Abstract
Recently, sleep has been recognized as a crucial factor for health and longevity. The daily sleep/wake cycle provides the basis of biorhythm, which controls whole-body homeostasis and homeodynamics. Sleep disturbances can contribute to several physical and psychological disorders, including cardiovascular disease, obesity, depression, and cognitive dysfunction. The clinical use of the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine began in the 1970s. Over the years, physicians have used it as a short-acting anesthetic, analgesic, and antidepressant; however, in-depth research has revealed new possible applications for ketamine, such as for treating sleep disturbances and circadian rhythm disorders. The aim of this narrative review is to examine the literature on the mechanistic role of the antidepressant ketamine in affecting sleep disturbance. Additionally, we discuss the pharmacologic and pharmacokinetic mechanisms of ketamine as an antidepressant and the predictive biomarkers for ketamine’s effect on sleep and cognitive function.
Highlights
Sleep is a dynamic state characterized by behavioral, physiological, and electrophysiological changes
Treatments for sleep disorders may improve sleep-related diseases by aligning physical and psychological functions with circadian sleep/wake rhythm. In this narrative review, we examine the literature on the internal relationship between sleep, cognitive function and depression (Table 1), the consequences of sleep disturbances (Table 2) and the effect of ketamine on sleep disturbances (Table 3)
Neurocognitive effect (R,S)-ketamine can selectively block NMDA receptor expressed on GABA inhibitory interneurons, resulting in a decreased activity of GABAergic interneurons, and de-inhibition of pyramidal neurons, which further increases excitatory neurotransmitter glutamate released from the synaptic cleft, activates the AMPAR, and increases the level of BDNF which increase early sleep slow-wave activity during non-rapid eye movement sleep (REM) sleep The level of brain-derived neurotrophic factor depends on the regulation of eukaryotic elongation factor 2
Summary
Sleep is a dynamic state characterized by behavioral, physiological, and electrophysiological changes.
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