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Insights from studying human sleep disorders

Nature volume 437, pages 1279–1285 (2005)Cite this article

Abstract

Problems with sleep are one of the commonest reasons for seeking medical attention. Knowledge gained from basic research into sleep in animals has led to marked advances in the understanding of human sleep, with important diagnostic and therapeutic implications. At the same time, research guided by human sleep disorders is leading to important basic sleep concepts. For example, sleep may not be a global, but rather a local, brain phenomenon. Furthermore, contrary to common assumptions, wakefulness, rapid eye movement (REM) and non-REM sleep are not mutually exclusive states. This striking realization explains a fascinating range of clinical phenomena.

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Figure 1: Ambiguous sleep in a patient with narcolepsy.
Figure 2: A sleepwalking episode.
Figure 3: The rapid evolution of a sleep terror episode.
Figure 4: REM sleep behaviour disorder.
Figure 5: REM sleep without atonia in a patient with REM sleep behaviour disorder.

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References

  1. National Commission on Sleep Disorders Research. Report of the National Commission on Sleep Disorders Research (Research DHHS Pub. No. 92. Supplier of Documents, U. S. Government Printing Office, Washington, DC, 1992).

  2. Caples, S. M., Gami, A. S. & Somers, V. K. Obstructive sleep apnea. Ann. Intern. Med. 142, 187–197 (2005).

    Article  Google Scholar 

  3. Guillemiault, C. & Framherz, S. in Principles and Practice of Sleep Medicine (eds Kryger, M. H., Roth, T. & Dement, W. C.) 780–790 (Elsevier Saunders, Philadelphia, 2005).

    Book  Google Scholar 

  4. Nobili, L. et al. Ultradian aspects of sleep in narcolepsy. Neurophysiol. Clin. 26, 51–59 (1996).

    Article  CAS  Google Scholar 

  5. Bassetti, C. & Aldrich, M. S. Narcolepsy. Neurologic Clinics 14, 545–571 (1996).

    Article  CAS  Google Scholar 

  6. Mignot, E. Genetic and familial aspects of narcolepsy. Neurology 50 (suppl. 1), S16–S22 (1998).

    Article  CAS  Google Scholar 

  7. Taheri, S., Zeitzer, J. M. & Mignot, E. The role of hypocretins (orexins) in sleep regulation and narcolepsy. Annu. Rev. Neurosci. 25, 283–313 (2002).

    Article  CAS  Google Scholar 

  8. Mignot, E. et al. The role of cerebrospinal fluid hypocretin measurement in the diagnosis of narcolepsy and other hypersomnias. Arch. Neurol. 59, 1553–1562 (2002).

    Article  Google Scholar 

  9. Johns, J., Wu, M.- F. & Siegel, J. M. Systemic administration of hypocretin-1 reduces cataplexy and normalizes sleep and waking durations in narcoleptic dogs. Sleep Res. Online 3, 23–28 (2000).

    Google Scholar 

  10. Bonnet, M. H. & Arand, D. L. Activity, arousal, and the MSLT in patients with insomnia. Sleep 23, 205–212 (2000).

    Article  CAS  Google Scholar 

  11. Stepanski, E., Zorick, F., Roehrs, T., Young, D. & Roth, T. Daytime alertness in patients with chronic insomnia compared with asymptomatic control subjects. Sleep 11, 54–60 (1998).

    Article  Google Scholar 

  12. Vgontzas, A. N. et al. Chronic insomnia is associated with nyctohemeral activation of the hypothalamic-pituitary-adrenal axis: clinical implications. J. Endocrinol. Metab. 86, 3787–3794 (2001).

    Article  CAS  Google Scholar 

  13. Perlis, M. L., Merica, H., Smith, M. T. & Giles, D. E. Beta EEG activity and insomnia. Sleep Med. Rev. 5, 365–376 (2001).

    Article  Google Scholar 

  14. Smith, M. T. et al. Neuroimaging of NREM sleep in primary insomnia: a Tc-99-HMPAO single photon emission computed tomographic study. Sleep 25, 325–335 (2002).

