Skip to main content

Advertisement

SpringerLink
Log in

Is Idiopathic Hypersomnia a Circadian Rhythm Disorder?

  • Hypersomnia Disorders (D Plante, Section Editor)
  • Published:
Current Sleep Medicine Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

The pathophysiology of idiopathic hypersomnia remains unclear, but some of its clinical features suggest the possibility of circadian dysfunction. This review will provide an overview of recent studies of circadian biology that have begun to elucidate the potential role of circadian rhythm dysfunction in idiopathic hypersomnia.

Recent Findings

Clinically, people with idiopathic hypersomnia tend to have both a late chronotype and prominent sleep inertia or sleep drunkenness. Melatonin and cortisol profiles in people with IH confirm this tendency toward phase delay. More recently, it has been suggested that the night phase as defined by melatonin profile or period length as defined by BMA1 in dermal fibroblasts may also be prolonged in people with IH. Additionally, amplitude of melatonin rhythm and circadian gene expression, particularly BMAL1, PER1, and PER2, may be impaired in this disease.

Summary

Clinical features, melatonin profiles, and circadian gene expression all suggest that abnormalities of the circadian system may be a contributor to the pathogenesis of IH.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. International classification of sleep disorders. 3rd ed. Darien, IL: American Acad. of Sleep Medicine.

  2. Billiard M, Sonka K. Idiopathic hypersomnia. Sleep Med Rev. 2016;29:23–33. https://doi.org/10.1016/j.smrv.2015.08.007.

    Article  PubMed  Google Scholar 

  3. Rye DB, Bliwise DL, Parker K, Trotti LM, Saini P, Fairley J, et al. Modulation of vigilance in the primary hypersomnias by endogenous enhancement of GABAA receptors. Sci Transl Med. 2012;4(161):161ra51. https://doi.org/10.1126/scitranslmed.3004685.

    Article  CAS  Google Scholar 

  4. Sforza E, Roche F, Barthelemy JC, Pichot V. Diurnal and nocturnal cardiovascular variability and heart rate arousal response in idiopathic hypersomnia. Sleep Med. 2016;24:131–6. https://doi.org/10.1016/j.sleep.2016.07.012.

    Article  PubMed  Google Scholar 

  5. Boucetta S, Montplaisir J, Zadra A, Lachapelle F, Soucy JP, Gravel P, et al. Altered regional cerebral blood flow in idiopathic hypersomnia. Sleep. 2017;40(10). https://doi.org/10.1093/sleep/zsx140.

  6. Dauvilliers Y, Evangelista E, de Verbizier D, Barateau L, Peigneux P. [18F]Fludeoxyglucose-positron emission tomography evidence for cerebral hypermetabolism in the awake state in narcolepsy and idiopathic hypersomnia. Front Neurol. 2017;8:–350. https://doi.org/10.3389/fneur.2017.00350.

  7. Silver R, Kriegsfeld LJ. Circadian rhythms have broad implications for understanding brain and behavior. Eur J Neurosci. 2014;39(11):1866–80. https://doi.org/10.1111/ejn.12593.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Czeisler CA, Duffy JF, Shanahan TL, Brown EN, Mitchell JF, Rimmer DW, et al. Stability, precision, and near-24-hour period of the human circadian pacemaker. Science. 1999;284(5423):2177–81.

    Article  CAS  Google Scholar 

  9. Fonken LK, Nelson RJ. The effects of light at night on circadian clocks and metabolism. Endocr Rev. 2014;35(4):648–70. https://doi.org/10.1210/er.2013-1051.

    Article  CAS  PubMed  Google Scholar 

  10. Mohawk JA, Green CB, Takahashi JS. Central and peripheral circadian clocks in mammals. Annu Rev Neurosci. 2012;35:445–62. https://doi.org/10.1146/annurev-neuro-060909-153128.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Pandi-Perumal SR, Smits M, Spence W, Srinivasan V, Cardinali DP, Lowe AD, et al. Dim light melatonin onset (DLMO): a tool for the analysis of circadian phase in human sleep and chronobiological disorders. Prog Neuro-Psychopharmacol Biol Psychiatry. 2007;31(1):1–11. https://doi.org/10.1016/j.pnpbp.2006.06.020.

    Article  CAS  Google Scholar 

  12. Roth B. Narcolepsy and hypersomnia: review and classification of 642 personally observed cases. Schweiz Arch Neurol Neurochir Psychiatr. 1976;119(1):31–41.

