Molecular mechanisms of the sleep wake cycle : therapeutic applications to insomnia

Abstract

The aim of this review is to explore the molecular mechanism and genetic components of the sleepwake cycle and insomnia. Moreover, we wanted to review the correlation between primary insomnia and its comorbidities. With this aim, a systematic review of recent evidence of the molecular and genetic mechanisms involved in the causation of primary insomnia, along with associations between primary insomnia and other diseases were conducted. Primary insomnia is a complex disorder which accounts for 25% of total chronic insomnia and has several effects other than on sleep. It is manifested by a variety of genetic, cultural, social, psychological and environmental factors. Chronic insomnia has been shown to be 24-hour hyperarousal with reduced relative metabolism in the prefrontal cortex while awake. Insomnia can cause various physiological effects and memory capacity alterations; with chronic activation of the hypothalamic–pituitary–adrenal axis also leading to the development of depression and anxiety. Orexins and melatonin are important regulators of sleep and wakefulness. Detailed mechanisms of alterations to the neuroendocrine components highlight the therapeutic potential of orexin antagonists, as well as exogenous melatonin and melatonin receptor agonists. Genetics plays an important role in the development of insomnia, with several single nucleotide polymorphisms implicated in sleep regulation. Further research is crucial to aid understanding of this common disorder and enhance treatment options.