title: Human physiological models of insomnia.
abstract: Despite the wide prevalence and important consequences of insomnia, remarkably little is known about its pathophysiology. Available models exist primarily in the psychological domain and derive from the demonstrated efficacy of behavioral treatment approaches to insomnia management. However, these models offer little specific prediction about the anatomic or physiological foundation of chronic primary insomnia. On the other hand, a growing body of data on the physiology of sleep supports a reasonably circumscribed overview of possible pathophysiological mechanisms, as well as the development of physiological models of insomnia to guide future research. As a pragmatic step, these models focus on primary insomnia, as opposed to comorbid insomnias, because the latter is by its nature a much more heterogeneous presentation, reflecting the effects of the distinct comorbid condition. Current understanding of the regulation of sleep and wakefulness in mammalian brain supports four broad candidate areas: 1) disruption of the sleep homeostat; 2) disruption of the circadian clock; 3) disruption of intrinsic systems responsible for the expression of sleep states; or 4) disruption (hyperactivity) of extrinsic systems capable of over-riding normal sleep-wake regulation. This review examines each of the four candidate pathophysiological mechanisms and the available data in support of each. While studies that directly test the viability of each model are not yet available, descriptive data on primary insomnia favor the involvement of dysfunctional extrinsic stress-response systems in the pathology of primary chronic insomnia.
authors.affiliation: Sleep Research Laboratory, Henry Ford Hospital, Detroit, MI, USA. grichar1@hfhs.org
authors.forename: Gary S
authors.initials: GS
authors.lastname: Richardson
mesh_terms: D001143:Arousal / Q000502:physiology; D001921:Brain / Q000502:physiology*; D002908:Chronic Disease; D019317:Evidence-Based Medicine; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D012890:Sleep / Q000502:physiology; D007319:Sleep Initiation and Maintenance Disorders / Q000503:physiopathology*; D012894:Sleep Stages / Q000502:physiology; D012895:Sleep, REM / Q000502:physiology; D014851:Wakefulness / Q000502:physiology