Orexin/hypocretin and major psychiatric disorders

Orexin A and B, also known as hypocretin 1 and 2, are excitory neuropeptides synthesized in the perifornical and lateral hypothalamic areas. Following their discovery in 1998, orexins are now known to be involved in feeding, sleep, stress response, and reward processing. Most importantly, orexin deficiency has been linked to narcolepsy, a neurological sleep-wake disorder. Patients with narcolepsy also present overlapping symptoms with psychiatric disorders, such as anxiety and depressed mood, and even hallucinations, which often lead to misdiagnosis in the initial assessment. In this article, we aim to review studies of the orexin system associated with the three major psychiatric disorders: schizophrenia, major depressive disorder (MDD), and bipolar disorder. In addition to animal and clinical reports, studies of the orexin system in treatment, symptoms and side effects would also be reviewed. Thus far, relatively robust evidence suggests a connection of the orexin system with MDD. Findings of orexin involvement in schizophrenia are inconsistent and only studies in bipolar disorder are limited. While the orexin system might not be firmly associated with diagnosis, it may be useful to target specific symptom within the diagnosis or treatment, such as insomnia, weight gain and polydipsia.