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Non-24-Hour Sleep-Wake Rhythm Disorder

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Circadian Rhythm Sleep-Wake Disorders

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Abstract

Non-24-hour sleep/wake rhythm disorder (non-24) most commonly presents in totally blind individuals and results from the loss of synchronization (entrainment) of the hypothalamic circadian pacemaker to the 24-hour day. The etiology of the disorder in the sighted is likely distinct from that in the blind and has yet to be definitively demonstrated. Diagnosis of this disorder is based on the patient’s report of relapsing and remitting symptoms of daytime hypersomnolence and/or nighttime insomnia as well as sleep/wake timing that can drift progressively later or earlier each day as documented by sleep diaries or wrist actigraphy. Both melatonin and the melatonin agonist tasimelteon have been shown to successfully entrain the circadian pacemaker in placebo-controlled trials and thereby treat the disorder. The clinician must carefully consider both the time and dose of melatonin administration to achieve the optimal clinical result. Controlled trials of light or melatonin are lacking in the treatment of non-24 among the sighted, but the use of both may be effective when the patients’ self-selected light/dark schedules are taken into account.

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References

  1. Medicine AAoS. International classification of sleep disorders. American Academy of Sleep Medicine: Darien; 2014.

    Google Scholar 

  2. Lucas RJ, Lall GS, Allen AE, Brown TM. How rod, cone, and melanopsin photoreceptors come together to enlighten the mammalian circadian clock. Prog Brain Res. 2012;199:1–18.

    Article  CAS  PubMed  Google Scholar 

  3. Czeisler CA, Kronauer RE, Allan JS, et al. Bright light induction of strong (Type O) resetting of the human circadian pacemaker. Science. 1989;244:1328–33.

    Article  CAS  PubMed  Google Scholar 

  4. Khalsa SB, Jewett ME, Cajochen C, Czeisler CA. A phase-response curve to single bright light pulses in human subjects. J Physiol. 2003;549:945–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. St Hilaire MA, Gooley JJ, Khalsa SB, Kronauer RE, Czeisler CA, Lockley SW. Human phase response curve to a 1h pulse of bright white light. J Physiol. 2012;590:3035–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Duffy JF, Cain SW, Chang AM, et al. Sex difference in the near-24-hour intrinsic period of the human circadian timing system. Proc Natl Acad Sci U S A. 2011;108:15602–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Czeisler CA, Duffy JF, Shanahan TL, et al. Stability, precision and near-24-hour period of the human circadian pacemaker. Science. 1999;284:2177–81.

    Article  CAS  PubMed  Google Scholar 

  8. Lewy AJ, Sack RL. The dim light melatonin onset as a marker for circadian phase position. Chronobiol Int. 1989;6:93–102.

    Article  CAS  PubMed  Google Scholar 

  9. Lewy AJ, Cutler NL, Sack RL. The endogenous melatonin profile as a marker for circadian phase position. J Biol Rhythm. 1999;14:227–36.

    Article  CAS  Google Scholar 

  10. Klerman EB, Gershengorn HB, Duffy JF, Kronauer RE. Comparisons of the variability of three markers of the human circadian pacemaker. J Biol Rhythm. 2002;17:181–93.

    Article  CAS  PubMed  Google Scholar 

  11. Martin SK, Eastman CI. Sleep logs of young adults with self-selected sleep times predict the dim light melatonin onset. Chronobiol Int. 2002;19:695–707.

    Article  PubMed  Google Scholar 

  12. Burgess HJ, Eastman CI. The dim light melatonin onset following fixed and free sleep schedules. J Sleep Res. 2005;14:229–37.

    Article  PubMed  Google Scholar 

  13. Burgess HJ, Fogg LF. Individual differences in the amount and timing of salivary melatonin secretion. PLoS One. 2008;3:e3055.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Emens JS, Yuhas K, Rough J, Kochar N, Peters D, Lewy AJ. Phase angle of entrainment in morning- and evening-types under naturalistic conditions. Chronobiol Int. 2009;26:474–93.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Emens JS, Laurie AL, Songer JB, Lewy AJ. Non-24-hour disorder in blind individuals revisited: variability and the influence of environmental time cues. Sleep. 2013;36:1091–100.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Lockley SW, Skene DJ, Arendt J, Tabandeh H, Bird AC, Defrance R. Relationship between melatonin rhythms and visual loss in the blind. J Clin Endocrinol Metab. 1997;82:3763–70.

