Reviews in Endocrine and Metabolic Disorders

, Volume 10, Issue 4, pp 245–260 | Cite as

Effects of circadian disruption on the cardiometabolic system

  • Melanie Rüger
  • Frank A. J. L. Scheer


The presence of day–night variations in cardiovascular and metabolic functioning is well known. However, only recently it has been shown that cardiovascular and metabolic processes are not only affected by the behavioral sleep/wake cycle but are partly under direct control of the master circadian pacemaker located in the suprachiasmatic nucleus (SCN). Heart rate, cardiac autonomic activity, glucose metabolism and leptin—involved in appetite control—all show circadian variation (i.e., under constant behavioral and environmental conditions). This knowledge of behavioral vs. circadian modulation of cardiometabolic function is of clinical relevance given the morning peak in adverse cardiovascular incidents observed in epidemiological studies and given the increased risk for the development of diabetes, obesity, and cardiovascular disease in shift workers. We will review the evidence for circadian control of cardiometabolic functioning, as well its sensitivity to light and melatonin, and discuss potential implication for therapy.


Cardiovascular system Circadian misalignment Light Metabolic function Shift work 



The authors would like to thank Dr. Steven W. Lockley for initial discussion. M.R. was supported by National Institute of Neurological disorders and Stroke Grant 5R01NS54277-3 and National Institute of Mental Health Grant 5R01MH45130-19. F.A.J.L.S. was supported by National Center for Complementary and Alternative Medicine Grant R21-AT002713, and Biomedical Research Institute Fund to Sustain Research Excellence from Brigham and Women’s Hospital.


  1. 1.
    Halberg F. Physiologic 24-hour periodicity; general and procedural considerations with reference to the adrenal cycle. Z Vitam Horm Formentforsch. 1959;10:225–96.Google Scholar
  2. 2.
    Muller JE. Circadian variation in cardiovascular events. Am J Hypertens. 1999;12:35S–42S.PubMedGoogle Scholar
  3. 3.
    Dethlefsen U, Repges R. Ein neues therapieprinzip bei nachtlichem asthma. Asthma Klin. 1985;80:44–7.Google Scholar
  4. 4.
    Pavlova MK, Shea SA, Bromfield EB. Day/night patterns of focal seizures. Epilepsy Behav. 2004;5:44–9.PubMedGoogle Scholar
  5. 5.
    Van Cauter E, Polonsky KS, Scheen AJ. Roles of circadian rhythmicity and sleep in human glucose regulation. Endocr Rev. 1997;18:716–38.Google Scholar
  6. 6.
    Shea SA, Scheer FA, Hilton MF. Predicting the daily pattern of asthma severity based on the relative contribution of the circadian timing system, the sleep-wake cycle and the environment. Sleep. 2007;30:A65.Google Scholar
  7. 7.
    Shea SA, Hilton MF, Orlova C, Ayers RT, Mantzoros CS. Independent circadian and sleep/wake regulation of adipokines and glucose in humans. J Clin Endocrinol Metab. 2005;90:2537–44.PubMedGoogle Scholar
  8. 8.
    Krantz DS, Kop WJ, Gabbay FH, Rozanski A, Barnard M, Klein J, Pardo Y, Gottdiener JS. Circadian variation of ambulatory myocardial ischemia. Triggering by daily activities and evidence for an endogenous circadian component. Circulation. 1996;93:1364–71.Google Scholar
  9. 9.
    Pavlova MK, Shea SA, Scheer FAJL, Bromfield EB. Is there a circadian variation of epileptiform abnormalities in idiopathic generalized epilepsy? Epilepsy and Behav. in press.Google Scholar
  10. 10.
    Young ME. The circadian clock within the heart: potential influence on myocardial gene expression, metabolism, and function. Am J Physiol Heart Circ Physiol. 2006;290:H1–16.PubMedGoogle Scholar
  11. 11.
    Scheer FAJL, Kalsbeek A, Buijs RM. Cardiovascular control by the suprachiasmatic nucleus: neural and neuroendocrine mechanisms in human and rat. Biol Chem. 2003;384:697–709.PubMedGoogle Scholar
  12. 12.
    Stephan FK, Zucker I. Rat drinking rhythms: central visual pathways and endocrine factors mediating responsiveness to environmental illumination. Physiol Behav. 1972;8:315–26.PubMedGoogle Scholar
  13. 13.
    Klein DC, Moore RY, Reppert SM. Suprachiasmatic nucleus: the mind’s clock. New York: Oxford University Press; 1991.Google Scholar
  14. 14.
    Reppert SM, Weaver DR. Coordination of circadian timing in mammals. Nature. 2002;418:935–41.PubMedGoogle Scholar
  15. 15.
    Marsh EE III, Biller J, Adams HP Jr, Marler JR, Hulbert JR, Love BB, et al. Circadian variation in onset of acute ischemic stroke. Arch Neurol. 1990;47:1178–80.PubMedGoogle Scholar
  16. 16.
    Gupta A, Shetty H. Circadian variation in stroke—a prospective hospital-based study. Int J Clin Pract. 2005;59:1272–5.PubMedGoogle Scholar
  17. 17.