    CAS  PubMed  Google Scholar 

  13. Aldrich MS. The clinical spectrum of narcolepsy and idiopathic hypersomnia. Neurology. 1996;46(2):393–401. https://doi.org/10.1212/wnl.46.2.393.

    Article  CAS  PubMed  Google Scholar 

  14. Billiard M, Merle C, Carlander B, Ondze B, Alvarez D, Besset A. Idiopathic hypersomnia. Psychiatry Clin Neurosci. 1998;52(2):125–9. https://doi.org/10.1111/j.1440-1819.1998.tb00987.x.

    Article  CAS  PubMed  Google Scholar 

  15. Bassetti C, Aldrich MS. Idiopathic hypersomnia. A series of 42 patients. Brain. 1997;120(Pt 8):1423–35. https://doi.org/10.1093/brain/120.8.1423.

    Article  PubMed  Google Scholar 

  16. Komada Y, Inoue Y, Mukai J, Shirakawa S, Takahashi K, Honda Y. Difference in the characteristics of subjective and objective sleepiness between narcolepsy and essential hypersomnia. Psychiatry Clin Neurosci. 2005;59(2):194–9. https://doi.org/10.1111/j.1440-1819.2005.01357.x.

    Article  PubMed  Google Scholar 

  17. Anderson KN, Pilsworth S, Sharples LD, Smith IE, Shneerson JM. Idiopathic hypersomnia: a study of 77 cases. Sleep. 2007;30(10):1274–81. https://doi.org/10.1093/sleep/30.10.1274.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Sonka K, Susta M, Billiard M. Narcolepsy with and without cataplexy, idiopathic hypersomnia with and without long sleep time: a cluster analysis. Sleep Med. 2015;16(2):225–31. https://doi.org/10.1016/j.sleep.2014.09.016.

    Article  PubMed  Google Scholar 

  19. Ali M, Auger RR, Slocumb NL, Morgenthaler TI. Idiopathic hypersomnia: clinical features and response to treatment. J Clin Sleep Med. 2009;5(6):562–8.

    PubMed  PubMed Central  Google Scholar 

  20. • Vernet C, Leu-Semenescu S, Buzare MA, Arnulf I. Subjective symptoms in idiopathic hypersomnia: beyond excessive sleepiness. J Sleep Res. 2010;19(4):525–34. https://doi.org/10.1111/j.1365-2869.2010.00824.xThis controlled cohort study reports subjective symptoms of idiopathic hypersomnia patients including the frequency of sleep drunkenness and chronotype HO scores.

    Article  PubMed  Google Scholar 

  21. • Vernet C, Arnulf I. Idiopathic hypersomnia with and without long sleep time: a controlled series of 75 patients. Sleep. 2009;32(6):753–9. https://doi.org/10.1093/sleep/32.6.753This controlled prospective cohort study compares symptoms of IH patients with those of healthy controls including HO scores.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Lane JM, Vlasac I, Anderson SG, Kyle SD, Dixon WG, Bechtold DA, et al. Genome-wide association analysis identifies novel loci for chronotype in 100,420 individuals from the UK biobank. Nat Commun. 2016;7:10889. https://doi.org/10.1038/ncomms10889.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Jones SE, Tyrrell J, Wood AR, Beaumont RN, Ruth KS, Tuke MA, et al. Genome-wide association analyses in 128,266 individuals identifies new Morningness and sleep duration loci. PLoS Genet. 2016;12(8):e1006125. https://doi.org/10.1371/journal.pgen.1006125.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Hu Y, Shmygelska A, Tran D, Eriksson N, Tung JY, Hinds DA. GWAS of 89,283 individuals identifies genetic variants associated with self-reporting of being a morning person. Nat Commun. 2016;7:10448. https://doi.org/10.1038/ncomms10448.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Horne JA, Ostberg O. A self-assessment questionnaire to determine morningness-eveningness in human circadian rhythms. Int J Chronobiol. 1976;4(2):97–110.

    CAS  PubMed  Google Scholar 

  26. •• Materna L, Halfter H, Heidbreder A, Boentert M, Lippert J, Koch R, et al. Idiopathic hypersomnia patients revealed longer circadian period length in peripheral skin fibroblasts. Front Neurol. 2018;9:424. https://doi.org/10.3389/fneur.2018.00424This study investigates the circadian period length in IH patients compared to healthy controls by using peripheral circadian clock cells.

    Article  PubMed  PubMed Central  Google Scholar 

  27. •• Trotti LM. Waking up is the hardest thing I do all day: sleep inertia and sleep drunkenness. Sleep Med Rev. 2017;35:76-84. Doi:https://doi.org/10.1016/j.smrv.2016.08.005. This review article reports alleviating and aggravating factors of both sleep inertia and sleep drunkenness.

