Pathophysiology of sleep disorders

Abstract

Current concepts on neurobiological mechanisms underlying sleep disorders such as insomnia, narcolepsy, and restless legs syndrome/periodic limb movement disorder are being reviewed in this chapter, which includes short discussions of clinical key features, diagnostic criteria, and therapeutic aspects of these disorders. Chronic insomnia is a common and complex 24-h disorder that derives from a multifactorial interaction of biological and psychological factors affecting both sleep and wakefulness. Several models of the pathophysiology of insomnia have been elaborated, but no single underlying pathophysiological process has been shown to represent a causal factor. Importantly, persistent insomnia has been identified as a risk factor for the development or exacerbation of certain psychiatric conditions. Narcolepsy is characterized by excessive daytime sleepiness and cataplexy. Its pathophysiology is largely associated with hypocretin ligand deficiency possibly caused by the postnatal loss of hypocretin-containing neurons. An immune-mediated etiology for hypocretin deficiency has been suggested. Sleep-related movement disorders include the restless legs syndrome (RLS) and periodic limb movement disorder (PLMD). Pharmacological, neuroimaging, and electrophysiological studies suggest a dysfunction of the supraspinal inhibitory system triggering RLS and PLMD. In addition, recent studies suggest a strong genetic contribution to both disorders. Further research on sleep disorders is expected to guide new treatment strategies.