People who are totally blind are prone to a cyclic form of insomnia, designated in medical terminology as non-24-hour sleep-wake syndrome. It is caused by a lack of synchrony between the internal body clock and the daily sleep-wake schedule. This article describes the clinical features and biological basis of the disorder and discusses the implications for its management and treatment.
Get full access to this article
View all access options for this article.
References
1.
AmirS. & StewartJ. (1996). Resetting of the circadian clock by a conditioned stimulus. Nature, 379, 542–343
2.
ArendtJ. (1995). Melatonin and the mammalian pineal gland.London: Chapman & Hall.
3.
ArendtJ., AldhousM., & WrightJ. (1988). Synchronisation of a disturbed sleep-wake cycle in a blind man by melatonin treatment. Lancet, 1, 772–773.
4.
ArendtJ., SkeneD.J., MiddletonB., LockleyS.W., & DeaconS. (1997). Efficacy of melatonin treatment in jet lag, shift work, and blindness. Journal of Biological Rhythms, 12, 604–617.
5.
AschoffJ., FatranskaM., GereckeU., DrewwP., StammD., & WisserH. (1971). Human circadian rhythms in continuous darkness: Entrainment by social cues. Science, 171, 213–215.
6.
BodenheimerS., WinterJ.S.D., & FaimanC. (1973). Diurnal rhythms of serum gonadotropins, testosterone, estradiol and Cortisol in blind men. Journal of Clinical Endocrinology and Metabolism, 37, 472–475.
7.
BuxtonO.M., L'Hermite-BalèriauxM., HirschfeldV., & Van CauterE. (1997). Acute and delayed effects of exercise on human melatonin secretion. Journal of Biological Rhythms, 12, 568–574.
8.
CagnacciA., ElliottJ.A., & YenS.S.C. (1992). Melatonin: A major regulator of the circadian rhythm of core temperature in humans. Journal of Clinical Endocrinology and Metabolism, 75, 447–452.
9.
CzeislerC.A., RichardsonG.S., ZimmermanJ.C., Moore-EdeM.C., & WeitzmanE.D. (1981). Entrainment of human circadian rhythms by light-dark cycles: A reassessment. Photochemistry and Photobiology, 34, 239–247.
10.
CzeislerC.A., ShanahanT.L., KlermanE.B., MartensH., BrotmanD.J., EmansJ.S., KleinT., & RizzoJ.F. (1995). Suppression of melatonin secretion in some blind patients by exposure to bright light. New England Journal of Medicine, 332, 6–11.
11.
D'AlessandroB., BellastellaA., EspositoV., ColucciC.F., & MontalbettiN. (1974). Circadian rhythm of Cortisol secretion in elderly and blind subjects. British Medical Journal, 2, 274.
12.
DawsonD. & ArmstrongS. (1996). Chronobiotics—Drugs that shift rhythms. Pharmacology and Therapeutics, 69, 15–36.
13.
DijkD.J. & CzeislerC.A. (1995). Contribution of the circadian pacemaker and the sleep homeostat to sleep propensity, sleep structure, encephalographic slow waves, and sleep spindle activity in humans. Journal of Neuroscience, 15, 3326–3538.
14.
ElliottA.L., MillsJ.N., & WaterhouseJ.M. (1971). A man with too long a day. Journal of Physiology, 212, 30–31P.
15.
EspezelH., JanJ.E., O'DonnellM.E., & MilnerR. (1996). The use of melatonin to treat sleep-wake-rhythm disorders in children who are visually impaired. Journal of Visual Impairment & Blindness, 90, 43–50.
16.
FolkardS., ArendtJ., AldhousM., & KennettH. (1990). Melatonin stabilizes sleep onset time in a blind man without entrainment of Cortisol or temperature rhythms. Neuro-science Letters, 113, 193–198.
17.
HobanT.M., SackR.L., LewyA.J., & MillerL.S. (1989). Entrainment of a free-running human with bright light? Chronobiology International, 6, 347–353.
18.
HollwichF. & DieckhuesB. (1972). Circadian rhythm of Cortisol level in normal subjects and in the blind. Contemporary Opthalmology.Baltimore: Williams & Wilkins.
19.
HonmaK.I., HonmaS., NakamuraK., SasakiM., EndoT., & TakahashiT. (1995). Differential effects of bright light and social cues on reentrainment of human circadian rhythms. American Journal of Physiology, 268, R528–R535.
