Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Sleep and circadian rhythm disruption in psychiatric and neurodegenerative disease

Nature Reviews Neuroscience volume 11, pages 589–599 (2010)Cite this article

Subjects

Abstract

Sleep and circadian rhythm disruption are frequently observed in patients with psychiatric disorders and neurodegenerative disease. The abnormal sleep that is experienced by these patients is largely assumed to be the product of medication or some other influence that is not well defined. However, normal brain function and the generation of sleep are linked by common neurotransmitter systems and regulatory pathways. Disruption of sleep alters sleep–wake timing, destabilizes physiology and promotes a range of pathologies (from cognitive to metabolic defects) that are rarely considered to be associated with abnormal sleep. We propose that brain disorders and abnormal sleep have a common mechanistic origin and that many co-morbid pathologies that are found in brain disease arise from a destabilization of sleep mechanisms. The stabilization of sleep may be a means by which to reduce the symptoms of — and permit early intervention of — psychiatric and neurodegenerative disease.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Figure 1: The complex relationship between neuropathology (psychiatric disorder or neurodegenerative disease), an abnormal pattern of neurotransmitter release and circadian and sleep timing.
Figure 2: The health consequences of shortened or reduced sleep and desynchronized circadian rhythms, classified by emotional, cognitive and somatic responses.
Figure 3: Rest–activity profiles and hypnograms from two human subjects, illustrating normal and disrupted circadian behaviour.

References

  1. Kraeplin, E. Compendium der Psychiatrie zum Gebrauch fuer Studierende und Aerzte (Abel Verlag, Leipzig, 1883).

    Google Scholar 

  2. Papousek, M. [Chronobiological aspects of cyclothymia (author's transl)]. Fortschr. Neurol. Psychiatr. Grenzgeb. 43, 381–440 (1975).

    CAS  PubMed  Google Scholar 

  3. Wehr, T. A., Sack, D., Rosenthal, N., Duncan, W. & Gillin, J. C. Circadian rhythm disturbances in manic-depressive illness. Fed. Proc. 42, 2809–2814 (1983).

    CAS  PubMed  Google Scholar 

  4. Wirz-Justice, A., Puhringer, W. & Hole, G. Sleep deprivation and clomipramine in endogenous depression. Lancet 2, 912 (1976).

    Article  CAS  PubMed  Google Scholar 

  5. Wirz-Justice, A. et al. Sleep deprivation: effects on circadian rhythms of rat brain neurotransmitter receptors. Psychiatry Res. 5, 67–76 (1981).

    Article  CAS  PubMed  Google Scholar 

  6. Cirelli, C. The genetic and molecular regulation of sleep: from fruit flies to humans. Nature Rev. Neurosci. 10, 549–560 (2009).

    Article  CAS  Google Scholar 

  7. Wirz-Justice, A. Biological rhythm disturbances in mood disorders. Int. Clin. Psychopharmacol. 21, (Suppl. 1) 11–15 (2006).

    Article  Google Scholar 

  8. Wirz-Justice, A., Haug, H. J. & Cajochen, C. Disturbed circadian rest–activity cycles in schizophrenia patients: an effect of drugs? Schizophr. Bull. 27, 497–502 (2001).

    Article  CAS  PubMed  Google Scholar 

  9. Smith, M. T., Perlis, M. L., Smith, M. S., Giles, D. E. & Carmody, T. P. Sleep quality and presleep arousal in chronic pain. J. Behav. Med. 23, 1–13 (2000).

    Article  CAS  PubMed  Google Scholar 

  10. Takahashi, J. S., Hong, H. K., Ko, C. H. & McDearmon, E. L. The genetics of mammalian circadian order and disorder: implications for physiology and disease. Nature Rev. Genet. 9, 764–775 (2008).

    Article  CAS  PubMed  Google Scholar 

  11. Mieda, M. & Sakurai, T. Integrative physiology of orexins and orexin receptors. CNS Neurol. Disord. Drug Targets 8, 281–295 (2009).

    Article  CAS  PubMed  Google Scholar 

  12. Feder, A., Nestler, E. J. & Charney, D. S. Psychobiology and molecular genetics of resilience. Nature Rev. Neurosci. 10, 446–457 (2009).

    Article  CAS  Google Scholar 

  13. Wulff, K., Porcheret, K., Cussans, E. & Foster, R. G. Sleep and circadian rhythm disturbances: multiple genes and multiple phenotypes. Curr. Opin. Genet. Dev. 19, 237–246 (2009).