    Muller JE, Stone PH, Turi ZG, Rutherford JD, Czeisler CA, Parker C, et al. Circadian variation in the frequency of onset of acute myocardial infarction. N Engl J Med. 1985;313:1315–22.PubMedGoogle Scholar
  18. 18.
    Marler JR, Price TR, Clark GL, Muller JE, Robertson T, Mohr JP, et al. Morning increase in onset of ischemic stroke. Stroke. 1989;20:473–6.PubMedGoogle Scholar
  19. 19.
    Tofler GH, Gebara OC, Mittleman MA, Taylor P, Siegel W, Venditti FJ Jr, et al. Morning peak in ventricular tachyarrhythmias detected by time of implantable cardioverter/defibrillator therapy. The CPI Investigators. Circulation. 1995;92:1203–8.PubMedGoogle Scholar
  20. 20.
    Manfredini R, Boari B, Smolensky MH, Salmi R, la Cecilia O, Maria MA, et al. Circadian variation in stroke onset: identical temporal pattern in ischemic and hemorrhagic events. Chronobiol Int. 2005;22:417–53.PubMedGoogle Scholar
  21. 21.
    Kuniyoshi FH, Garcia-Touchard A, Gami AS, Romero-Corral A, van der Walt C, Pusalavidyasagar S, et al. Day–night variation of acute myocardial infarction in obstructive sleep apnea. J Am Coll Cardiol. 2008;52:343–6.PubMedGoogle Scholar
  22. 22.
    Tofler GH, Brezinski D, Schafer AI, Czeisler CA, Rutherford JD, Willich SN, et al. Concurrent morning increase in platelet aggregability and the risk of myocardial infarction and sudden cardiac death. N Engl J Med. 1987;316:1514–8.PubMedGoogle Scholar
  23. 23.
    Brezinski DA, Tofler GH, Muller JE, Pohjola-Sintonen S, Willich SN, Schafer AI, Czeisler CA, Williams GH. Morning increase in platelet aggregability. Association with assumption of the upright posture. Circulation. 1988;78:35–40.Google Scholar
  24. 24.
    Scheer FA, Evoniuk H, Kelly E, Hahn M, Hu K, Malhotra A, Barnard MR, Frelinger III AL, Michelson AD, Shea SA. Effect of circadian system and behavioral stressors on platelet activity and reactivity: implications for the morning peak in cardiovascular incidents. Sleep. 2009;32:A47.Google Scholar
  25. 25.
    Kräuchi K, Wirz-Justice A. Circadian rhythm of heat production, heart rate, and skin and core temperature under unmasking conditions in men. Am J Physiol. 1994;267:R819–29.PubMedGoogle Scholar
  26. 26.
    Kerkhof GA, Van Dongen HPA, Bobbert AC. Absence of endogenous circadian rhythmicity in blood pressure? Am J Hypertens. 1998;11:373–7.PubMedGoogle Scholar
  27. 27.
    Duffy JF, Dijk DJ. Getting through to circadian oscillators: why use constant routines? J Biol Rhythms. 2002;17:4–13.PubMedGoogle Scholar
  28. 28.
    Van Dongen HPA, Maislin G, Kerkhof GA. Repeated assessment of the endogenous 24-hour profile of blood pressure under constant routine. Chronobiol Int. 2001;18:85–98.PubMedGoogle Scholar
  29. 29.
    Hu K, Ivanov PC, Hilton MF, Chen Z, Ayers RT, Stanley HE, et al. Endogenous circadian rhythm in an index of cardiac vulnerability independent of changes in behavior. Proc Natl Acad Sci U S A. 2004;101:18223–7.PubMedGoogle Scholar
  30. 30.
    Scheer FAJL, van Doornen LJP, Buijs RM. Light and diurnal cycle affect human heart rate: possible role for the circadian pacemaker. J Biol Rhythms. 1999;14:202–12.PubMedGoogle Scholar
  31. 31.
    Burgess HJ, Trinder J, Kim Y, Luke D. Sleep and circadian influences on cardiac autonomic nervous system activity. Am J Physiol Heart Circ Physiol. 1997;273:H1761–8.Google Scholar
  32. 32.
    van Eekelen AP, Houtveen JH, Kerkhof GA. Circadian variation in base rate measures of cardiac autonomic activity. Eur J Appl Physiol. 2004;93:39–46.PubMedGoogle Scholar
  33. 33.
    Ivanov PC, Hu K, Hilton MF, Shea SA, Stanley HE. Endogenous circadian rhythm in human motor activity uncoupled from circadian influences on cardiac dynamics. Proc Natl Acad Sci U S A. 2007;104:20702–7.PubMedGoogle Scholar
  34. 34.
    Force of the European Society of Cardiology and the North American Society of Pacing Electrophysiology. Heart rate variability. Standards of measurement, physiological interpretation, and clinical use. Circulation. 1996;93:1043–65.Google Scholar
  35. 35.
    Hilton MF, Umali MU, Czeisler CA, Wyatt JK, Shea SA. Endogenous circadian control of the human autonomic nervous system. Comput Cardiol. 2000;27:197–200.PubMedGoogle Scholar
  36. 36.
