Disgust Overgeneralization in Anorexia Nervosa - PROJECT SUMMARY/ABSTRACT Anorexia nervosa (AN) is a serious mental illness associated with severe medical, nutritional, and psychosocial problems. Emerging evidence suggests that some of the most intractable symptoms of AN, pathological food avoidance and extreme caloric restriction, may result, in part, from disgust generalization, which is the the process by which a disgust response to a conditioned stimulus (CS+) generalizes to a perceptually similar, safe stimulus (e.g., generalization stimulus; GS), and related neural activity among frontolimbic circuitry involved in acute threat (e.g., disgust) processing. However, our knowledge of the role of disgust generalization in AN is extremely limited, due to a lack of systematic research on disgust in the eating disorders field and an overall paucity of knowledge regarding mechanisms underlying AN symptom maintenance. Consistent with NIMH priorities, this application aims to precisely characterize neural dysfunction in AN. The central hypothesis of this study is that frontolimbic functioning associated with disgust overgeneralization contributes to AN symptom maintenance (e.g., restrictive eating, food avoidance). To test this hypothesis, this project will use first establish whether altered frontolimbic neural activation and behavioral patterns during a task that assesses food-specific disgust generalization via measures of instrumental avoidance of conditioned (CS+) and generalization (GS) disgust stimuli in a well-powered sample of 95 adults with AN compared to 85 age- matched non-eating-disorder comparison participants (NC) [Aim 1]. This project will also establish whether changes in neural activation during food-specific disgust generalization relate to changes in AN symptom severity [Aim 2], as well as establish the extent to which neural activation during disgust generalization drives longitudinal AN symptom maintenance [Aim 3]. To accomplish these aims, the investigative team will conduct a study involving a cross-sectional 2-group between-subjects design (Study 1a) and a longitudinal, within- subjects, multi-method (task-based MRI, behavioral tasks, clinical and diagnostic self-report and interview assessments, and ecological momentary assessment [EMA]) study design (Study 1b). Study 1a will compare neural activation patterns of disgust generalization between AN and NC participants. Study 1b will examine associations between neural activity during disgust generalization and rigorous, ecologically valid measures of AN symptom severity (food avoidance, measured via test meal intake; restrictive eating, measured via EMA over time (baseline, 6-month follow-up, 12-month follow-up), and will evaluate a novel mediation model in which disgust generalization drives AN symptom maintenance, via changes in frontolimbic activation over time. Ultimately, this R01 application supports our long-term, overarching goal of identifying neurobiological processes that maintain restrictive eating pathology - information that could be used to develop neurobiologically informed, targeted treatments for AN and other eating disorders.