    Article  CAS  PubMed  Google Scholar 

  14. Armitage, R. Sleep and circadian rhythms in mood disorders. Acta Psychiatr. Scand. Suppl. 115, 104–115 (2007).

    Article  Google Scholar 

  15. Schibler, U. The daily timing of gene expression and physiology in mammals. Dialogues Clin. Neurosci. 9, 257–272 (2007).

    PubMed  PubMed Central  Google Scholar 

  16. Katz, G., Durst, R., Zislin, Y., Barel, Y. & Knobler, H. Y. Psychiatric aspects of jet lag: review and hypothesis. Med. Hypotheses 56, 20–23 (2001).

    Article  CAS  PubMed  Google Scholar 

  17. Benedetti, F., Barbini, B., Colombo, C. & Smeraldi, E. Chronotherapeutics in a psychiatric ward. Sleep Med. Rev. 11, 509–522 (2007).

    Article  PubMed  Google Scholar 

  18. Wirz-Justice, A. & Van den Hoofdakker, R. H. Sleep deprivation in depression: what do we know, where do we go? Biol. Psychiatry 46, 445–453 (1999).

    Article  CAS  PubMed  Google Scholar 

  19. Bunney, J. N. & Potkin, S. G. Circadian abnormalities, molecular clock genes and chronobiological treatments in depression. Br. Med. Bull. 86, 23–32 (2008).

    Article  CAS  PubMed  Google Scholar 

  20. Pigeon, W. R. et al. Is insomnia a perpetuating factor for late-life depression in the IMPACT cohort? Sleep 31, 481–488 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  21. Posmontier, B. Sleep quality in women with and without postpartum depression. J. Obstet. Gynecol. Neonatal Nurs. 37, 722–735; (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  22. Asnis, G. M. et al. Zolpidem for persistent insomnia in SSRI-treated depressed patients. J. Clin. Psychiatry 60, 668–676 (1999).

    Article  CAS  PubMed  Google Scholar 

  23. Krystal, A. D., Thakur, M. & Roth, T. Sleep disturbance in psychiatric disorders: effects on function and quality of life in mood disorders, alcoholism, and schizophrenia. Ann. Clin. Psychiatry 20, 39–46 (2008).

    Article  PubMed  Google Scholar 

  24. Kasper, S. et al. Efficacy of the novel antidepressant agomelatine on the circadian rest-activity cycle and depressive and anxiety symptoms in patients with major depressive disorder: a randomized, double-blind comparison with sertraline. J. Clin. Psychiatry 71, 109–120 (2010).

    Article  CAS  PubMed  Google Scholar 

  25. Lopes, M. C., Quera-Salva, M. A. & Guilleminault, C. Non-REM sleep instability in patients with major depressive disorder: subjective improvement and improvement of non-REM sleep instability with treatment (Agomelatine). Sleep Med. 9, 33–41 (2007).

    Article  PubMed  Google Scholar 

  26. Olie, J. P. & Kasper, S. Efficacy of agomelatine, a MT1/MT2 receptor agonist with 5-HT2C antagonistic properties, in major depressive disorder. Int. J. Neuropsychopharmacol. 10, 661–673 (2007).

    CAS  PubMed  Google Scholar 

  27. Quera-Salva, M. A., Lemoine, P. & Guilleminault, C. Impact of the novel antidepressant agomelatine on disturbed sleep–wake cycles in depressed patients. Hum. Psychopharmacol. 25, 222–229 (2010).

    Article  CAS  PubMed  Google Scholar 

  28. Fava, M. et al. Modafinil augmentation of selective serotonin reuptake inhibitor therapy in MDD partial responders with persistent fatigue and sleepiness. Ann. Clin. Psychiatry 19, 153–159 (2007).

    Article  PubMed  Google Scholar 

  29. Kupfer, D. J. et al. REM sleep, naps, and depression. Psychiatry Res. 5, 195–203 (1981).

    Article  CAS  PubMed  Google Scholar 

  30. Modell, S., Huber, J., Holsboer, F. & Lauer, C. J. The munich vulnerability study on affective disorders: risk factors for unipolarity versus bipolarity. J. Affect. Disord. 74, 173–184 (2003).

    Article  PubMed  Google Scholar 

  31. Rao, U. et al. Heterogeneity in EEG sleep findings in adolescent depression: unipolar versus bipolar clinical course. J. Affect. Disord. 70, 273–280 (2002).

