Fig. 1. Binge-induced plasticity of orexin neurons contributes to the pathophysiology of BED.

We propose that binge eating results in orexin system plasticity similar to that induced by drugs of abuse, including increased hypothalamic orexin cell numbers, greater orexin input to reward and arousal centers, and greater reactivity to food-related stimuli. This general enhancement of orexin function is associated with the development of a hypermotivated state for food, which in turn increases proclivity to binge eat. Additionally, inappropriately high orexin system function results in hyperarousal and sleep dysregulation, which in turn promotes an increased risk of binge eating due to weakened inhibitory control, as a strategy to combat drowsiness during the daytime, and/or behavioral entrainment. Combined, this creates a self-promoting loop that serves to exacerbate the pathophysiology of BED. Thus, strategies that dampen orexin system signaling, such as orexin receptor antagonists, might be effective at breaking this loop and treating both dysregulated eating and sleep in BED.