Melatonin, Circadian Dysregulation, and Sleep in Mental Disorders

Sleep is a behavioral process that is governed by both homeostatic and circadian processes. While the intensity and duration of sleep is governed mainly by the homeostatic process (sleep debt), the timing of sleep is orchestrated by the anterior hypothalamic suprachiasmatic nuclei (SCN). Disturbances in the organization of the sleep/wake cycle as well as circadian (approximately 24-hour periodicity) dysregulation are often noted in mental illness. The circadian rhythm of pineal melatonin secretion, which is controlled by the SCN, is reflective of mechanisms that are involved in the control of the sleep/wake cycle. Melatonin influences sleep-promoting and sleep/wake rhythm-regulating actions through the specific activation of melatonin (MT)1 and MT2 receptors, highly concentrated in the SCN. In healthy humans, melatonin induces sleep by a process influenced by the circadian phase. The hypnotic and rhythm-regulating properties of melatonin and its agonists (ramelteon, agomelatine) make them an important addition to the armamentarium of drugs for treating sleep disturbances and circadian rhythm sleep disorders associated with mental illness.