    Article  PubMed  Google Scholar 

  32. Gregory, A. M., Cox, J., Crawford, M. R., Holland, J. & Haravey, A. G. Dysfunctional beliefs and attitudes about sleep in children. J. Sleep Res. 18, 422–426 (2009).

    Article  PubMed  Google Scholar 

  33. Levitt, A. J. & Boyle, M. H. The impact of latitude on the prevalence of seasonal depression. Can. J. Psychiatry 47, 361–367 (2002).

    Article  PubMed  Google Scholar 

  34. Axelsson, J., Ragnarsdottir, S., Pind, J. & Sigbjornsson, R. Daylight availability: a poor predictor of depression in Iceland. Int. J. Circumpolar Health 63, 267–276 (2004).

    Article  PubMed  Google Scholar 

  35. Wirz-Justice, A. Chronobiology and psychiatry. Sleep Med. Rev. 11, 423–427 (2007).

    Article  PubMed  Google Scholar 

  36. Lavoie, M. P. et al. Evidence of a biological effect of light therapy on the retina of patients with seasonal affective disorder. Biol. Psychiatry 66, 253–258 (2009).

    Article  PubMed  Google Scholar 

  37. Hankins, M. W., Peirson, S. N. & Foster, R. G. Melanopsin: an exciting photopigment. Trends Neurosci. 31, 27–36 (2008).

    Article  CAS  PubMed  Google Scholar 

  38. McClung, C. A. Circadian genes, rhythms and the biology of mood disorders. Pharmacol. Ther. 114, 222–232 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Plante, D. T. & Winkelman, J. W. Sleep disturbance in bipolar disorder: therapeutic implications. Am. J. Psychiatry 165, 830–843 (2008).

    Article  PubMed  Google Scholar 

  40. Young, A. H. Antiglucocoticoid treatments for depression. Aust. N. Z. J. Psychiatry 40, 402–405 (2006).

    Article  PubMed  Google Scholar 

  41. Roybal, K. et al. Mania-like behavior induced by disruption of CLOCK. Proc. Natl Acad. Sci. USA 104, 6406–6411 (2007).

    Article  CAS  PubMed  Google Scholar 

  42. Salvatore, P. et al. Circadian activity rhythm abnormalities in ill and recovered bipolar I disorder patients. Bipolar Disord. 10, 256–265 (2008).

    Article  PubMed  Google Scholar 

  43. Benedetti, F. et al. A length polymorphism in the circadian clock gene Per3 influences age at onset of bipolar disorder. Neurosci. Lett. 445, 184–187 (2008).

    Article  CAS  PubMed  Google Scholar 

  44. Bellivier, F. et al. Age at onset in bipolar I affective disorder: further evidence for three subgroups. Am. J. Psychiatry 160, 999–1001 (2003).

    Article  PubMed  Google Scholar 

  45. Conus, P. et al. The proximal prodrome to first episode mania — a new target for early intervention. Bipolar Disord. 10, 555–565 (2008).

    Article  PubMed  Google Scholar 

  46. Modell, S., Ising, M., Holsboer, F. & Lauer, C. J. The Munich vulnerability study on affective disorders: premorbid polysomnographic profile of affected high-risk probands. Biol. Psychiatry 58, 694–699 (2005).

    Article  PubMed  Google Scholar 

  47. Roehrs, T. & Roth, T. Sleep, sleepiness, sleep disorders and alcohol use and abuse. Sleep Med. Rev. 5, 287–297 (2001).

    Article  PubMed  Google Scholar 

  48. Krystal, A. D. Treating the health, quality of life, and functional impairments in insomnia. J. Clin. Sleep Med. 3, 63–72 (2007).

    PubMed  Google Scholar 

  49. Hatonen, T., Forsblom, S., Kieseppa, T., Lonnqvist, J. & Partonen, T. Circadian phenotype in patients with the co-morbid alcohol use and bipolar disorders. Alcohol Alcohol. 43, 564–568 (2008).

    Article  PubMed  Google Scholar 

  50. Spanagel, R. et al. The clock gene Per2 influences the glutamatergic system and modulates alcohol consumption. Nature Med. 11, 35–42 (2005).

    Article  CAS  PubMed  Google Scholar 

  51. Franken, P., Thomason, R., Heller, H. C. & O'Hara, B. F. A non-circadian role for clock-genes in sleep homeostasis: a strain comparison. BMC Neurosci. 8, 87 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Rodd, Z. A. et al. Candidate genes, pathways and mechanisms for alcoholism: an expanded convergent functional genomics approach. Pharmacogenomics J. 7, 222–256 (2007).