    CAS  PubMed  Google Scholar 

  17. Czeisler CA, Shanahan TL, Klerman EB, et al. Suppression of melatonin secretion in some blind patients by exposure to bright light. New Engl J Med. 1995;332:6–11.

    Article  CAS  PubMed  Google Scholar 

  18. Klerman EB, ShanahanTL, Brotman DJ, et al. Photic resetting of the human circadian pacemaker in the absence of conscious vision. J Biol Rhythm. 2002;17:548–55.

    Article  CAS  PubMed  Google Scholar 

  19. LeGates TA, Fernandez DC, Hattar S. Light as a central modulator of circadian rhythms, sleep and affect. Nat Rev Neurosci. 2014;15:443–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Emens JS, Brotman DJ, Czeisler CA. Evaluation of the intrinsic period of the circadian pacemaker in a patient with a non-24-hour sleep-wake schedule disorder. Sleep Res. 1994;23:256.

    Google Scholar 

  21. Uchiyama M, Lockley SW. Non-24-hour sleep-wake syndreom in sighted and blind patients. Sleep Med Clin. 2009;4:195–211.

    Article  Google Scholar 

  22. Hayakawa T, Uchiyama M, Kamei Y, et al. Clinical analyses of sighted patients with non-24-hour sleep-wake syndrome: a study of 57 consecutively diagnosed cases. Sleep. 2005;28:945–52.

    Article  PubMed  Google Scholar 

  23. Kitamura S, Hida A, Enomoto M, et al. Intrinsic circadian period of sighted patients with circadian rhythm sleep disorder, free-running type. Biol Psychiatry. 2013;73:63–9.

    Article  PubMed  Google Scholar 

  24. Wever R. The circadian system of man: results of experiments under temporal isolation. New York, NY: Springer-Verlag; 1979.

    Book  Google Scholar 

  25. Czeisler CA, Weitzman ED, Moore-Ede MC, Zimmerman JC, Knauer RS. Human sleep: its duration and organization depend on its circadian phase. Science. 1980;210:1264–9.

    Article  CAS  PubMed  Google Scholar 

  26. Wittmann M, Dinich J, Merrow M, Roenneberg T. Social jetlag: misalignment of biological and social time. Chronobiol Int. 2006;23:497–509.

    Article  PubMed  Google Scholar 

  27. Stothard ER, McHill AW, Depner CM, et al. Circadian entrainment to the natural light-dark cycle across seasons and the weekend. Curr Biol. 2017;27:508–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Czeisler CA, Richardson GS, Coleman RM, et al. Chronotherapy: resetting the circadian clocks of patients with delayed sleep phase insomnia. Sleep. 1981;4:1–21.

    Article  CAS  PubMed  Google Scholar 

  29. Sack RL, Lewy AJ, Blood ML, Keith LD, Nakagawa H. Circadian rhythm abnormalities in totally blind people: incidence and clinical significance. J Clin Endocrinol Metab. 1992;75:127–34.

    CAS  PubMed  Google Scholar 

  30. Lockley SW, Dressman MA, Licamele L, et al. Tasimelteon for non-24-hour sleep–wake disorder in totally blind people (SET and RESET): two multicentre, randomised, double-masked, placebo-controlled phase 3 trials. Lancet. 2015;386:1754–64.

    Article  CAS  PubMed  Google Scholar 

  31. Lockley SW, Skene DJ, Butler LJ, Arendt J. Sleep and activity rhythms are related to circadian phase in the blind. Sleep. 1999;22:616–23.

    Article  CAS  PubMed  Google Scholar 

  32. Sack RL, Lewy AJ, Blood ML, Keith LD, Nakagawa H. Circadian rhythm abnormalities in totally blind people: incidence and clinical significance. J Clin Endocrinol Metab. 1992;75:127–34.

    CAS  PubMed  Google Scholar 

  33. Burgess HJ, Wyatt JK, Park M, Fogg LF. Home circadian phase assessments with measures of compliance yield accurate dim light melatonin onsets. Sleep. 2015;38:889–97.