    Article  Google Scholar 

  15. Lasagna, L. Over-the-counter hypnotics and chronic insomnia in the elderly. J. Clin. Psychopharmacol. 15, 383–386 (1995).

    Article  CAS  Google Scholar 

  16. Mendelson, W. B. et al. The treatment of chronic insomnia: drug indications, chronic use and abuse liability. Summary of a 2001 new clinical drug evaluation unit meeting symposium. Sleep Med. Rev. 8, 7–17 (2004).

    Article  Google Scholar 

  17. Schenck, C. H. & Mahowald, M. W. Long-term, nightly benzodiazepine treatment of injurious parasomnias and other disorders of disrupted nocturnal sleep in 170 adults. Am. J. Med. 100, 333–337 (1996).

    Article  CAS  Google Scholar 

  18. Hajak, G., Bandelow, B., Zulley, J. & Pittrow, D. ‘As needed’ pharmacotherapy combined with stimulus control treatment in chronic insomnia — assessment of a novel interventional strategy in a primary care setting. Ann. Clin. Psychiatry 14, 1–7 (2002).

    Article  Google Scholar 

  19. Morin, C. M., Bastien, C. H., Brink, D. & Brown, T. R. Adverse effects of temazepam in older adults with chronic insomnia. Hum. Pschyopharmacol. Clin. Exper. 18, 75–82 (2003).

    Article  CAS  Google Scholar 

  20. Dawson, D. & van den Heuvel, C. J. Integrating the actions of melatonin on human physiology. Ann. Med. 30, 95–102 (1998).

    Article  CAS  Google Scholar 

  21. Phillips, B. et al. Epidemiology of restless legs symptoms in adults. Arch. Intern. Med. 160, 2137–2141 (2000).

    Article  CAS  Google Scholar 

  22. Trenkwalder, C. et al. Circadian rhythm of periodic limb movements and sensory symptoms of restless legs syndrome. Mov. Dis. 14, 102–110 (1999).

    Article  CAS  Google Scholar 

  23. Winkelman, J. et al. ‘Anxietas Tibiarum’. Depression and anxiety disorders in patients with restless legs syndrome. J. Neurol. 252, 67–71 (2005).

    Article  Google Scholar 

  24. Desautels, A. et al. Restless legs syndrome. Confirmation of linkage to chromosome 12q, genetic heterogeneity, and evidence of complexity. Arch. Neurol. 62, 591–596 (2005).

    Article  Google Scholar 

  25. Allen, R. P. & Earley, C. J. Restless legs syndrome: a review of clinical and pathophysiologic features. J. Clin. Neurophysiol. 18, 128–147 (2001).

    Article  CAS  Google Scholar 

  26. Bucher, S. F., Seelos, K. C., Oertel, W. H., Reiser, M. & Trenkwalder, C. Cerebral generators involved in the pathogenesis of the restless legs syndrome. Ann. Neurol. 41, 639–645 (1997).

    Article  CAS  Google Scholar 

  27. Turjanski, N., Lees, A. J. & Brooks, D. J. Striatal dopaminergic function in restless legs syndrome. Neurology 52, 932–937 (1999).

    Article  CAS  Google Scholar 

  28. Tergau, F., Wischer, S. & Paulus, W. Motor system excitability in patients with restless legs syndrome. Neurology 52, 1060–1063 (1999).

    Article  CAS  Google Scholar 

  29. Stiasny-Kolster, K., Magerl, W., Oertel, W. H., Moller, J. C. & Treede, R.- D. Static mechanical hyperalgesia without dynamic tactile allodynia in patients with restless legs syndrome. Brain 127, 773–782 (2004).

    Article  CAS  Google Scholar 

  30. von Spiczak, S. et al. The role of opioids in restless legs syndrome: an [11C]diprenorphine PET study. Brain 128, 906–917 (2005).

    Article  Google Scholar 

  31. Moore-Ede, M. C., Sulzman, F. M. & Fuller, C. A. The Clocks That Time Us: Physiology of the Circadian Timing System (Harvard Univ. Press, Cambridge, MA, 1982).