20.
HughesR.J. (1994). Melatonin, body temperature and sleep in humans: A review of a new hypnotic drug (Final report)Washington, DC: Air Force Office of Scientific Research, Boiling, Air Force Base.
21.
HughesR.J., BadiaP., FrenchJ., SantiagoL., & PlenzlerS. (1994). Melatonin induced changes in body temperature and daytime sleep. Sleep Research, 23, 496.
22.
JanJ.E., EspezelH., & AppletonR.E. (1994). The treatment of sleep disorders with melatonin. Developmental Medicine and Child Neurology, 36, 97–107.
23.
KleinD.C., MooreR.Y., & ReppertS.M. (Eds.). (1991). Suprachiasmatic nucleus: The Mind's Clock.New York: Oxford University Press.
24.
KriegerD.T. & GlickS. (1971). Absent sleep peak of growth hormone release in blind subjects; Correlation with sleep EEG stages. Journal of Clinical Endocrinology, 33, 847–850.
25.
LaitinenJ.T., CastrenE., VakkuriO., & SaavedraJ.M. (1989). Diurnal rhythm of melatonin binding in the rat suprachiasmatic nuclei. Endocrinology, 124, 1585–1587.
26.
LapierreO. & DumontM. (1995). Melatonin treatment of a non-24-hour sleep-wake cycle in a blind retarded child. Biological Psychiatry, 38, 119–122.
27.
LapierreO., DumontM., LesperanceP., & MontplaisirJ. (1993). Entrainment of a free-running sleep-wake cycle with melatonin in a blind retarded child. Sleep Research, 22, 627.
28.
LegerD., GuilleminaultC., & PaillardM. (1995). Epidemiology of sleep disorders in blind people. Sleep Research, 23, 527.
29.
LewyA.J. (1990). Chronobiologic disorders, social cues and the light-dark cycle. Chronobiology International, 7, 15–21.
30.
LewyA.J., AhmedS., JacksonJ.M.L., & SackR.L. (1992). Melatonin shifts circadian rhythms according to a phase-response curve. Chronobiology International, 9, 380–392.
31.
LewyA.J. & NewsomeD.A. (1983). Different types of melatonin circadian secretory rhythms in some blind subjects. Journal of Clinical Endocrinology and Metabolism, 56, 1103–1107.
32.
LewyA.J., SackR.L. & LathamJ. (1991). A phase response curve for melatonin administration in humans. Sleep Research, 20, 461.
McArthurA.J., LewyA.J., & SackR.L. (1996). Non-24-hour sleep-wake syndrome in a sighted man: Circadian rhythm studies and efficacy of melatonin treatment. Sleep, 19, 544–532.
35.
MigeonC.J., TylerF.H., MahoneyJ.P., FlorentinA.A., CastleH., BlissE.I., & SamuelsL.T. (1956). The diurnal variation of plasma levels and urinary excretion of 17-hydroxycorticosteroids in normal subjects, night workers and blind subjects. Journal of Clinical Endocrinology and Metabolism, 16, 622–633.
36.
MilesL.E.M., RaynalD.M., & WilsonM.A. (1977). Blind man living in normal society has circadian rhythms of 24.9 hours. Science, 198, 421–423.
37.
Moore-EdeM., SulzmanF.M., & FullerC.A. (1982). The clocks that time us. Cambridge, MA: Harvard University Press.
38.
MorinL.P. (1994). The circadian visual system. Brain Research Reviews, 19, 102–127.
NakagawaH., SackR.L., & LewyA.J. (1992). Sleep propensity free-runs with the temperature, Cortisol and melatonin rhythms in a totally blind person. Sleep, 15, 330–336.
41.
OkawaM., NanamiT., WadaS., ShimizuT., HishikawaY., SasakiH., NagamineH., & TakahashiK. (1987). Four congenitally blind children with circadian sleep-wake rhythm disorder. Sleep, 10, 101–110.
42.
OrthD.N., BesserG.M., KingP.H., & NicholsonW.E. (1979). Free-running circadian plasma Cortisol rhythm in a blind human subject. Clinical Endocrinology, 10, 603–617.
43.
PalmL., BlennowG., & WetterbergL. (1991). Correction of non-24-hour sleep/wake cycle by melatonin in a blind retarded boy. Annals of Neurology, 29, 336–339.
44.