    Article  CAS  PubMed  Google Scholar 

  53. Francks, C. et al. Population-based linkage analysis of schizophrenia and bipolar case-control cohorts identifies a potential susceptibility locus on 19q13. Mol. Psychiatry 15, 319–325 (2008).

    Article  CAS  PubMed  Google Scholar 

  54. Hendler, T., Bleich-Cohen, M. & Sharon, H. Neurofunctional view of psychiatry: clinical brain imaging revisited. Curr. Opin. Psychiatry 22, 300–305 (2009).

    Article  PubMed  Google Scholar 

  55. Stahl, S. M. & Buckley, P. F. Negative symptoms of schizophrenia: a problem that will not go away. Acta Psychiatr. Scand. 115, 4–11 (2007).

    Article  CAS  PubMed  Google Scholar 

  56. Van Cauter, E. et al. Circadian and sleep-related endocrine rhythms in schizophrenia. Arch Gen Psychiatry 48, 348–356 (1991).

    Article  CAS  PubMed  Google Scholar 

  57. Cohrs, S. Sleep disturbances in patients with schizophrenia: impact and effect of antipsychotics. CNS Drugs 22, 939–962 (2008).

    Article  CAS  PubMed  Google Scholar 

  58. Auslander, L. A. & Jeste, D. V. Perceptions of problems and needs for service among middle-aged and elderly outpatients with schizophrenia and related psychotic disorders. Community Ment. Health J. 38, 391–402 (2002).

    Article  PubMed  Google Scholar 

  59. Hofstetter, J. R., Lysaker, P. H. & Mayeda, A. R. Quality of sleep in patients with schizophrenia is associated with quality of life and coping. BMC Psychiatry 5, 13 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  60. Tomppo, L. et al. Association of variants in DISC1 with psychosis-related traits in a large population cohort. Arch. Gen. Psychiatry 66, 134–141 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  61. Sawamura, N. et al. Nuclear DISC1 regulates CRE-mediated gene transcription and sleep homeostasis in the fruit fly. Mol. Psychiatry 13, 1138–1148 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Gottlieb, D. J., O'Connor, G. T. & Wilk, J. B. Genome-wide association of sleep and circadian phenotypes. BMC Med. Genet. 8, (Suppl. 1) 9 (2007).

    Article  CAS  Google Scholar 

  63. Tomppo, L. et al. Association between genes of disrupted in schizophrenia 1 (DISC1) interactors and schizophrenia supports the role of the DISC1 pathway in the etiology of major mental illnesses. Biol. Psychiatry 65, 1055–1062 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Takao, T., Tachikawa, H., Kawanishi, Y., Mizukami, K. & Asada, T. CLOCK gene T3111C polymorphism is associated with Japanese schizophrenics: a preliminary study. Eur. Neuropsychopharmacol. 17, 3273–3276 (2007).

    Article  CAS  Google Scholar 

  65. Ding, J. M. et al. Resetting the biological clock: mediation of nocturnal circadian shifts by glutamate and NO. Science 266, 1713–1717 (1994).

    Article  CAS  PubMed  Google Scholar 

  66. Young, C. E. et al. SNAP-25 deficit and hippocampal connectivity in schizophrenia. Cereb. Cortex 8, 261–268 (1998).

    Article  CAS  PubMed  Google Scholar 

  67. Oliver, P. L. & Davies, K. E. Interaction between environmental and genetic factors modulates schizophrenic endophenotypes in the Snap-25 mouse mutant blind–drunk. Hum. Mol. Genet. 18, 4576–4589 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Deery, M. J. et al. Proteomic analysis reveals the role of synaptic vesicle cycling in sustaining the suprachiasmatic circadian clock. Curr. Biol. 19, 2031–2036 (2009).

    Article  CAS  PubMed  Google Scholar 

  69. Monti, J. M. & Monti, D. Sleep disturbance in generalized anxiety disorder and its treatment. Sleep Med. Rev. 4, 263–276 (2000).

    Article  PubMed  Google Scholar 

  70. Papadimitriou, G. N. & Linkowski, P. Sleep disturbance in anxiety disorders. Int. Rev. Psychiatry 17, 229–236 (2005).

    Article  PubMed  Google Scholar 

  71. Xu, Y. L. et al. Neuropeptide S: a neuropeptide promoting arousal and anxiolytic-like effects. Neuron 43, 487–497 (2004).

    Article  CAS  PubMed  Google Scholar 

  72. Reinscheid, R. K. & Xu, Y. L. Neuropeptide S as a novel arousal promoting peptide transmitter. FEBS J. 272, 5689–5693 (2005).