    Google Scholar 

  32. Sack, R. L., Lewy, A. J., Blood, M. L., Keith, L. D. & Nakagawa, H. Circadian rhythm abnormalities in totally blind people; incidence and clinical significance. J. Clin. Endocrinol. Metab. 75, 127–134 (1992).

    CAS  PubMed  Google Scholar 

  33. Sack, R. L., Lewy, A. J. & Hughes, R. J. Guidelines for prescribing melatonin for sleep and circadian rhythm disorders. Ann. Med. 30, 115–121 (1998).

    Article  CAS  Google Scholar 

  34. Czeisler, C. A., Richardson, G. S. & Coleman, R. M. Chronotherapy: resetting the circadian clocks of patients with delayed sleep phase insomnia. Sleep 4, 1–21 (1981).

    Article  CAS  Google Scholar 

  35. Reid, K. J. & Zee, P. C. in Principles and Practice of Sleep Medicine (eds Kryger, M. H., Roth, T. & Dement, W. C.) 691–701 (Elsevier Saunders, Philadelphia, 2005).

    Book  Google Scholar 

  36. Yamadera, H., Takahashi, K. & Okawa, M. A multicenter study of sleep-wake rhythm disorders: clinical features of sleep-wake rhythm disorders. Psychiatr. Clin. Neurosci. 50, 195–201 (1996).

    Article  CAS  Google Scholar 

  37. Xu, W. et al. Functional consequences of a CKI-delta mutation causing familial advanced sleep phase syndrome. Nature 434, 640–644 (2005).

    Article  ADS  CAS  Google Scholar 

  38. Toh, K. L. et al. An hPer2 phosphorylation site mutation in familial advanced sleep phase syndrome. Science 291, 1040–1043 (2001).

    Article  ADS  CAS  Google Scholar 

  39. Archer, S. N. et al. A length polymorphism in the circadian clock gene Per3 is linked to delayed sleep phase syndrome and extreme diurnal preference. Sleep 26, 413–415 (2003).

    Article  Google Scholar 

  40. Dagan, Y., Yovel, I., Hallis, D., Eisenstein, M. & Raichik, I. Evaluating the role of melatonin in the long-term treatment of delayed sleep phase syndrome (DSPS). Chronobiol. Inter. 15, 181–190 (1998).

    Article  CAS  Google Scholar 

  41. Mahowald, M. W. & Schenck, C. H. Evolving concepts of human state dissociation. Arch. Ital. Biol. 139, 269–300 (2001).

    CAS  PubMed  Google Scholar 

  42. Mahowald, M. W. & Schenck, C. H. in Principles and Practice of Sleep Medicine (eds. Kryger, M. H., Roth, T. & Dement, W. C.) 786–795 (W. B. Saunders, Philadelphia, 2000).

    Google Scholar 

  43. Fisher, C., Kahn, E., Edwards, A. & Davis, D. M. A psychophysiological study of nightmares and night terrors. I. Physiological aspects of the stage 4 night terror. J. Nerv. Ment. Dis. 157, 75–98 (1973).

    Article  CAS  Google Scholar 

  44. Fisher, C., Kahn, E., Edwards, A., Davis, D. M. & Fine, J. A psychophysiological study of nightmares and night terrors. III. Mental content and recall of stage 4 night terrors. J. Nerv. Ment. Dis. 158, 174–188 (1974).

    Article  CAS  Google Scholar 

  45. Schenck, C. H., Hurwitz, T. D., Bundlie, S. R. & Mahowald, M. W. Sleep-related injury in 100 adult patients: a polysomnographic and clinical report. Am. J. Psychiatr. 146, 1166–1173 (1989).

    Article  CAS  Google Scholar 

  46. Guilleminault, C., Moscovitch, A. & Leger, D. Forensic sleep medicine: nocturnal wandering and violence. Sleep 18, 740–748 (1995).

    Article  CAS  Google Scholar 

  47. Llorente, M. D., Currier, M. B., Norman, S. & Mellman, T. A. Night terrors in adults: phenomenology and relationship to psychopathology. J. Clin. Psychiatr. 53, 392–394 (1992).

