Orexin and circadian influences in sleep and psychiatric disorders: A review of experimental and computational modelling studies

Alok Joshi, Mino D.C. Belle, Kong Fatt Wong-Lin, Hugh D. Piggins

Research output: Chapter or section in a book/report/conference proceedingChapter or section

3 Citations (SciVal)


Psychiatric disorders such as unipolar depression have complex pathologies, which include disruptions in circadian and sleep-wake cycles. At the neurochemical level, psychiatric diseases can also be accompanied by changes in neuromodulator systems such as orexin/hypocretin and the monoamines. Indeed, for decades the monoamine hypothesis of depression has been instrumental in driving discoveries and developments of antidepressant drugs. Recent preclinical and clinical advancement strongly suggests that neuropeptides such as orexin can play an important part in the pathophysiology of depression. Due to the complexity and extensive connectedness of neurobiological systems, understanding the biological causes and mechanisms of psychiatric disorders present major research challenges. In this chapter, we review experimental and computational studies investigating the complex relationship between orexinergic, monoaminergic, circadian oscillators, and sleep-wake neural circuitry. Our main aim is to understand how these physiological systems interact and how alteration in any of these factors can contribute to the behaviours commonly observed in depressive patients. Further, we examine how modelling across different levels of neurobiological organization enables insight into these interactions. We propose that a multiscale systems approach is necessary to understand the complex neurobiological systems whose dysfunctions are the underlying causes of psychiatric disorders. Such an approach could illuminate future treatments.

Original languageEnglish
Title of host publicationOrexin and Sleep
Subtitle of host publicationMolecular, Functional and Clinical Aspects
EditorsT. Sakurai, S. Pandi-Perumal, J. Monti
Place of PublicationCham, Switzerland
PublisherSpringer International Publishing
Number of pages24
ISBN (Electronic)9783319230788
ISBN (Print)9783319230771
Publication statusPublished - 22 Sept 2015


  • Circadian rhythms
  • Computational models
  • Monoamines
  • Neuromodulators
  • Orexin (hypocretin)
  • Psychiatric disorders
  • Sleep

ASJC Scopus subject areas

  • Medicine(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)


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