Oxytocin system integrates appetite, reward, and stress, offering a therapeutic axis for eating disorders

Feeding and eating disorders are complex conditions where biological survival drives conflict with altered motivation, affect, and reward. Current therapeutic options are limited despite advances in neurobiological and metabolic understanding. The oxytocinergic network has emerged as a promising target due to its dual capacity to regulate energy balance and socio-emotional processing, bridging the gap between metabolic and psychological aspects of these challenging conditions. This review explores its potential as a unifying therapeutic axis.

This systematic review integrated preclinical and clinical evidence to position the oxytocinergic system as a unifying tunable axis across feeding and eating disorders. Researchers synthesized findings from animal models of restrictive feeding, binge-like behavior, and activity-based anorexia. This was combined with translational and clinical evidence in anorexia nervosa, binge eating disorder, and obesity. The review critically assessed the system's role as a pivotal interface linking appetite regulation, reward circuitry, stress responsivity, and social cognition to identify novel therapeutic opportunities.

The review found that oxytocinergic alterations are significantly shaped by the specific phenotype, nutritional status, illness chronicity, and oxytocin receptor genetic/epigenetic variability across clinical populations. A partial dissociation between peripheral and central oxytocin effects was observed. Convergent animal and translational studies consistently position oxytocin as a circuit-level modulator of feeding-reward-stress integration, highlighting its role in complex behavioral regulation. This integration provides a cohesive framework bridging metabolic and affective dimensions of these conditions. However, current intranasal approaches for oxytocin delivery yield modest and domain-specific clinical effects, suggesting a need for more targeted strategies. The conceptualization of the oxytocinergic system as an integrator of metabolic and affective signaling strengthens its positioning as a pharmacological target. This supports the development of precision-guided oxytocinergic interventions.

The oxytocinergic system acts as a pivotal interface linking appetite regulation, reward circuitry, stress responsivity, and social cognition, offering a unifying therapeutic axis.