CHRONIC SOCIAL STRESS DRIVES DIVERGENT FEEDING PHENOTYPES THROUGH SYNAPTIC PLASTICITY IN HYPOTHALAMIC CIRCUITS

Eating disorder (EDs), such as anorexia nervosa (AN), bulimia nervosa (BN) and binge eating disorder, are among the most prevalent psychiatric disorder. Social stress is a major risk factor for Eds. Individuals often develop distinct and opposite alterations in feeding behavior to react to stress. However, it remains unclear how prolonged social stress sculpts neural circuits and finally elicits divergent EDs. Using a chronic social defeat stress (CSDS) model in mice, we combined automated behavioral monitoring with deep learning–based behavioral analysis to precisely quantify feeding patterns, alongside metabolic and social behavioral assessments. Following CSDS exposure, mice segregated into two distinct feeding phenotypes, characterized by either increased or decreased food intake, indicating robust individual differences in stress-induced eating behavior. To explore the underlying circuit mechanisms, we examined synaptic properties of arcuate nucleus (ARC). Electrophysiological recordings revealed enhanced synaptic strength in both agouti-related peptide (AgRP) neurons and proopiomelanocortin (POMC) neurons following CSDS. Together, these findings demonstrate that chronic social stress induces divergent eating disorder–like phenotypes and is accompanied by synaptic strengthening in feeding-related neuronal populations in ARC. This work provides a circuit-level basis for understanding individual variability in stress-related eating dysregulation and offers insight into how stress-driven synaptic plasticity within hypothalamic circuits may contribute to maladaptive feeding behaviors.