    Scheer FA, Van Doornen LJ, Buijs RM. Light and diurnal cycle affect autonomic cardiac balance in human; possible role for the biological clock. Auton Neurosci. 2004;110:44–8.Google Scholar
  37. 37.
    Huikuri HV, Makikallio TH. Heart rate variability in ischemic heart disease. Auton Neurosci. 2001;90:95–101.PubMedGoogle Scholar
  38. 38.
    Hu K, Scheer FA, Buijs RM, Shea SA. The endogenous circadian pacemaker imparts a scale-invariant pattern of heart rate fluctuations across time scales spanning minutes to 24 hours. J Biol Rhythms. 2008;23:265–73.Google Scholar
  39. 39.
    Hu K, Scheer FA, Buijs RM, Shea SA. The circadian pacemaker generates an endogenous circadian rhythm in the fractal structure of heart rate in rats. Cardiovasc Res. 2008;80:62–8.Google Scholar
  40. 40.
    Scheer FA, 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.PubMedGoogle Scholar
  41. 41.
    Van Cauter E, Blackman JD, Roland D, Spire JP, Refetoff S, Polonsky KS. Modulation of glucose regulation and insulin secretion by circadian rhythmicity and sleep. J Clin Invest. 1991;88:934–42.PubMedGoogle Scholar
  42. 42.
    Simon C, Gronfier C, Schlienger JL, Brandenberger G. Circadian and ultradian variations of leptin in normal man under continuous enteral nutrition: Relationship to sleep and body temperature. J Clin Endocrinol Metab. 1998;83:1893–9.PubMedGoogle Scholar
  43. 43.
    Scheer FAJL, Ter Horst GJ, van der Vliet J, Buijs RM. Physiological and anatomic evidence for regulation of the heart by suprachiasmatic nucleus in rats. Am J Physiol Heart Circ Physiol. 2001;280:H1391–9.PubMedGoogle Scholar
  44. 44.
    Scheer FA, Pirovano C, VanSomeren EJW, Buijs RM. Environmental light and suprachiasmatic nucleus interact in the regulation of body temperature. Neuroscience. 2005;132:465–77.PubMedGoogle Scholar
  45. 45.
    la Fleur SE, Kalsbeek A, Wortel J, Buijs RM. A suprachiasmatic nucleus generated rhythm in basal glucose concentrations. J Neuroendocrinol. 1999;11:643–52.PubMedGoogle Scholar
  46. 46.
    Kalsbeek A, Fliers E, Romijn JA, la Fleur SE, Wortel J, Bakker O, et al. The suprachiasmatic nucleus generates the diurnal changes in plasma leptin levels. Endocrinology. 2001;142:2677–85.PubMedGoogle Scholar
  47. 47.
    la Fleur SE, Kalsbeek A, Wortel J, Fekkes ML, Buijs RM. A daily rhythm in glucose tolerance: a role for the suprachiasmatic nucleus. Diabetes. 2001;50:1237–43.PubMedGoogle Scholar
  48. 48.
    Ruiter M, la Fleur SE, van Heijningen C, van der Vliet J, Kalsbeek A, Buijs RM. The daily rhythm in plasma glucagon concentrations in the rat is modulated by the biological clock and by feeding behavior. Diabetes. 2003;52:1709–15.PubMedGoogle Scholar
  49. 49.
    la Fleur SE, Kalsbeek A, Wortel J, Buijs RM. Polysynaptic neural pathways between the hypothalamus, including the suprachiasmatic nucleus, and the liver. Brain Res. 2000;871:50–6.PubMedGoogle Scholar
  50. 50.
    Buijs RM, Chun SJ, Niijima A, Romijn HJ, Nagai K. Parasympathetic and sympathetic control of the pancreas: a role for the suprachiasmatic nucleus and other hypothalamic centers that are involved in the regulation of food intake. J Comp Neurol. 2001;431:405–23.PubMedGoogle Scholar
  51. 51.
    Kreier F, Fliers E, Voshol PJ, Van Eden CG, Havekes LM, Kalsbeek A, et al. Selective parasympathetic innervation of subcutaneous and intra-abdominal fat-functional implications. J Clin Invest. 2002;110:1243–50.PubMedGoogle Scholar
  52. 52.
    Buijs RM, la Fleur SE, Wortel J, Van Heyningen C, Zuiddam L, Mettenleiter TC, et al. The suprachiasmatic nucleus balances sympathetic and parasympathetic output to peripheral organs through separate preautonomic neurons. J Comp Neurol. 2003;464:36–48.PubMedGoogle Scholar
  53. 53.
    Shibata S. Neural regulation of the hepatic circadian rhythm. Anat Rec A Discov Mol Cell Evol Biol. 2004;280:901–9.PubMedGoogle Scholar
  54. 54.
    Bartness TJ, Song CK, Demas GE. SCN efferents to peripheral tissues: implications for biological rhythms. J Biol Rhythms. 2001;16:196–204.PubMedGoogle Scholar
  55. 55.
