant/restrictive food intake disorder (ARFID) is identified as a restrictive eating disorder in DSM-5 and is associated with substantial medical morbidity, psychiatric comorbidity, and high treatment costs. Maintenance mechanisms for ARFID are unknown. However, the cognitive behavioral model of ARFID suggests that negative reinforcement, via reductions in negative affect, may be key in understanding these highly persistent and medically compromising behaviors. This 5-year K23-Patient-Oriented Research Career Development award application addresses this hypothesis using an innovative, multi-disciplinary approach to examine differences in neural circuitry and hormone functioning in adults with ARFID compared to healthy controls (HC) and to explore the relationships between real-time emotions and behaviors with brain responsivity and endocrine signaling to food stimuli. Specifically, this proposal leverages ongoing data collection from a funded R01 (MH108595) investigating the neurobiology of ARFID in youth and extends these methods by focusing on adults and including one week of ecological momentary assessment (EMA). Activation in the amygdala, hippocampus, anterior insula, anterior cingulate cortex, and medial prefrontal cortex (brain regions in the limbic and paralimbic circuits governing emotional processing) as well as cortisol and oxytocin levels around a standardized meal (hormones associated with mood and anxiety) will be compared between adults with ARIFD and HC. EMA ratings of negative emotions and eating behaviors will be used to test whether negative affect is reduced following common problematic eating behaviors (i.e., food refusal) in ARFID. As a final aim, this study will explore if activity in limbic/paralimbic circuitry and aberrant cortisol and oxytocin correlate with negative affect levels as well as reports of avoidant/restrictive eating during the one-week EMA period. This project represents the first exploration of ARFID in adults, the first examination of emotional functioning in ARFID, and a rigorous first test of the cognitive-behavioral model of ARFID. The training plan corresponding to this project will support Dr. Kendra R. Becker in becoming an independent clinical scientist with a program of research examining neurobiological underpinnings of affect and reward maintenance mechanisms in feeding/eating disorders to better understand illness trajectory and inform personalized formulations of pathology. Each aim of the study corresponds to a specific training goal, which will map onto four main areas of competency for Dr. Becker: (1) reproducible fMRI methodology, (2) study design and analysis/interpretation of endocrine data, (3), EMA methodology including advanced longitudinal data analysis integrating neurobiological variables, and (4) career development. Training goals will be implemented under the guidance of Dr. Jennifer J. Thomas (primary mentor), Drs. Elizabeth A. Lawson and Laura M. Holsen (co-mentors), Drs. Stephen A. Wonderlich and Ross D. Crosby (collaborators), and Drs. Kamryn T. Eddy and Madhusmita Misra (other significant contributors).

PROJECT NARRATIVE Avoidant/restrictive food intake disorder (ARFID) is a serious mental and physical health condition which poses major public health problems due to severe impacts on growth, nutritional status, and psychosocial functioning. Although mechanisms that maintain problematic eating behaviors in ARFID are largely unknown, emotion dysregulation is common in eating disorders and our team’s newly developed cognitive-behavioral model of ARFID suggests that avoidant/restrictive eating is negatively reinforced via reductions in negative affect. The proposed multi-disciplinary study aims to determine the role of negative emotions in the maintenance of ARFID symptoms by first comparing activation in brain regions involved in emotion processing and key hormones related to emotional functioning between adults with ARFID and healthy adults, and second integrating real- time reports of negative emotions and avoidant/restrictive eating behaviors with neural circuitry and affect- related hormones to empirically evaluate the cognitive-behavioral model of ARFID.