    CAS  Google Scholar 

  48. Shapiro, C. M., Trajanovic, N. N. & Fedoroff, J. P. Sexsomnia — a new parasomnia? Can. J. Psychiatr. 48, 311–317 (2003).

    Article  Google Scholar 

  49. Winkelman, J. W., Herzog, D. B. & Fava, M. The prevalence of sleep-related eating disorder in psychiatric and non-psychiatric populations. Psychol. Med. 29, 1461–1466 (1999).

    Article  CAS  Google Scholar 

  50. Schenck, C. H. & Mahowald, M. W. Review of nocturnal sleep-related eating disorders. Int. J. Eat. Dis. 15, 343–356 (1994).

    Article  CAS  Google Scholar 

  51. Rosenfeld, D. S. & Elhajjar, A. J. Sleepsex: a variant of sleepwalking. Arch. Sex. Behav. 27, 269–278 (1998).

    Article  CAS  Google Scholar 

  52. Rosen, G., Mahowald, M. W. & Ferber, R. in Principles and Practice of Sleep Medicine in the Child (eds Ferber, R. & Kryger, M.) 99–106 (W. B. Saunders, Philadelphia, 1995).

    Google Scholar 

  53. Nino-Murcia, G. & Dement, W. C. in Psychopharmacology: the Third Generation of Progress (ed. Meltzer, H. Y.) 873–879 (Raven, New York, 1987).

    Google Scholar 

  54. Ohayon, M., Guilleminault, C. & Priest, R. G. Night terrors, sleepwalking, and confusional arousals in the general population: their frequency and relationship to other sleep and mental disorders. J. Clin. Psychiatr. 60, 268–276 (1999).

    Article  CAS  Google Scholar 

  55. Klackenberg, G. Somnambulism in childhood — prevalence, course and behavior correlates. A prospective longitudinal study (6-16 years). Acta Paediatr. Scan. 71, 495–499 (1982).

    Article  CAS  Google Scholar 

  56. Kahn, E., Fisher, C. & Edwards, A. in The Mind in Sleep. Psychology and Psychophysiology (eds Ellman, S. D. & Antrobus, J. S.) 437–447 (John Wiley & Sons, New York, 1991).

    Google Scholar 

  57. Mahowald, M. W. & Schenck, C. H. in Principles and Practice of Sleep Medicine (eds Kryger, M. H., Roth, T. & Dement, W. C.) 960–968 (Elsevier/Saunders, Philadelphia, 2005).

    Book  Google Scholar 

  58. Mahowald, M. W. & Cramer-Bornemann, M. A. in Principles and Practice of Sleep Medicine (eds Kryger, M. H., Roth, T. & Dement, W. C.) 889–896 (Elsevier/Saunders, Philadelphia, 2005).

    Book  Google Scholar 

  59. Schenck, C. H. in Encyclopedia of the Neurological Sciences (eds Aminoff, M. J. & Daroff, R. B.) 146–149 (Academic, San Diego, 2003).

    Book  Google Scholar 

  60. Mahowald, M. W. & Schenck, C. H. in Principles and Practice of Sleep Medicine (eds. Kryger, M. H., Roth, T. & Dement, W. C.) 897–916 (Elsevier/Saunders, Philadelphia, 2005).

    Book  Google Scholar 

  61. Boeve, B. F. et al. Synuceinopathy pathology often underlies REM sleep behavior disorder and dementia or parkinsonism. Neurology 61, 40–45 (2003).

    Article  CAS  Google Scholar 

  62. Eisensehr, I. et al. Reduced striatal dopamine transporters in idiopathic rapid eye movement sleep behavior disorder. Comparison with Parkinson's disease and controls. Brain 123, 1155–1160 (2000).

    Article  Google Scholar 

  63. Eisensehr, I. et al. Increased muscle activity during rapid eye movement sleep correlates with decrease of striatal presynaptic dopamine transporters. IPT and IBZM SPECT imaging in subclinical and clinically manifest idiopathic REM sleep behavior disorder, Parkinson's disease, and controls. Sleep 26, 507–512 (2003).

