A 11C-UCB-J PET Study of Synaptic Density in Binge Eating Disorder (BED) - Abstract Binge eating disorder (BED) is a common and debilitating eating disorder [1-6]. An improved understanding of the neurobiology of BED will aid treatment development efforts. Multiple studies on the neurobiology of BED converge on the identification of the prefrontal cortex (PFC)-insular-striatal structures as prime regions and circuits [7-24]. However, there is a significant gap when it comes to understanding neurobiological underpinnings of PFC-insular-striatal alterations at a micro-architectural level (i.e., synaptic plasticity or synaptic density). Notwithstanding current gaps, preclinical and clinical literature suggests there is significant neurobiological overlap between substance use disorders (SUDs) and BED, such as alterations in similar areas [25, 26], similar clinical features (e.g., compulsive food or drug intake) [27-29], and potential common pharmacological interventions (e.g., lisdexamfetamine, topiramate, and phentermine for cocaine use disorder and BED) [30-38]. Preclinical studies show the capacity of certain pharmacological agents, including stimulants, to produce micro- architectural changes in fronto-insular-striatal structures as well as an association between synaptic density/dendritic branching in pyramidal cells of the PFC and working memory, reversal learning, and behavioral flexibility [39-54]. At a clinical level, our group has developed a novel radiotracer, 11C-UCB-J, for imaging synaptic density in the living human brain using positron-emission tomography (PET) [55-58]. Thus, the current exploratory/developmental (PA-21-235) R21 aims to measure for the first time synaptic density in the PFC, insular cortex, and ventral striatum of unmedicated BED subjects (N =18), as compared to Healthy Controls (HCs; N =18), using 11C-UCB-J PET. BED participants will undergo single 11C-UCB-J PET scans as outpatients and HC data will be obtained from previous and ongoing studies. BED participants will also complete cognitive and behavioral assessments based on Research Domain Criteria (RDoC) positive valence and cognitive systems as well as assessments of BED severity and eating questionnaires. We hypothesize that synaptic density will be decreased in four a priori PFC areas (i.e., anterior cingulate cortex, ventromedial PFC, dorsolateral PFC, and lateral orbitofrontal cortex), in the insular cortex, and in the ventral striatum in BED as compared to HC subjects. We also hypothesize no changes in white matter regions such as centrum semiovale. In exploratory aims, we also will explore: 1) correlations between 11C-UCB-J PET outcomes and BED severity as well as measures of behavioral/cognitive functioning, 2) differences in synaptic density between BED and 2a) CUD and 2b) obese (OB) and lean groups from previous and ongoing studies and 3) whole-brain differences between BED and HC groups using general linear model (GLM) and independent component analysis (ICA). If funded, this will be the first translational study examining synaptic density in vivo in adults with BED. Positive results could inform future studies on biomarker’s development as well as studies elucidating mechanisms of action of treatments and longitudinal natures of changes in synaptic density.