    Czeisler CA, Allan JS, Strogatz SH, Ronda JM, Sánchez R, Ríos CD, et al. Bright light resets the human circadian pacemaker independent of the timing of the sleep-wake cycle. Science. 1986;233:667–71.PubMedGoogle Scholar
  56. 56.
    Czeisler CA, Kronauer RE, Allan JS, Duffy JF, Jewett ME, Brown EN, et al. Bright light induction of strong (type 0) resetting of the human circadian pacemaker. Science. 1989;244:1328–33.PubMedGoogle Scholar
  57. 57.
    Boivin DB, Duffy JF, Kronauer RE, Czeisler CA. Sensitivity of the human circadian pacemaker to moderately bright light. J Biol Rhythms. 1994;9:315–31.PubMedGoogle Scholar
  58. 58.
    Lockley SW, Brainard GC, Czeisler CA. High sensitivity of the human circadian melatonin rhythm to resetting by short wavelength light. J Clin Endocrinol Metab. 2003;88:4502–5.PubMedGoogle Scholar
  59. 59.
    Harrington ME. The ventral lateral geniculate nucleus and the intergeniculate leaflet: interrelated structures in the visual and circadian systems. Neurosci Biobehav Rev. 1997;21:705–27.PubMedGoogle Scholar
  60. 60.
    Moore RY. Organization of the mammalian circadian system. In: Waterhouse JM, editor. Circadian clocks and their adjustment. Chichester (Ciba Foundation Symp 183): John Wiley and Sons, Inc.; 1995. p. 88–99.Google Scholar
  61. 61.
    Berson DM, Dunn FA, Takao M. Phototransduction by retinal ganglion cells that set the circadian clock. Science. 2002;295:1070–3.PubMedGoogle Scholar
  62. 62.
    Berson DM. Strange vision: ganglion cells as circadian photoreceptors. Trends Neurosci. 2003;26:314–20.PubMedGoogle Scholar
  63. 63.
    Hattar S, Liao H-W, Takao M, Berson DM, Yau K-W. Melanopsin-containing retinal ganglion cells: architecture, projections, and intrinsic photosensitivity. Science. 2002;295:1065–70.PubMedGoogle Scholar
  64. 64.
    Provencio I, Rodriguez IR, Jiang G, Hayes WP, Moreira EF, Rollag MD. A novel human opsin in the inner retina. J Neurosci. 2000;20:600–5.PubMedGoogle Scholar
  65. 65.
    Dai J, van der Vliet J, Swaab DF, Buijs RM. Human retinohypothalamic tract as revealed by in vitro postmortem tracing. J Comp Neurol. 1998;397:357–70.PubMedGoogle Scholar
  66. 66.
    Sadun AA, Schaechter JD, Smith LEH. A retinohypothalamic pathway in man: light mediation of circadian rhythms. Brain Res. 1984;302:371–7.PubMedGoogle Scholar
  67. 67.
    Friedman DI, Johnson JK, Chorsky RL, Stopa EG. Labeling of human retinohypothalamic tract with the carbocyanine dye, DiI. Brain Res. 1991;560:297–302.PubMedGoogle Scholar
  68. 68.
    Hattar S, Lucas RJ, Mrosovsky N, Thompson S, Douglas RH, Hankins MW, et al. Melanopsin and rod-cone photoreceptive systems account for all major accessory visual functions in mice. Nature. 2003;424:76–81.PubMedGoogle Scholar
  69. 69.
    Lucas RJ, Foster RG. Neither functional rod photoreceptors nor rod or cone outer segments are required for the photic inhibition of pineal melatonin. Endocrinology. 1999;140:1520–4.PubMedGoogle Scholar
  70. 70.
    Lucas RJ, Douglas RH, Foster RG. Characterization of an ocular photopigment capable of driving pupillary constriction in mice. Nat Neurosci. 2001;4:621–6.PubMedGoogle Scholar
  71. 71.
    Lucas RJ, Hattar S, Takao M, Berson DM, Foster RG, Yau K-W. Diminished pupillary light reflex at high irradiance in melanopsin-knockout mice. Science. 2003;299:245–7.PubMedGoogle Scholar
  72. 72.
    Moore RY, Speh JC, Card JP. The retinohypothalamic tract originates from a distinct subset of retinal ganglion cells. J Comp Neurol. 1995;352:351–66.PubMedGoogle Scholar
  73. 73.
    Gooley JJ, Lu J, Chou TC, Scammell TE, Saper CB. Melanopsin in cells of origin of the retinohypothalamic tract. Nat Neurosci. 2001;4:1165.PubMedGoogle Scholar
  74. 74.
    Takahashi JS, DeCoursey PJ, Bauman L, Menaker M. Spectral sensitivity of a novel photoreceptive system mediating entrainment of mammalian circadian rhythms. Nature. 1984;308:186–8.PubMedGoogle Scholar
  75. 75.
    Thapan K, Arendt J, Skene DJ. An action spectrum for melatonin suppression: evidence for a novel non-rod, non-cone photoreceptor system in humans. J Physiol. 2001;535:261–7.PubMedGoogle Scholar
  76. 76.