    Article  CAS  PubMed  Google Scholar 

  73. Okamura, N. & Reinscheid, R. K. Neuropeptide S: a novel modulator of stress and arousal. Stress 10, 221–226 (2007).

    Article  CAS  PubMed  Google Scholar 

  74. Leonard, S. K. et al. Pharmacology of neuropeptide S. in mice: therapeutic relevance to anxiety disorders. Psychopharmacology (Berlin) 197, 601–611 (2008).

    Article  CAS  Google Scholar 

  75. Reinscheid, R. K. Neuropeptide S: anatomy, pharmacology, genetics and physiological functions. Results Probl. Cell Differ. 46, 145–158 (2008).

    Article  CAS  PubMed  Google Scholar 

  76. Okamura, N. et al. Gender-specific association of a functional coding polymorphism in the Neuropeptide S receptor gene with panic disorder but not with schizophrenia or attention-deficit/hyperactivity disorder. Prog. Neuropsychopharmacol. Biol. Psychiatry 31, 1444–1448 (2007).

    Article  CAS  PubMed  Google Scholar 

  77. Bohnen, N. I. & Albin, R. L. The cholinergic system and Parkinson disease. Behav. Brain Res. 7 Jan 2010 (doi:10.1016/j.bbr.2009.12.048).

  78. Jeong, J. EEG dynamics in patients with Alzheimer's disease. Clin. Neurophysiol. 115, 1490–1505 (2004).

    Article  PubMed  Google Scholar 

  79. Hofman, M. A. & Swaab, D. F. Alterations in circadian rhythmicity of the vasopressin-producing neurons of the human suprachiasmatic nucleus (SCN) with aging. Brain Res. 651, 134–142 (1994).

    Article  CAS  PubMed  Google Scholar 

  80. Vitiello, M. V., Prinz, P. N., Williams, D. E., Frommlet, M. S. & Ries, R. K. Sleep disturbances in patients with mild-stage Alzheimer's disease. J. Gerontol. 45, M131–M138 (1990).

    Article  CAS  PubMed  Google Scholar 

  81. Clemens, Z., Fabo, D. & Halasz, P. Overnight verbal memory retention correlates with the number of sleep spindles. Neuroscience 132, 529–535 (2005).

    Article  CAS  PubMed  Google Scholar 

  82. Tractenberg, R. E., Singer, C. M. & Kaye, J. A. Characterizing sleep problems in persons with Alzheimer's disease and normal elderly. J. Sleep Res. 15, 97–103 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  83. Zhou, J. N., Liu, R. Y., Kamphorst, W., Hofman, M. A. & Swaab, D. F. Early neuropathological Alzheimer's changes in aged individuals are accompanied by decreased cerebrospinal fluid melatonin levels. J. Pineal Res. 35, 125–130 (2003).

    Article  CAS  PubMed  Google Scholar 

  84. Rajaratnam, S. M. & Arendt, J. Health in a 24-h society. Lancet 358, 999–1005 (2001).

    Article  CAS  PubMed  Google Scholar 

  85. Dowling, G. A. et al. Melatonin and bright-light treatment for rest-activity disruption in institutionalized patients with Alzheimer's disease. J. Am. Geriatr. Soc. 56, 239–246 (2008).

    Article  PubMed  Google Scholar 

  86. Parkinson, J. An essay on the shaking palsy. 1817. J. Neuropsychiatry Clin. Neurosci. 14, 223–236 (2002); discussion in 14, 222 (2002).

    Article  Google Scholar 

  87. Arnulf, I., Leu, S. & Oudiette, D. Abnormal sleep and sleepiness in Parkinson's disease. Curr. Opin. Neurol. 21, 472–477 (2008).

    Article  PubMed  Google Scholar 

  88. Willis, G. L., Kelly, A. M. & Kennedy, G. A. Compromised circadian function in Parkinson's disease: enucleation augments disease severity in the unilateral model. Behav. Brain Res. 193, 37–47 (2008).

    Article  CAS  PubMed  Google Scholar 

  89. Metzler-Baddeley, C. A review of cognitive impairments in dementia with Lewy bodies relative to Alzheimer's disease and Parkinson's disease with dementia. Cortex 43, 583–600 (2007).