    Article  Google Scholar 

  28. Scheer FA, Shea TJ, Hilton MF, Shea SA. An endogenous circadian rhythm in sleep inertia results in greatest cognitive impairment upon awakening during the biological night. J Biol Rhythm. 2008;23(4):353–61. https://doi.org/10.1177/0748730408318081.

    Article  Google Scholar 

  29. •• Nevsimalova S, Blazejova K, Illnerova H, Hajek I, Vankova J, Pretl M, et al. A contribution to pathophysiology of idiopathic hypersomnia. Suppl Clin Neurophysiol. 2000;53:366–70 This controlled cohort study provides evidence of delayed circadian phases in IH patients by examining salivary melatonin and cortisol levels.

    Article  CAS  Google Scholar 

  30. Nowak R, McMillen IC, Redman J, Short RV. The correlation between serum and salivary melatonin concentrations and urinary 6-hydroxymelatonin sulphate excretion rates: two non-invasive techniques for monitoring human circadian rhythmicity. Clin Endocrinol. 1987;27(4):445–52.

    Article  CAS  Google Scholar 

  31. Thomas R, Naik S. The circadian variant of idiopathic hypersomnia. Sleep. 2017;40(1):a243.

    Article  Google Scholar 

  32. Janackova S, Motte J, Bakchine S, Sforza E. Idiopathic hypersomnia: a report of three adolescent-onset cases in a two-generation family. J Child Neurol. 2011;26(4):522–5. https://doi.org/10.1177/0883073810384865.

    Article  PubMed  Google Scholar 

  33. Nevsimalova-Bruhova S, Roth B. Heredofamilial aspects of narcolepsy and hypersomnia. Schweiz Arch Neurol Neurochir Psychiatr. 1972;110(1):45–54.

    CAS  PubMed  Google Scholar 

  34. Billiard M, Dauvilliers Y. Idiopathic hypersomnia. Sleep Med Rev. 2001;5(5):349–58. https://doi.org/10.1053/smrv.2001.0168.

    Article  CAS  PubMed  Google Scholar 

  35. • Schirmacher AHH, Heidbreder A, Happe S, Kelsch R, Kuhlenbäumer G, Mayer G, et al. Sequence variants in circadian rhythmic genes in a cohort of patients suffering from hypersomnia of central origin. Biol Rhythm Res. 2011;42(5):407–16. https://doi.org/10.1080/09291016.2010.525382This candidate-gene associations study examines polymorphisms of circadian rhythmic genes in patients with EDS.

    Article  Google Scholar 

  36. •• Lippert J, Halfter H, Heidbreder A, Rohr D, Gess B, Boentert M, et al. Altered dynamics in the circadian oscillation of clock genes in dermal fibroblasts of patients suffering from idiopathic hypersomnia. PLoS One. 2014;9(1):e85255. https://doi.org/10.1371/journal.pone.0085255This cohort control study provides evidence of impaired gene expression of peripheral circadian clock genes in IH patients.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Moller-Levet CS, Archer SN, Bucca G, Laing EE, Slak A, Kabiljo R, et al. Effects of insufficient sleep on circadian rhythmicity and expression amplitude of the human blood transcriptome. Proc Natl Acad Sci U S A. 2013;110(12):E1132–41. https://doi.org/10.1073/pnas.1217154110.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This was supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under Award Number K23 NS083748. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Author information

Authors and Affiliations

  1. Emory Sleep Center and Department of Neurology, Emory University School of Medicine, 12 Executive Park Dr NE, Atlanta, GA, 30329, USA

    David Landzberg & Lynn Marie Trotti

Authors
  1. David Landzberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lynn Marie Trotti
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lynn Marie Trotti.

Ethics declarations

Conflict of Interest

Dr. Trotti reports fees to her institution from Jazz Pharmaceuticals, Balance Therapeutics, and Harmony Biosciences, outside this work. There are no financial or other conflicts of interest related to this article.

Human and Animal Rights Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

All authors stated have viewed and approved this manuscript

This article is part of the Topical Collection on Hypersomnia Disorders

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Landzberg, D., Trotti, L.M. Is Idiopathic Hypersomnia a Circadian Rhythm Disorder?. Curr Sleep Medicine Rep 5, 201–206 (2019). https://doi.org/10.1007/s40675-019-00154-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40675-019-00154-x

Keywords

Search

Navigation