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Biol Psychiatry. 2003 Jul 15;54(2):87-95.

The hypocretin/orexin system in health and disease.

Author information

  • 1Center for Narcolepsy, Stanford University, School of Medicine, Psychiatry and Behavioral Sciences, Palo Alto, California 94304, USA.

Erratum in

  • Biol Psychiatry. 2003 Jul 15;54(2):175.


Using positional cloning in a canine model of narcolepsy and mouse gene knockouts, genes involved in the pathogenesis of narcolepsy in animals have been identified. Hypocretin/orexin ligand and hypocretin/orexin receptor genes are key to the pathogenesis of narcolepsy in animals. Mutations in hypocretin-related genes are rare in humans, but hypocretin-ligand deficiency is found in many cases. Hypocretins/orexins are novel hypothalamic neuropeptides involved in various hypothalamic mechanisms, such as energy homeostasis and neuroendocrine function. Hypocretin-deficient human narcolepsy appears to be a more complex condition than a simple sleep disorder, and it may serve as an important disease model for studying hypothalamic function in health and disease.

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