    Article  PubMed  Google Scholar 

  90. Kassubek, J. et al. Topography of cerebral atrophy in early Huntington's disease: a voxel based morphometric MRI study. J. Neurol. Neurosurg. Psychiatry 75, 213–220 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Rosas, H. D. et al. Evidence for more widespread cerebral pathology in early HD: an MRI-based morphometric analysis. Neurology 60, 1615–1620 (2003).

    Article  CAS  PubMed  Google Scholar 

  92. Morton, A. J. et al. Disintegration of the sleep–wake cycle and circadian timing in Huntington's disease. J. Neurosci. 25, 157–163 (2005).

    Article  CAS  PubMed  Google Scholar 

  93. Goodman, A. O. & Barker, R. A. How vital is sleep in Huntington's disease? J. Neurol. 257, 882–897 (2010).

    Article  CAS  PubMed  Google Scholar 

  94. Pallier, P. N. et al. Pharmacological imposition of sleep slows cognitive decline and reverses dysregulation of circadian gene expression in a transgenic mouse model of Huntington's disease. J. Neurosci. 27, 7869–7878 (2007).

    Article  CAS  PubMed  Google Scholar 

  95. Pallier, P. N. & Morton, A. J. Management of sleep/wake cycles improves cognitive function in a transgenic mouse model of Huntington's disease. Brain Res. 1279, 90–98 (2009).

    Article  CAS  PubMed  Google Scholar 

  96. Taphoorn, M. J. et al. Fatigue, sleep disturbances and circadian rhythm in multiple sclerosis. J. Neurol. 240, 446–448 (1993).

    Article  CAS  PubMed  Google Scholar 

  97. Attarian, H. P., Brown, K. M., Duntley, S. P., Carter, J. D. & Cross, A. H. The relationship of sleep disturbances and fatigue in multiple sclerosis. Arch. Neurol. 61, 525–528 (2004).

    Article  PubMed  Google Scholar 

  98. Gallup, A. C., Gallup, G. G. Jr. & Feo, C. Yawning, sleep, and symptom relief in patients with multiple sclerosis. Sleep Med. 11, 329–330 (2010).

    Article  PubMed  Google Scholar 

  99. Mendozzi, L., Tronci, F., Garegnani, M. & Pugnetti, L. Sleep disturbance and fatigue in mild relapsing remitting multiple sclerosis patients on chronic immunomodulant therapy: an actigraphic study. Mult. Scler. 16, 238–247 (2010).

    Article  PubMed  Google Scholar 

  100. Ceccarelli, A. et al. T2 hypointensity in the deep gray matter of patients with benign multiple sclerosis. Mult. Scler. 15, 678–686 (2009).

    Article  CAS  PubMed  Google Scholar 

  101. Auer, R. N., Rowlands, C. G., Perry, S. F. & Remmers, J. E. Multiple sclerosis with medullary plaques and fatal sleep apnea (Ondine's curse). Clin. Neuropathol. 15, 101–105 (1996).

    CAS  PubMed  Google Scholar 

  102. Wirz-Justice, A., Benedetti, F. & Terman, M. Chronotherapeutics for Affective Disorders (Karger, Basel, 2009).

    Book  Google Scholar 

  103. Damiola, F. et al. Restricted feeding uncouples circadian oscillators in peripheral tissues from the central pacemaker in the suprachiasmatic nucleus. Genes Dev. 14, 2950–2961 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Goetz, F. et al. Timing of single daily meal influences relations among human circadian rhythms in urinary cyclic AMP and hemic glucagon, insulin and iron. Experientia 32, 1081–1084 (1976).

    Article  CAS  PubMed  Google Scholar 

  105. Riemann, D. et al. The hyperarousal model of insomnia: a review of the concept and its evidence. Sleep Med. Rev. 14, 19–31 (2010).

    Article  PubMed  Google Scholar 

  106. Pace-Schott, E. F. & Hobson, J. A. The neurobiology of sleep: genetics, cellular physiology and subcortical networks. Nature Rev. Neurosci. 3, 591–605 (2002).

    Article  CAS  Google Scholar 

  107. Diniz Behn, C. G., Kopell, N., Brown, E. N., Mochizuki, T. & Scammell, T. E. Delayed orexin signaling consolidates wakefulness and sleep: physiology and modeling. J. Neurophysiol. 99, 3090–3103 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Behn, C. G., Brown, E. N., Scammell, T. E. & Kopell, N. J. Mathematical model of network dynamics governing mouse sleep-wake behavior. J. Neurophysiol. 97, 3828–3840 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  109. Lockley, S. W. et al. Short-wavelength sensitivity for the direct effects of light on alertness, vigilance, and the waking electroencephalogram in humans. Sleep 29, 161–168 (2006).