PoeggelerB., BalzerI., HardelandR., & LerchlA. (1991) Pineal hormone melatonin oscillates also in the dinoflagellate Gonyaulax polyedra. Naturwissenschaften, 78, 268–269.
45.
ProvencioI., WongS., LedermanA.B., ArgarmasoS.M., & FosterR.G. (1994). Visual and circadian responses to light in aged retinally degenerate mice. Vision Research, 34, 1799–806.
46.
RalphM.R. (1991). Suprachiasmatic nucleus transplant studies using the tau mutation in golden hamsters. In KleinD.C., MooreR.Y. and ReppertS.M. (Eds.), Suprachiasmatic nucleus; the mind's clock (pp. 341–348). New York: Oxford University Press.
47.
RedmanJ., ArmstrongS., & NgK.T. (1983). Free-running activity rhythms in the rat: Entrainment by melatonin. Science, 219, 1089–1091.
48.
ReppertS.M., GodsonC., MahleC.D., WeaverD.R., SlaugenhouptS.A., & GusellaJ.F. (1995). Molecular characterization of a second melatonin receptor expressed in the human retina and brain: The Mel1b melatonin receptor. Proceedings of the National Academy of Science USA, 92, 8734–8738.
49.
ReppertS.M., WeaverD.R., & EbisawaT. (1994). Cloning and characterization of a mammalian melatonin receptor that mediates reproductive and circadian responses. Neuron, 13, 1177–1185.
50.
SackR.L., LewyA.J., BloodM.L., KeithL.D., & NakagawaH. (1992). Circadian rhythm abnormalities in totally blind people: Incidence and clinical significance. Journal of Clinical Endocrinology and Metabolism, 75, 127–134.
51.
SackR.L., LewyA.J., BloodM.L., StevensonJ., & KeithL.D. (1991). Melatonin administration to blind people: Phase advances and entrainment. Journal of Biological Rhythms, 6, 249–261.
52.
SackR.L., LewyA.J., & HobanT.M. (1987). Free running melatonin rhythms in blind people: Phase shifts with melatonin and triazolam administration. In RensingU., an der HeidenU., & MackeyM. C. (Eds.), Temporal disorder in human oscillatory systems (pp. 219–224). Heidelberg, Germany: Springer-Verlag.
53.
SackR.L., StevensonJ., & LewyA.J. (1990). Entrainment of a previously free-running blind human with melatonin administration. Sleep Research, 19, 404.
54.
SarrafzadehA., Wirz-JusticeA., ArendtJ., & EnglishJ. (1990). Melatonin stabilizes sleep onset in a blind man. In HomeJ.A. (Ed.), Sleep ‘90. (pp. 51–54). Bochum, Germany: Patenagel Press.
55.
ThorpyM.J. (1990) International Classification of Sleep Disorders: Diagnostic and coding manual.Rochester, MN, American Sleep Disorders Association.
56.
TurekF.W. (1989). Effects of stimulated physical activity on the circadian pacemaker of vertebrates. Journal of Biological Rhythms, 4, 135–148.
57.
TurekF.W. & Losee-OlsonS. (1986). A benzodiazepine used in the treatment of insomnia phase-shifts the mammalian circadian clock. Nature, 321, 167–168.
58.
TzischinskyO., PalI., EpsteinR., DaganY., & LavieP. (1992). The importance of timing in melatonin administration in a blind man. Journal of Pineal Research, 12, 105–108.
59.
Van CauterE., SturisJ., ByrneM.M., BlackmanJ.D., ScherbergN.H., LeproultR., RefetoffS., & Van ReethO. (1993). Preliminary studies on the immediate phase-shifting effects of light and exercise on the human circadian clock. Journal of Biological Rhythms, 8, S99–108.
60.
WalshJ., MuelbachM., & SchweitzerP. (1995). Hypnotics and caffeine as counter-measures for shiftwork-related sleepiness and sleep disturbance. Journal of Sleep Research, 4, 80–83.
61.
WeverR.A. (1979). The circadian system of man: Results of experiments under temporal isolation.New York: Springer-Verlag.
62.
ZulleyJ. & WeverR.A. (1982). Interaction between the sleep-wake cycle and the rhythm of rectal temperature. In AschoffJ., DaanS., & GroosG. (Eds.), Vertebrate circadian systems (pp. 253–261). Heidelberg, Germany: Springer-Verlag
