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The Orexin/Hypocretin system and its role in the etiology of psychiatric deficits following Traumatic Brain Injury

Year: 2025
Type: article
Abstract: Traumatic brain injury can cause long-term cognitive impairments and psychological symptoms such as anxiety, depression, as well as sleep disturbances. The orexin/ hypocretin system, which controls feeding, sleep, mood, and reward functions, is affected as a result of TBI. This disruption can decrease the density of orexin neurons and dysregulate orexin receptor expression. Abnormal orexin levels and receptor expression may lead to psychiatric symptoms commonly experienced after TBI, such as sleep disorders including insomnia or excessive daytime sleepiness, and mood disorders such as major depressive disorder or anxiety. By understanding how TBI changes the orexin system, we may understand the connection between brain injury and the onset of sleep disorders, depression, and anxiety. Therapeutic strategies targeting the orexin system show promise for mitigating post-TBI psychiatric symptoms. Current treatments, such as orexin receptor antagonists, are being tested for their effectiveness in addressing sleep disorders after TBI. However, research is needed to progress our current understanding to develop targeted treatments that could improve outcomes for TBI patients. It may be advantageous to construct an algorithm that provides information on gender, along with biomarkers for the HPA axis (ACTH, cortisol, DHEA-S), inflammation and autoimmune disease (interleukins, ESR, CRP), blood glucose (diabetes), and genetic variant determination of ADH1B and ALDH2 (susceptibility to alcohol abuse) in order to determine how aggressive the post TBI orexin modulating therapy needs to be for that patient to achieve a favorable outcome. Such clinical algorithms, meta-analyses and more empirical studies are needed to progress our current understanding to develop patient-specific targeted treatments that could improve outcomes for TBI patients.
DOI: 10.64336/001c.131870
Author: Nina Papamichail
Language: English
Open Access status: hybrid
OpenAlex ID: W6902658874
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