    Selby CP, Thompson C, Schmitz TM, Van Gelder RN, Sancar A. Functional redundancy of cryptochromes and classical photoreceptors for nonvisual ocular photoreception in mice. Proc Natl Acad Sci USA. 2000;97:14697–702.PubMedGoogle Scholar
  77. 77.
    Brainard GC, Hanifin JP, Rollag MD, Greeson J, Byrne B, Glickman G, et al. Human melatonin regulation is not mediated by the three cone photopic visual system. J Clin Endocrinol Metab. 2001;86:433–6.PubMedGoogle Scholar
  78. 78.
    Brainard GC, Hanifin JP, Greeson JM, Byrne B, Glickman G, Gerner E, et al. Action spectrum for melatonin regulation in humans: evidence for a novel circadian photoreceptor. J Neurosci. 2001;21(16):6405–12.PubMedGoogle Scholar
  79. 79.
    Miyamoto Y, Sancar A. Vitamin B2-based blue-light photoreceptors in the retinohypothalmic tract as the photoactive pigments for setting the circadian clock in mammals. Proc Natl Acad Sci USA. 1998;95:6097–102.PubMedGoogle Scholar
  80. 80.
    Honma K, Honma S. A human phase response curve for bright light pulses. Jpn J Psychiatry Neurol. 1988;42:167–8.Google Scholar
  81. 81.
    Khalsa SBS, Jewett ME, Cajochen C, Czeisler CA. A phase response curve to single bright light pulses in human subjects. J Physiol (Lond). 2003;549:945–52.Google Scholar
  82. 82.
    Minors DS, Waterhouse JM, Wirz-Justice A. A human phase-response curve to light. Neurosci Lett. 1991;133:36–40.PubMedGoogle Scholar
  83. 83.
    Beersma DGM, Daan S. Strong or weak phase resetting by light pulses in humans? J Biol Rhythms. 1993;8:340–7.PubMedGoogle Scholar
  84. 84.
    Smith KA, Schoen MW, Czeisler CA. Adaptation of human pineal melatonin suppression by recent photic history. J Clin Endocrinol Metab. 2004;89:3610–4.Google Scholar
  85. 85.
    Jasser SA, Hanifin JP, Rollag MD, Brainard GC. Dim light adaptation attenuates acute melatonin suppression in humans. J Biol Rhythms. 2006;21:394–404.Google Scholar
  86. 86.
    Campos LA, Plehm R, Cipolla-Neto J, Bader M, Baltatu OC. Altered circadian rhythm reentrainment to light phase shifts in rats with low levels of brain angiotensinogen. Am J Physiol Regul Integr Comp Physiol. 2006;290:R1122–7.PubMedGoogle Scholar
  87. 87.
    Vandewalle G, Middleton B, Rajaratnam SM, Stone BM, Thorleifsdottir B, Arendt J, et al. Robust circadian rhythm in heart rate and its variability: influence of exogenous melatonin and photoperiod. J Sleep Res. 2007;16:148–55.PubMedGoogle Scholar
  88. 88.
    Rajaratnam SM, Middleton B, Stone BM, Arendt J, Dijk DJ. Melatonin advances the circadian timing of EEG sleep and directly facilitates sleep without altering its duration in extended sleep opportunities in humans. J Physiol. 2004;561:339–51.PubMedGoogle Scholar
  89. 89.
    Rüger M, Gordijn MC, Beersma DG, de Vries B, Daan S. Time-of-day-dependent effects of bright light exposure on human psychophysiology: comparison of daytime and nighttime exposure. Am J Physiol Regul Integr Comp Physiol. 2006;290:R1413–20.PubMedGoogle Scholar
  90. 90.
    Tsunoda M, Endo T, Hashimoto S, Honma S, Honma K-I. Effects of light and sleep stages on heart rate variability in humans. Psychiatr Clin Neurosci. 2001;55:286.Google Scholar
  91. 91.
    Burgess HJ, Sletten T, Savic N, Gilbert SS, Dawson D. Effects of bright light and melatonin on sleep propensity, temperature, and cardiac activity at night. J Appl Physiol. 2001;91:1214–22.PubMedGoogle Scholar
  92. 92.
    Yokoi M, Aoki K, Shimomura Y, Iwanaga K, Katsuura T. Exposure to bright light modifies HRV responses to mental tasks during nocturnal sleep deprivation. J Physiol Anthropol. 2006;25:153–61.PubMedGoogle Scholar
  93. 93.
    Cajochen C, Munch M, Kobialka S, Krauchi K, Steiner R, Oelhafen P, et al. High sensitivity of human melatonin, alertness, thermoregulation, and heart rate to short wavelength light. J Clin Endocrinol Metab. 2005;90:1311–6.PubMedGoogle Scholar
  94. 94.
    Lockley SW, Evans EE, Scheer FAJL, Brainard GC, Czeisler CA, Aeschbach D. Short-wavelength sensitivity for the direct effects of light on alertness, vigilance, and the waking electroencephalogram in humans. Sleep. 2006;29:161–8.PubMedGoogle Scholar
  95. 95.
    Warman VL, Dijk DJ, Warman GR, Arendt J, Skene DJ. Phase advancing human circadian rhythms with short wavelength light. Neurosci Lett. 2003;342:37–40.PubMedGoogle Scholar
  96. 96.