    PubMed  PubMed Central  Google Scholar 

  34. Sack RL, Brandes RW, Kendall AR, Lewy AJ. Entrainment of free-running circadian rhythms by melatonin in blind people. New Engl J Med. 2000;343:1070–7.

    Article  CAS  PubMed  Google Scholar 

  35. Leger D, Guilleminault C, Defrance R, Domont A, Paillard M. Prevalence of sleep/wake disorders in persons with blindness. Clin Sci (Lond). 1999;97:193–9.

    Article  CAS  Google Scholar 

  36. Scheer FAJL, Hilton MF, Mantzoros CS, Shea SA. Adverse metabolic and cardiovascular consequences of circadian misalignment. Proc Natl Acad Sci U S A. 2009;106:4453–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Ruger M, Scheer FAJL. Effects of circadian disruption on the cardiometabolic system. Rev Endocr Metab Disord. 2009;10:245.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Vogel M, Braungardt T, Meyer W, Schneider W. The effects of shift work on physical and mental health. J Neural Trans. 2012;119:1121–32.

    Article  Google Scholar 

  39. Jagannath A, Peirson SN, Foster RG. Sleep and circadian rhythm disruption in neuropsychiatric illness. Curr Opin Neurobiol. 2013;23:888–94.

    Article  CAS  PubMed  Google Scholar 

  40. Kelleher FC, Rao A, Maguire A. Circadian molecular clocks and cancer. Cancer Lett. 2014;342:9–18.

    Article  CAS  PubMed  Google Scholar 

  41. Lewy AJ, Bauer VK, Ahmed S, et al. The human phase response curve (PRC) to melatonin is about 12 hours out of phase with the PRC to light. Chronobiol Int. 1998;15:71–83.

    Article  CAS  PubMed  Google Scholar 

  42. Burgess HJ, Revell VL, Molina TA, Eastman CI. Human phase response curves to three days of daily melatonin: 0.5 mg versus 3.0 mg. J Clin Endocrinol Metab. 2010;95:3325–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Lockley SW, Skene DJ, James K, Thapan K, Wright J, Arendt J. Melatonin administration can entrain the free-running circadian system of blind subjects. J Endocrinol. 2000;164:R1–6.

    Article  CAS  PubMed  Google Scholar 

  44. Hack LM, Lockley SW, Arendt J, Skene DJ. The effects of low-dose 0.5-mg melatonin on the free-running circadian rhythms of blind subjects. J Biol Rhythm. 2003;18:420–9.

    Article  CAS  Google Scholar 

  45. Lewy AJ, Bauer VK, Hasler BP, Kendall AR, Pires ML, Sack RL. Capturing the circadian rhythms of free-running blind people with 0.5 mg melatonin. Brain Res. 2001;918:96–100.

    Article  CAS  PubMed  Google Scholar 

  46. Lewy AJ, Hasler BP, Emens JS, Sack RL. Pretreatment circadian period in free-running blind people may predict the phase angle of entrainment to melatonin. Neurosci Lett. 2001;313:158–60.

    Article  CAS  PubMed  Google Scholar 

  47. Lewy AJ, Emens JS, Sack RL, Hasler BP, Bernert RA. Low, but not high, doses of melatonin entrained a free-running blind person with a long circadian period. Chronobiol Int. 2002;19:649–58.

    Article  CAS  PubMed  Google Scholar 

  48. Lewy AJ, Emens JS, Bernert RA, Lefler BJ. Eventual entrainment of the human circadian pacemaker by melatonin is independent of the circadian phase of treatment initiation: clinical implications. J Biol Rhythm. 2004;19:68–75.

    Article  CAS  Google Scholar 

  49. Lewy AJ, Emens JS, Lefler BJ, Yuhas K, Jackman AR. Melatonin entrains free-running blind people according to a physiological dose-response curve. Chronobiol Int. 2005;22:1093–106.