    Article  Google Scholar 

  64. Albin, R. L. et al. Decreased striatal dopaminergic innervation in REM sleep behavior disorder. Neurology 55, 1410–1412 (2000).

    Article  CAS  Google Scholar 

  65. Shirakawa, S.- I. et al. Study of image findings in rapid eye movement sleep behavioral disorder. Psychiatr. Clin. Neurosci. 56, 291–292 (2002).

    Article  Google Scholar 

  66. Fantini, M. L. et al. Slowing of electroencephalogram in rapid eye movement sleep behavior disorder. Ann. Neurol. 53, 774–780 (2003).

    Article  Google Scholar 

  67. Miyamoto, M. et al. Brainstem function in rapid eye movement sleep behavior disorder: the evaluation of brainstem function by proton MR spectroscopy (1H-MRS). Psychiatr. Clin. Neurosci. 54, 350–351 (2000).

    Article  CAS  Google Scholar 

  68. Gilman, S. et al. REM sleep behavior disorder is related to striatal monoaminergic deficit in MSA. Neurology 61, 29–34 (2003).

    Article  CAS  Google Scholar 

  69. Schenck, C. H. & Mahowald, M. W. Motor dyscontrol in narcolepsy: rapid-eye-movement (REM) sleep without atonia and REM sleep behavior disorder. Ann. Neurol. 32, 3–10 (1992).

    Article  CAS  Google Scholar 

  70. Schenck, C. H. & Mahowald, M. W. Polysomnographic, neurologic, psychiatric, and clinical outcome report on 70 consecutive cases with REM sleep behavior disorder (RBD): sustained clonazepam efficacy in 89.5% of 57 treated patients. Cleveland Clin. J. Med. 57 (Suppl.), S9–S23 (1990).

    Google Scholar 

  71. Petersen, A. et al. Orexin loss in Huntington's disease. Hum. Mol. Genet. 14, 39–47 (2005).

    Article  CAS  Google Scholar 

  72. Morton, A. J. et al. Disintegration of the sleep-wake cycle and circadian timing in Huntington's disease. J. Neurosci. 25, 1573–163 (2005).

    Article  Google Scholar 

  73. Wisor, J. P. et al. Sleep and circadian abnormalities in a transgenic mouse model of Alzheimer's disease: a role for cholinergic transmission. Neuroscience 131, 375–385 (2005).

    Article  CAS  Google Scholar 

  74. Dauvilliers, Y., Maret, S. & Tafti, M. Genetics of normal and pathological sleep. Sleep Med. Rev. 9, 91–100 (2005).

    Article  CAS  Google Scholar 

  75. Huber, R. et al. Sleep homeostasis in Drosophila melanogaster. Sleep 27, 628–639 (2004).

    Article  Google Scholar 

  76. Hendricks, J. C. & Sehgal, A. Why a fly? Using Drosophila to understand the genetics of circadian rhythms and sleep. Sleep 27, 334–342 (2004).

    Article  Google Scholar 

  77. Cirelli, C. et al. Reduced sleep in Drosophila Shaker mutants. Nature 434, 1087–1092 (2005).

    Article  ADS  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Neurology (MWM) and Psychiatry (CHS) Hennepin County Medical Center, Minnesota Regional Sleep Disorders Center, and University of MN Medical School, Minneapolis, 55415, Minnesota, USA

    Mark W. Mahowald & Carlos H. Schenck

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Correspondence to Mark W. Mahowald.

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The authors declare competing financial interests: Mark W. Mahowald - Research/Grant Support: Takeda, Cephalon, Lorex, Neurocrine, GalaxoKlineSmith, Pharmacia, Pfizer, Boehringer Ingelham, Aventis .

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Abnormal REM sleep behaviours documented in older men with 'REM sleep behaviour disorder'during sleep laboratory video-polysomnographic monitoring at the Minnesota Regional Sleep Disorders Center. (MPG 5362 kb)

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Mahowald, M., Schenck, C. Insights from studying human sleep disorders. Nature 437, 1279–1285 (2005). https://doi.org/10.1038/nature04287

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