    Google Scholar 

  110. Scheer, F. A., Wright, K. P. Jr, Kronauer, R. E. & Czeisler, C. A. Plasticity of the intrinsic period of the human circadian timing system. PLoS ONE 2, e721 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  111. Meijer, J. H., Michel, S. & Vansteensel, M. J. Processing of daily and seasonal light information in the mammalian circadian clock. Gen. Comp. Endocrinol. 152, 159–164 (2007).

    Article  CAS  PubMed  Google Scholar 

  112. Buijs, R. M., van Eden, C. G., Goncharuk, V. D. & Kalsbeek, A. The biological clock tunes the organs of the body: timing by hormones and the autonomic nervous system. J. Endocrinol. 177, 17–26 (2003).

    Article  CAS  PubMed  Google Scholar 

  113. Lupi, D., Oster, H., Thompson, S. & Foster, R. G. The acute light-induction of sleep is mediated by OPN4-based photoreception. Nature Neurosci. 11, 1068–1073 (2008).

    Article  CAS  PubMed  Google Scholar 

  114. Ko, C. H. & Takahashi, J. S. Molecular components of the mammalian circadian clock. Hum. Mol. Genet. 15, R271–R277 (2006).

    Article  CAS  PubMed  Google Scholar 

  115. Schibler, U. The 2008 Pittendrigh/Aschoff lecture: peripheral phase coordination in the mammalian circadian timing system. J. Biol. Rhythms 24, 3–15 (2009).

    Article  CAS  PubMed  Google Scholar 

  116. Corradini, I., Verderio, C., Sala, M., Wilson, M. C. & Matteoli, M. SNAP-25 in neuropsychiatric disorders. Ann. N. Y. Acad. Sci. 1152, 93–99 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Yi, C. X. et al. Ventromedial arcuate nucleus communicates peripheral metabolic information to the suprachiasmatic nucleus. Endocrinology 147, 283–294 (2006).

    Article  CAS  PubMed  Google Scholar 

  118. Malek, Z. S., Sage, D., Pevet, P. & Raison, S. Daily rhythm of tryptophan hydroxylase-2 messenger ribonucleic acid within raphe neurons is induced by corticoid daily surge and modulated by enhanced locomotor activity. Endocrinology 148, 5165–5172 (2007).

    Article  CAS  PubMed  Google Scholar 

  119. He, Y. et al. The transcriptional repressor DEC2 regulates sleep length in mammals. Science 325, 866–870 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Maywood, E. S., O'Neill, J. S., Chesham, J. E. & Hastings, M. H. Minireview: the circadian clockwork of the suprachiasmatic nuclei — analysis of a cellular oscillator that drives endocrine rhythms. Endocrinology 148, 5624–5634 (2007).

    Article  CAS  PubMed  Google Scholar 

  121. Godinho, S. I. et al. The after-hours mutant reveals a role for Fbxl3 in determining mammalian circadian period. Science 316, 897–900 (2007).

    Article  CAS  PubMed  Google Scholar 

  122. Dijk, D. J. & Archer, S. N. PERIOD3, circadian phenotypes, and sleep homeostasis. Sleep Med. Rev. 14, 151–160 (2010).

    Article  PubMed  Google Scholar 

  123. Reghunandanan, V. & Reghunandanan, R. Neurotransmitters of the suprachiasmatic nuclei. J. Circadian Rhythms 4, 2 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The work is supported by the National Institute for Health Research (NIHR). Biomedical Research Centre, Oxford, UK, and The Wellcome Trust, London, UK. We would like to thank G. Goodwin (head of the Department of Psychiatry, University of Oxford, UK), C. Kennard (head of the Department of Clinical Neurology, University of Oxford, UK), K. Porcheret (Nuffield Laboratory of Ophthalmology, University of Oxford, UK), K. Davies and P. Oliver (Medical Research Council Functional Genomics Unit, University of Oxford, UK) for their valuable input during the preparation of this manuscript.

Author information

Author notes

  1. Katharina Wulff and Russell G. Foster: Katharina Wulff and Russell G. Foster are members of the Circadian and Visual Neuroscience group, Nuffield Laboratory of Ophthalmology, University of Oxford, Headley Way, Oxford, OX3 9DU, UK.

