Changes of hypocretin (orexin) system in schizophrenia: from plasma to brain

Lu, J.; Huang, M.L.; Li, J.H.; Jin, K.Y.; Li, H.M.; Mou, T.T.; ... ; Bao, A.M. (2021)

Article / Letter to editor

Hypocretin (also called orexin) regulates various functions, such as sleep-wake rhythms, attention, cognition, and energy balance, which show significant changes in schizophrenia (SCZ). We aimed to identify alterations in the hypocretin system in SCZ patients. We measured plasma hypocretin-1 levels in SCZ patients and healthy controls and found significantly decreased plasma hypocretin-1 levels in SCZ patients, which was mainly due to a significant decrease in female SCZ patients compared with female controls. In addition, we measured postmortem hypothalamic hypocretin-1 -immunoreactivity (ir), ventricular cerebrospinal fluid (CSF) hypocretin-1 levels, and hypocretin receptor (Hcrt-R) mRNA expression in the superior frontal gyms (SFG) in SCZ patients and controls We observed a significant decrease in the amount of hypothalamic hypocretin-1 ir in SCZ patients, which was due to decreased amounts in female but not male patients. Moreover, Hcrt-R2 mRNA in the SFG was decreased in female SCZ patients compared with female controls, while male SCZ patients showed a trend of increased Hat-R1 mRNA and Hcrt-R2 mRNA expression compared with male controls. We conclude that central hypocretin neurotransmission is decreased in SCZ patients, especially female patients, and this is reflected in the plasma.

• schizophrenia
• hypocretin
• orexin, hypocretin receptor
• cerebrospinal fluid
• hypothalamus
• superior frontal gyrus
• plasma

• All authors: Lu, J.; Huang, M.L.; Li, J.H.; Jin, K.Y.; Li, H.M.; Mou, T.T.; Fronczek, R.; Duan, J.F.; Xu, W.J.; Swaab, D.; Bao, A.M.
• Date: 2021-09-01
• Journal: Schizophrenia Bulletin
• Volume: 47
• Issue: 5
• Pages: 1310 - 1319
• DOI: doi:10.1093/schbul/sbab042
• Link: https://pure.knaw.nl/ws/files/181206197/Lu2021SchizoBull.pdf