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.