    Kudielka BM, Kirschbaum C. Awakening cortisol responses are influenced by health status and awakening time but not by menstrual cycle phase. Psychoneuroendocrinology. 2003;28:35–47.PubMedGoogle Scholar
  97. 97.
    Scheer FAJL, Buijs RM. Light affects morning salivary cortisol in humans. J Clin Endocrinol Metab. 1999;84:3395–8.PubMedGoogle Scholar
  98. 98.
    Leproult R, Colecchia EF, L’Hermite-Balériaux M, Van Cauter E. Transition from dim to bright light in the morning induces an immediate elevation of cortisol levels. J Clin Endocrinol Metab. 2001;86:151–7.PubMedGoogle Scholar
  99. 99.
    Thorn L, Hucklebridge F, Esgate A, Evans P, Clow A. The effect of dawn simulation on the cortisol response to awakening in healthy participants. Psychoneuroendocrinology. 2004;29(7):925–30.PubMedGoogle Scholar
  100. 100.
    Badia P, Culpepper J, Myers B, Boecker M, Harsh J. Psychophysiological and behavioral effects of bright and dim light. In: Chase MH, Lydic R, O’Connor C, editors. Sleep research. Los Angeles: Brain Information Service; 1990. p. 387.Google Scholar
  101. 101.
    Badia P, Myers B, Boecker M, Culpepper J, Harsch JR. Bright light effects on body temperature, alertness, EEG and behavior. Physiol Behav. 1991;50:583–8.PubMedGoogle Scholar
  102. 102.
    Rüger M, Gordijn MC, Beersma DG, de Vries B, Daan S. Acute and phase-shifting effects of ocular and extraocular light in human circadian physiology. J Biol Rhythms. 2003;18:409–19.PubMedGoogle Scholar
  103. 103.
    Kubota T, Uchiyama M, Suzuki H, Shibui K, Kim K, Tan X, et al. Effects of nocturnal bright light on saliva melatonin, core body temperature and sleep propensity rhythms in human subjects. Neurosci Res. 2002;42:115–22.PubMedGoogle Scholar
  104. 104.
    Lewy AJ, Wehr TA, Goodwin FK, Newsome DA, Markey SP. Light suppresses melatonin secretion in humans. Science. 1980;210:1267–9.PubMedGoogle Scholar
  105. 105.
    Shanahan TL, Czeisler CA. Light exposure induces equivalent phase shifts of the endogenous circadian rhythms of circulating plasma melatonin and core body temperature in men. J Clin Endocrinol Metab. 1991;73:227–35.PubMedGoogle Scholar
  106. 106.
    Buijs RM, Wortel J, Van Heerikhuize JJ, Feenstra MG, Ter Horst GJ, Romijn HJ, Kalsbeek A. Anatomical and functional demonstration of a multisynaptic suprachiasmatic nucleus adrenal (cortex) pathway. Eur J Neurosci. 1999;11:1535–44.Google Scholar
  107. 107.
    Scheer FA, Czeisler CA. Melatonin, sleep, and circadian rhythms. Sleep Med Rev. 2005;9:5–9.PubMedGoogle Scholar
  108. 108.
    Scheer FA, Cajochen C, Turek FW, Czeisler CA. Melatonin in the regulation of sleep and circadian rhythms. In: Kryger MH, Roth T, Dement WC, editors. Principles and practice of sleep medicine. Philadelphia: Saunders; 2005. p. 395–404.Google Scholar
  109. 109.
    Birau N, Peterssen U, Meyer C, Gottschalk J. Hypotensive effect of melatonin in essential hypertension. IRCS Med Sci. 1981;9:906.Google Scholar
  110. 110.
    Cagnacci A, Zanni AL, Venerit MG, Menozzi R, Volpe A, Del Riot G. Influence of exogenous melatonin on catecholamine levels inpostmenopausal woman prior and during oestradiol replacement. Clin Endocrinol. 2000;53:367–72.Google Scholar
  111. 111.
    Lusardi P, Piazza E, Fogari R. Cardiovascular effects of melatonin in hypertensive patients well controlled by nifedipine: a 24-hour study. Br J Clin Pharmacol. 2000;49:423–7.PubMedGoogle Scholar
  112. 112.
    Scheer FA, Van Montfrans GA, Van Someren EJ, Mairuhu G, Buijs RM. Daily nighttime melatonin reduces blood pressure in male patients with essential hypertension. Hypertension. 2004;43:192–7.PubMedGoogle Scholar
  113. 113.
    Cagnacci A, Cannoletta M, Renzi A, Baldassari F, Arangino S, Volpe A. Prolonged melatonin administration decreases nocturnal blood pressure in women. Am J Hypertens. 2005;18:1614–8.PubMedGoogle Scholar
  114. 114.
    Grossman E, Laudon M, Yalcin R, Zengil H, Peleg E, Sharabi Y, et al. Melatonin reduces night blood pressure in patients with nocturnal hypertension. Am J Med. 2006;119:898–902.PubMedGoogle Scholar
  115. 115.
    Wu YH, Zhou JN, Balesar R, Unmehopa U, Bao A, Jockers R, et al. Distribution of MT1 melatonin receptor immunoreactivity in the human hypothalamus and pituitary gland: colocalization of MT1 with vasopressin, oxytocin, and corticotropin-releasing hormone. J Comp Neurol. 2006;499:897–910.PubMedGoogle Scholar
  116. 116.
    Ekmekcioglu C, Haslmayer P, Philipp C, Mehrabi MR, Glogar HD, Grimm M, et al. Expression of the MT1 melatonin receptor subtype in human coronary arteries. J Recept Signal Transduct Res. 2001;21:85–91.PubMedGoogle Scholar
  117. 117.
    Tengattini S, Reiter RJ, Tan DX, Terron MP, Rodella LF, Rezzani R. Cardiovascular diseases: protective effects of melatonin. J Pineal Res. 2008;44:16–25.PubMedGoogle Scholar
  118. 118.
    Kräuchi K, Cajochen C, Möri D, Graw P, Wirz-Justice A. Early evening melatonin and S-20098 advanced circadian phase and nocturnal regulation of core body temperature. Am J Physiol. 1997;272:R1178–88.PubMedGoogle Scholar
  119. 119.
    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.PubMedGoogle Scholar
  120. 120.
    Vener KJ, Szabo S, Moore JG. The effect of shift work on gastrointestinal (GI) function: a review. Chronobiologia. 1989;16:421–39.PubMedGoogle Scholar
  121. 121.
    Czeisler CA, Moore-Ede MC, Coleman RM. Rotating shift work schedules that disrupt sleep are improved by applying circadian principles. Science. 1982;217:460–3.PubMedGoogle Scholar
  122. 122.
    Czeisler CA, Dijk DJ. Use of bright light to treat maladaption to night shift work and circadian rhythm sleep disorders. J Sleep Res. 1995;4:70–3.PubMedGoogle Scholar
  123. 123.
    Czeisler CA, Chiasera AJ, Duffy JF. Research on sleep, circadian rhythms and aging: applications to manned spaceflight. Exp Gerontol. 1991;26:217–32.PubMedGoogle Scholar
  124. 124.
    Schwartz WJ, Busis NA, Hedley Whyte ET. A discrete lesion of ventral hypothalamus and optic chiasm that disturbed the daily temperature rhythm. J Neurol. 1986;233:1–4.Google Scholar
  125. 125.
    Cohen RA, Albers HE. Disruption of human circadian and cognitive regulation following a discrete hypothalamic lesion: a case study. Neurology. 1991;41:726–29.Google Scholar
  126. 126.
    Lipton J, Megerian JT, Kothare SV, Cho YJ, Shanahan T, Chart H, Ferber R, Adler-Golden L, Cohen LE, Czeisler CA, Pomeroy SL. Melatonin deficiency and disrupted circadian rhythms in pediatric survivors of craniopharyngioma. Neurology. 2009;73:323–5.Google Scholar
  127. 127.
    Wu YH, Fischer DF, Kalsbeek A, Garidou-Boof ML, van der Vliet J, van Heijningen C, Liu RY, Zhou JN, Swaab DF. Pineal clock gene oscillation is disturbed in Alzheimer’s disease, due to functional disconnection from the “master clock”. FASEB J. 2006;20:1874–6.Google Scholar
  128. 128.
    Zhou JN, Riemersma RF, Unmehopa UA, Hoogendijk WJ, van Heerikhuize JJ, Hofman MA, Swaab DF. Alterations in arginine vasopressin neurons in the suprachiasmatic nucleus in depression. Arch Gen Psychiatry. 2001;58(7):655–62.Google Scholar
  129. 129.
    Knutsson A. Health disorders of shift workers. Occup Med (Lond). 2003;53:103–8.Google Scholar
  130. 130.
    Knutsson A. Shift work and coronary heart disease. Scand J Soc Med Suppl. 1989;44:1–36.PubMedGoogle Scholar
  131. 131.
    Wolk R, Gami AS, Garcia-Touchard A, Somers VK. Sleep and cardiovascular disease. Curr Probl Cardiol. 2005;30:625–62.PubMedGoogle Scholar
  132. 132.
    Haus E, Smolensky M. Biological clocks and shift work: circadian dysregulation and potential long-term effects. Cancer Causes Control. 2006;17:489–500.PubMedGoogle Scholar
  133. 133.
    Schernhammer ES, Laden F, Speizer FE, Willett WC, Hunter DJ, Kawachi I, Fuchs CS, Colditz GA. Night-shift work and risk of colorectal cancer in the nurses’ health study. J Natl Cancer Inst. 2003;95:825–8.Google Scholar
  134. 134.
    Knutsson A, Åkerstedt T, Jonsson BG, Orth-Gomer K. Increased risk of ischaemic heart disease in shift workers. Lancet. 1986;2:89–92.PubMedGoogle Scholar
  135. 135.
    Kawachi I, Colditz GA, Stampfer MJ, Willett WC, Manson JE, Speizer FE, et al. Prospective study of shift work and risk of coronary heart disease in women. Circulation. 1995;92:3178–82.PubMedGoogle Scholar
  136. 136.
    Tenkanen L, Sjoblom T, Kalimo R, Alikoski T, Harma M. Shift work, occupation and coronary heart disease over 6 years of follow-up in the Helsinki Heart Study. Scand J Work Environ Health. 1997;23:257–65.PubMedGoogle Scholar
  137. 137.
    Karlsson B, Knutsson A, Lindahl B. Is there an association between shiftwork and having a metabolic syndrome? Results from a population based study of 27485 people. Occup Environ Med. 2001;58:747–52.PubMedGoogle Scholar
  138. 138.
    Lund J, Arendt J, Hampton SM, English J, Morgan LM. Postprandial hormone and metabolic responses amongst shift workers in Antarctica. J Endocrinol. 2001;171:557–64.PubMedGoogle Scholar
  139. 139.
    Morikawa Y, Nakagawa H, Miura K, Soyama Y, Ishizaki M, Kido T, et al. Shift work and the risk of diabetes mellitus among Japanese male factory workers. Scand J Work Environ Health. 2005;31:179–83.PubMedGoogle Scholar
  140. 140.
    Kroenke CH, Spiegelman D, Manson J, Schernhammer ES, Colditz GA, Kawachi I. Work characteristics and incidence of type 2 diabetes in women. Am J Epidemiol. 2007;165:175–83.PubMedGoogle Scholar
  141. 141.
    Biggi N, Consonni D, Galluzzo V, Sogliani M, Costa G. Metabolic syndrome in permanent night workers. Chronobiol Int. 2008;25:443–54.PubMedGoogle Scholar
  142. 142.
    Filipski E, King VM, Li X, Granda TG, Mormont M-C, Liu X, et al. Host circadian clock as a control point in tumor progression. J Natl Cancer Inst. 2002;94:690–7.PubMedGoogle Scholar
  143. 143.
    Rafnsson V, Tulinius H, Jonasson JG, Hrafnkelsson J. Risk of breast cancer in female flight attendants: a population-based study (Iceland). Cancer Causes Control. 2001;12:95–101.PubMedGoogle Scholar
  144. 144.
    Hampton SM, Morgan LM, Lawrence N, Anastasiadou T, Norris F, Deacon S, et al. Postprandial hormone and metabolic responses in simulated shift work. J Endocrinol. 1996;151:259–67.PubMedGoogle Scholar
  145. 145.
    Ribeiro D, Hampton SM, Morgan L, Deacon S, Arendt J. Altered postprandial hormone and metabolic responses in a simulated shift work environment. J Endocrinol. 1998;158:305–10.PubMedGoogle Scholar
  146. 146.
    Dijk DJ, Czeisler CA. Paradoxical timing of the circadian rhythm of sleep propensity serves to consolidate sleep and wakefulness in humans. Neurosci Lett. 1994;166:63–8.PubMedGoogle Scholar
  147. 147.
    Spiegel K, Leproult R, Van Cauter E. Impact of sleep debt on metabolic and endocrine function. Lancet. 1999;354:1435–9.PubMedGoogle Scholar
  148. 148.
    Garcia GV, Freeman RV, Supiano MA, Smith MJ, Galecki AT, Halter JB. Glucose metabolism in older adults: a study including subjects more than 80 years of age. J Am Geriatr Soc. 1997;45:813–7.PubMedGoogle Scholar
  149. 149.
    Spiegel K, Leproult R, L’Hermite-Balériaux M, Copinschi G, Penev PD, Van Cauter E. Leptin levels are dependent on sleep duration: relationships with sympathovagal balance, carbohydrate regulation, cortisol, and thyrotropin. J Clin Endocrinol Metab. 2004;89:5762–71.PubMedGoogle Scholar
  150. 150.
    Spiegel K, Tasali E, Penev P, Van Cauter E. Brief communication: Sleep curtailment in healthy young men is associated with decreased leptin levels, elevated ghrelin levels, and increased hunger and appetite. Ann Intern Med. 2004;141:846–50.PubMedGoogle Scholar
  151. 151.
    Nedeltcheva AV, Kilkus JM, Imperial J, Kasza K, Schoeller DA, Penev PD. Sleep curtailment is accompanied by increased intake of calories from snacks. Am J Clin Nutr. 2009;89:126–33.PubMedGoogle Scholar
  152. 152.
    Knutson KL, Van Cauter E. Associations between sleep loss and increased risk of obesity and diabetes. Ann NY Acad Sci. 2008;1129:287–304.PubMedGoogle Scholar
  153. 153.
    Bruehl H, Rueger M, Dziobek I, Sweat V, Tirsi A, Javier E, et al. Hypothalamic-pituitary-adrenal axis dysregulation and memory impairments in type 2 diabetes. J Clin Endocrinol Metab. 2007;92:2439–45.PubMedGoogle Scholar
  154. 154.
    Convit A, Rueger M, Wolf OT. Diabetes type 2 and stress: impact on memory and the hippocampus. In: Squire LR, editor. Encyclopedia of neuroscience. Oxford: Academic; 2009. p. 503–9.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Division of Sleep Medicine, Harvard Medical SchoolBrigham and Women’s HospitalBostonUSA

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