SleepA neurobiological model of insomnia
Introduction
Insomnia is defined by the symptoms of difficulty falling asleep, repeated awakenings with difficulty returning to sleep, or sleep that is nonrestorative or poor in quality, often accompanied by the perception of short overall sleep duration. Insomnia is the most common sleep-related symptom, with point prevalence ranging from 20 to 50% in most epidemiologic studies. Insomnia can also be more narrowly defined as a syndrome or disorder, that is, the complaint of insomnia accompanied by significant distress or daytime consequences such as irritability, impaired concentration or fatigue. When defined in this way, the prevalence of insomnia disorder is approximately 5–15% in the adult population [1, 2]. Implicit to either definition of insomnia is that the individual has adequate opportunity and circumstances for sleep, to distinguish it from sleep restriction/deprivation, which have different causes and consequences. Insomnia is associated with consistent risk factors including female sex, increasing age, concurrent depressive and anxiety symptoms and comorbid medical conditions [1]. Insomnia is often a chronic condition: longitudinal studies indicate that approximately 2/3 of individuals have symptoms which persist for at least one year [3]. Although often considered a nuisance symptom in clinical practice, insomnia has repeatedly been shown to be a risk factor for subsequent mental disorders, increased health care costs, occupational and social dysfunction, and impaired quality of life [4].
Historical references to insomnia date back thousands of years, but scientific investigation of the etiology and pathogenesis of insomnia has developed slowly. Several factors may account for this, including the heterogeneity of insomnia symptoms, the absence of an objectively defined phenotype and the discrepancy between self-report and objective sleep measures using polysomnography (PSG). In addition, insomnia has not lent itself well to the development of animal models, and the absence of molecular or genetic biomarkers makes in vitro models infeasible. Most models of insomnia have been based upon heuristically useful psychological and behavioral constructs [5]. However, recent developments in sleep neuroscience [6, 7] now make it possible to develop physiologically and neuroanatomically based models which complement the original models. After briefly summarizing psychological–behavioral models of insomnia and relevant sleep neurobiology, we propose a testable neurobiological model of insomnia.
Section snippets
Psychological–behavioral and neurocognitive models of insomnia
The diathesis-stress model proposed by Spielman et al. [8], more commonly known as the ‘3-P’ model, describes predisposing, precipitating and perpetuating factors relevant to the development and maintenance of insomnia. Predisposing factors include genetic, physiological or psychological diatheses that confer differential susceptibility to individuals. Precipitating factors include physiological, environmental or psychological stressors which push an individual over a hypothetical insomnia
Sleep-regulatory mechanisms
Although psychological–behavioral models have considerable utility, they lack neurobiological specificity. A brief review of sleep–wake neurobiology is important to understand the model we subsequently propose.
A proposed neurobiological model of insomnia
Our proposed neurobiological model of insomnia draws on previous psychological–behavioral models described in the first section of this paper, as well as the central and local neurobiological models of sleep regulation described in the second section. We hypothesize that insomnia is a disorder of sleep–wake regulation characterized by persistent wake-like activity in neural structures during NREM sleep, resulting in simultaneous and regionally specific waking and sleeping neuronal activity
Model comparison
The proposed neurobiological model of insomnia differs from the most widely cited models of insomnia primarily on the basis of level of inquiry. Most previous models have been developed from psychological and behavioral constructs which are measured by self-report or behavioral response patterns or global EEG characteristics. The neurobiological model has been developed from clinical and basic neuroscience observations which are measured in the activity patterns of more specific brain regions
Conclusions
Insomnia is a common clinical problem with important consequences for health and functioning. Previous models of insomnia, built primarily on psychological and behavioral constructs, conform well to reported symptoms and observed behaviors. However, these models have generally not proposed an underlying neural basis. The neurobiological model of insomnia builds on basic and clinical neuroscience findings, and combines aspects of traditional top-down and more recent local sleep models. We
Conflict of interest
Dr. Buysse has served as a paid consultant, and/or has received compensation for CME activities indirectly sponsored by the following companies: Actelion, Arena, Cephalon, Eli Lilly, GlaxoSmithKline, Merck, Neurocrine, Neurogen, Pfizer, Respironics, sanofi-aventis, Sepracor, Servier, Somnus Therapeutics, Stress Eraser, Takeda and Transcept Pharmaceuticals, Inc.
Acknowledgements
The authors gratefully acknowledge the staff at the Neuroscience Clinical and Translational Research Center of the University of Pittsburgh Clinical and Translational Research Center, who conducted polysomnographic studies, as well as the staff of the University of Pittsburgh PET Center.
Supported by National Institutes of Health grants MH024652, AG020677, MH061566 and RR024153.
References (38)
Insomnia: epidemiology and risk factors
Prevalence and perceived health associated with insomnia based on DSM-IV-TR; International Statistical Classification of Diseases and Related Health Problems, Tenth Revision; and Research Diagnostic Criteria/International Classification of Sleep Disorders. Second edition criteria: results from the America Insomnia Survey
Biol. Psychiatry
(2011)- et al.
Overview of insomnia: definitions, epidemiology, differential diagnosis, and assessment
Models of insomnia
- et al.
What brain imaging reveals about sleep generation and maintenance
A behavioral perspective on insomnia treatment
Psychiatr. Clin. N. Am.
(1987)A cognitive model of insomnia
Behav. Res. Ther.
(2002)The attention–intention-effort pathway in the development of psychophysiologic insomnia: a theoretical review
Sleep Med. Rev.
(2006)Neurobiology of waking and sleeping
Handb. Clin. Neurol.
(2011)Sleep state switching
Neuron
(2010)
Adenosine and sleep–wake regulation
Prog. Neurobiol.
Local functional state differences between rat cortical columns
Brain Res.
The natural history of insomnia: a population-based 3-year longitudinal study
Arch. Intern. Med.
Hypothalamic regulation of sleep and circadian rhythms
Nature
Stimulus control treatment for insomnia
Proc. Am. Psychol. Assoc.
Psychological and behavioral treatment of insomnia: an update of recent evidence (1998–2004)
Sleep
Sleep-related attentional bias in good, moderate, and poor (primary insomnia) sleepers
J. Abnorm. Psychol.
Sleep-related attentional bias in patients with primary insomnia compared with sleep experts and healthy controls
J. Sleep Res.
Psychophysiological insomnia: the behavioural model and a neurocognitive perspective
J. Sleep Res.
Cited by (128)
Social interaction anxiety and sleep quality in youth: Individual difference in childhood adversity and cardiac vagal control
2024, Journal of Affective DisordersIdentifying the insomnia-related psychological issues associated with hyperarousal: A network perspective
2024, International Journal of PsychophysiologyWhat is sleep exactly? Global and local modulations of sleep oscillations all around the clock
2023, Neuroscience and Biobehavioral ReviewsUnderstanding neuron-glia crosstalk and biological clocks in insomnia
2023, Neuroscience and Biobehavioral ReviewsAcute insomnia
2023, Encyclopedia of Sleep and Circadian Rhythms: Volume 1-6, Second EditionTypes of insomnia
2023, Encyclopedia of Sleep and Circadian Rhythms: Volume 1-6, Second Edition