    Article  CAS  PubMed  Google Scholar 

  50. Auger RR, Burgess HJ, Emens JS, Deriy LV, Thomas SM, Sharkey KM. Clinical practice guideline for the treatment of intrinsic circadian rhythm sleep-wake disorders: advanced sleep-wake phase disorder (ASWPD), delayed sleep-wake phase disorder (DSWPD), non-24-hour sleep-wake rhythm disorder (N24SWD), and irregular sleep-wake rhythm disorder (ISWRD). An update for 2015. J Clin Sleep Med. 2015;11:1199–236.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Emens J, Lewy AJ, Yuhas K, Jackman AR, Johnson KP. Melatonin entrains free-running blind individuals with circadian periods less than 24 hours. Sleep. 2006;29:A62.

    Google Scholar 

  52. Eastman CI, Anagnopoulus CA, Cartwright RD. Can bright light entrain a free-runner? Sleep Res. 1988;17:372.

    Google Scholar 

  53. Hoban TM, Sack RL, Lewy AJ, Miller LS, Singer CM. Entrainment of a free-running human with bright light? Chronobiol Int. 1989;6:347–53.

    Article  CAS  PubMed  Google Scholar 

  54. Hayakawa T, Kamei Y, Urata J, et al. Trials of bright light exposure and melatonin administration in a patient with non-24 hour sleep-wake syndrome. Psychiatry Clin Neurosci. 1998;52:261–2.

    Article  CAS  PubMed  Google Scholar 

  55. Watanabe T, Kajimura N, Kato M, Sekimoto M, Hori T, Takahashi K. Case of a non-24 h sleep-wake syndrome patient improved by phototherapy. Psychiatry Clin Neurosci. 2000;54:369–70.

    Article  CAS  PubMed  Google Scholar 

  56. McArthur AJ, Lewy AJ, Sack RL. Non-24-hour sleep-wake syndrome in a sighted man: circadian rhythm studies and efficacy of melatonin treatment. Sleep. 1996;19:544–53.

    Article  CAS  PubMed  Google Scholar 

  57. Kamei Y, Hayakawa T, Jujiro U, et al. Melatonin treatment for circadian rhythm sleep disorders. Psychiatry Clin Neurosci. 2000;54:381–2.

    Article  CAS  PubMed  Google Scholar 

  58. Watanabe A, Hirose M, Arakawa C, Iwata N, Kitajima T. A case of non-24-hour sleep-wake rhythm disorder treated with a low dose of ramelteon and behavioral education. J Clin Sleep Med. 2018;14:1265–7.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Zeitzer JM, Dijk DJ, Kronauer RE, Brown EN, Czeisler CA. Sensitivity of the human circadian pacemaker to nocturnal light: melatonin phase resetting and suppression. J Physiol. 2000;526:695–702.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Chang AM, Scheer FAJL, Czeisler CA. The human circadian system adapts to prior photic history. J Physiol. 2011;589:1095–102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Czeisler CA, Boivin DB, Duffey JF, Kronauer RE. Dose-response relationships for resetting of human circadian clock by light. Nature. 1996;379:540–1.

    Article  PubMed  Google Scholar 

  62. Gronfier C, Wright KP Jr, Kronauer RE, Jewett ME, Czeisler CA. Efficacy of a single sequence of intermittent bright light pulses for delaying circadian phase in humans. Am J Physiol Endocrinol Metab. 2004;287:E174–81.

    Article  CAS  PubMed  Google Scholar 

  63. Najjar RP, Zeitzer JM. Temporal integration of light flashes by the human circadian system. The J Clin Invest. 2016;126:938–47.

    Article  PubMed  Google Scholar 

  64. Rahman SA, St Hilaire MA, Chang AM, et al. Circadian phase resetting by a single short-duration light exposure. JCI Insight. 2017;2:e89494.

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Psychiatry, Oregon Health and Science University, Division of Mental Health and Clinical Neurosciences, VA Portland Health Care System, Portland, OR, USA

    Jonathan Emens

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  1. Jonathan Emens
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Correspondence to Jonathan Emens .

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  1. Mayo Center for Sleep Medicine, Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, Rochester, MN, USA

    R. Robert Auger

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Emens, J. (2020). Non-24-Hour Sleep-Wake Rhythm Disorder. In: Auger, R. (eds) Circadian Rhythm Sleep-Wake Disorders. Springer, Cham. https://doi.org/10.1007/978-3-030-43803-6_9

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  • DOI: https://doi.org/10.1007/978-3-030-43803-6_9

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