Authors and Affiliations

  1. Silvia Gatti and Joseph G. Wettstein are at the Neuroscience Research, F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland.,

    Silvia Gatti, Joseph G. Wettstein & Russell G. Foster

Authors
  1. Katharina Wulff
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Silvia Gatti
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joseph G. Wettstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Russell G. Foster
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Russell G. Foster.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary information S1 (table)

Circadian/sleep-related abnormalities observed in a range of syndromes with some emerging sleep/circadian genetic associations (PDF 441 kb)

Supplementary information S2 (table)

references for Figure 3 on the health consequences of shortened/disrupted sleep and circadian rhythms. (PDF 421 kb)

Related links

Related links

FURTHER INFORMATION

Author's homepage

Glossary

Bipolar disorder

A disorder characterized by abrupt mixed states of mood from an energetic elevated mood (termed mania or, if milder, hypomania) to a deep depressive state. Bipolar disorder type 1 classification is based on the occurrence of at least one manic episode, with or without the occurrence of a major depressive episode. Bipolar disorder type 2 is characterized by at least one hypomania episode and one major depressive state.

Chronotype

An individual's preference for daytime or night-time activities (also referred to as morningness and eveningness or larks and owls, respectively). Morning types wake up early and are most alert in the first part of the day, whereas evening types are most alert in the late evening hours and prefer to go to bed late.

Circadian phase

A particular reference point in the circadian cycle. For example, the onset of sleep.

Circadian system

(Also known as process C). The entire molecular, cellular and physiological basis for the generation of circadian rhythms in an organism.

Diagnostic and statistical manual of mental disorders

(DSM-IV). A manual published by the American Psychiatric Association that provides diagnostic criteria for mental health disorders. DSM-IV-TR is the most recent, text-revised version published in 2000.

Diurnal

An activity or process that occurs during the daytime (during light).

Electroencephalography

(EEG). A measure of the electrical activity of the brain that can be used to define different wake, NREM and REM sleep states.

Endophenotype

A special type of biomarker. In mental health, it is the division of behavioural symptoms into recognizable phenotypes with a clear genetic association.

Entrainment

The process by which an organism's circadian rhythm is synchronized to an environmental rhythm such as the light–dark cycle.

Hypothalamic-pituitary-adrenal axis

A complex set of direct influences and feedback interactions among the hypothalamus, pituitary gland and adrenal glands. The hypothalamic-pituitary-adrenal (HPA) axis constitutes a major part of the neuroendocrine system that controls reactions to stress.

International Classification of Disorders

(ICD-10). A disease classification published by the World Health Organization that provides diagnostic criteria for mental health disorders. The ICD-10 classification consists of 10 main groups.

K complexes

A brief, negative high-voltage peak, usually greater than 100 μV. Like sleep spindles, K-complexes are another characteristic of stage two sleep.

Light therapy

(Also known as phototherapy). Consists of exposure to daylight or artificial light (provided by a light box). Light exposure is of a defined intensity and is given at a specific time. Light therapy has been used to treat circadian rhythm disorders, such as delayed sleep phase syndrome, and can also be used to treat seasonal affective disorder.

Major depressive disorder

A disorder characterized by severe, highly persistent depression and a loss of interest or pleasure in everyday activities. It is often associated with lack of appetite, chronic fatigue and sleep disturbances. There is an increased risk of suicide.

Narcolepsy

A chronic sleep disorder (or dyssomnia). In relation to sleep, the condition is characterized by excessive daytime sleepiness whereby the individual experiences extreme fatigue at inappropriate times and may fall asleep.

Non-rapid eye movement sleep

(NREM). There are four distinct stages of NREM sleep (NREM 1–4) defined on the basis of EEG or polysomnography and other characteristics that are seen in each stage.

Prodromal

An early symptom (or set of symptoms) that might indicate the start of a disease before specific symptoms occur.

Selective serotonin reuptake inhibitors

(Also known as serotonin-specific reuptake inhibitors). A class of compounds typically used as antidepressants in the treatment of depression, anxiety disorders and some personality disorders. These inhibitors increase the extracellular level of the neurotransmitter serotonin by inhibiting its reuptake into the presynaptic cell. This increases the level of serotonin that is available to bind to the postsynaptic receptor.

Sleep spindles

Stage 2 sleep is characterized by sleep spindles that signify a burst of brain activity which is visible on an electroencephalogram (EEG) ranging from 11 to 16 Hz.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Wulff, K., Gatti, S., Wettstein, J. et al. Sleep and circadian rhythm disruption in psychiatric and neurodegenerative disease. Nat Rev Neurosci 11, 589–599 (2010). https://doi.org/10.1038/nrn2868

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrn2868

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing