Janet M. Mullington^a, Tony J. Cunningham^{b, c}, Monika Haack^a, Huan Yang^a

^a Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA; 
^b Department of Psychiatry, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA; 
^c Department of Psychology and Neuroscience, Boston College, Boston, MA, USA

© 2021 The Author(s)
Published by S. Karger AG, Basel

• Chapter 11 graphical abstract

Sleep is one of the pillars of health. Experimental models of acute sleep loss, of chronic partial sleep deprivation, and of sleep fragmentation in healthy sleepers are helpful models of sleep deficiency produced by insufficient sleep duration, sleep timing, and sleep disorders. Sleep deficiency is associated with changes in markers associated with risk for disease. These include metabolic, inflammatory, and autonomic markers of risk. In addition, sleep disruption and sleep deficits lead to mood instability, lack of positive outlook, and impaired neurobehavioral functioning. On a population level, insufficient sleep is associated with increased risk for hypertension and diabetes. Sleep disturbance is very common, and about half the population will report that they have experienced insomnia at some time in their lives. Approximately 10% of the population describe daytime impairment due to sleep disturbance at night, consistent with a diagnosis of insomnia disorder. The hypothalamic neuropeptides, orexin-A and orexin-B, act through G-protein-coupled receptors (orexin-1 and orexin-2 receptors). Dual and selective orexin-2 receptor antagonists have shown efficacy in inducing sleep in men and women with insomnia disorder by accelerating sleep onset and improving sleep efficiency and total sleep time. Further study comparing these medications, in short- and longer-term use models, is recommended. Greater understanding of comparative effects on mood, neurobehavioral, and physiological systems will help determine the extent of clinical utility of dual versus selective orexin receptor antagonists.

• Sleep deficiency leads to impairment in daytime neurobehavioral functioning.
• Reduction of sleep duration by 50% even for a couple of days has negative effects on mood and sociability.
• Sleep deficiency increases markers of risk for metabolic and cardiovascular disease.
• Sleep deficiency impairs central pain-modulatory functions, which are involved in the pathopysiology of chronic pain.

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