Orexins are highly involved in regulating the circadian rhythm, the brain’s reward mechanism, and the neuroendocrine response to stress. The disruption of orexin regulation is known to be associated with depression. Preclinical studies in rodents have identified the dorsomedial/perifornical and lateral areas of the hypothalamus as the population of orexinergic neurons that are primarily responsible for mediating depression-induced neuroanatomical changes in the brain. There is still no consensus regarding whether hyperactivity or hypoactivity of orexin signaling is responsible for producing depressive-like behaviour. Likewise, clinical studies indicated a general disruption in orexin signaling in depressive patients, but did not report definitive evidence of either hyperactivity or hypoactivity. Nevertheless, given the various reciprocal connections between orexin neurons and multiple brain regions, it is plausible that this involves a differential signaling network with orexin neurons as the coordination center. Here, an overview of preclinical and clinical evidence is provided as a basis for understanding the consequences of altered orexin signaling on neural circuitries modulating different aspects of the physiopathology of depression.

食欲素高度参与调节昼夜节律，大脑的奖赏机制以及对压力的神经内分泌反应。已知食欲肽调节的破坏与抑郁症有关。在啮齿动物中的临床前研究已确定下丘脑的背侧/周围神经和外侧区域为主要负责介导抑郁症诱发的大脑神经解剖变化的食欲能神经元。关于食欲肽信号转导过高或过低是否会导致产生抑郁样行为尚无共识。同样，临床研究表明，抑郁症患者的食欲素信号传导普遍中断，但没有报告过度活跃或过度活跃的确切证据。不过，考虑到orexin神经元和多个大脑区域之间的各种相互联系，这可能涉及以orexin神经元为协调中心的差分信号网络。在这里，提供了临床前和临床证据的概述，作为了解改变orexin信号传导对调节抑郁症生理病理学不同方面的神经回路的后果的基础。