Sleep-Wake Cycles: Revealing the Hormonal Symphony of Melatonin and Circadian Rhythm Disorders - A Comprehensive Review
Abstract
Circadian rhythm (biological rhythm) disorders alter the body's natural sleep-wake cycles and have been associated with mood fluctuations, cardiovascular problems and cognitive degeneration. Notable disorders that result from an imbalance between an individual's internal circadian rhythms and external factors, such as light exposure and social responsibilities, can lead to conditions like delayed sleep-wake phase disorder (DSPD), advanced sleep phase syndrome (ASPD) and Shift work disorder (SWSD). The pineal gland secretes melatonin, a hormone that promotes sleep and indicates darkness to stabilize the circadian rhythms. This study explores the impact of melatonin on the suprachiasmatic nucleus (SCN), the brain's central clock, and its potential therapeutic applications for disorders that disrupt the circadian rhythm. Melatonin treatment lowers sleep onset latency (SOL), advances sleep-wake cycles in individuals with DSPD, and enhances morning alertness, according to clinical investigations. It improves the quality of sleep, which has some advantages for ASPD, especially in older persons. Melatonin lessens daytime drowsiness, eases insomnia, and helps sleep patterns adapt to work schedules for SWSD. In addition to discussing ideal dosage, possible adverse effects, and the necessity of customized care, this review highlights the significance of more research on the long-term safety of melatonin, medication interactions, and its application in combination therapy for disorders of the circadian rhythm.
Keywords:
Circadian rhythm disorders, melatonin supplementation, delayed sleep-wake phase disorder (DSPD), advanced sleep phase syndrome (ASPD), shift work disorder (SWSD), suprachiasmatic nucleus (SCN), sleep onset latency (SOL)DOI
https://doi.org/10.25004/References
Reppert SM, Weaver DR. Coordination of circadian timing in mammals. Nature. 2002;418(6901):935–941. Available from: doi.org/10.1038/nature00965
Roenneberg T, Merrow M. Circadian clocks – The fall and rise of physiology. Nat Rev Mol Cell Biol. 2005;6(12):965–971. Available from: doi.org/10.1038/nrm1766
Mohawk JA, Green CB, Takahashi JS. Central and peripheral circadian clocks in mammals. Annu Rev Neurosci. 2012;35:445–462. Available from: doi.org/10.1146/annurev-neuro-060909-153128
Sack RL, Auckley D, Auger RR, et al. Circadian rhythm sleep disorders: Part I, basic principles, shift work and jet lag disorders. Sleep. 2007;30(11):1460–1483. Available from: doi.org/10.1093/sleep/30.11.1460
Wright KP Jr, McHill AW. The circadian timing system and cardiovascular disease. Nat Rev Cardiol. 2017;14(3):151–161. Available from: doi.org/10.1038/nrcardio.2016.157
Crowley SJ, Eastman CI. Phase advancing human circadian rhythms with morning bright light, afternoon/evening melatonin, and gradually shifted sleep: Can we reduce morning bright-light duration? Sleep Med Rev. 2013;17(3):243–254. Available from: doi.org/10.1016/j.smrv.2012.07.002
Boivin DB, Boudreau P. Impacts of shift work on sleep and circadian rhythms. Pathol Biol (Paris). 2014;62(5):292–301. Available from: doi.org/10.1016/j.patbio.2014.08.001
Sack RL, Lewy AJ, Blood ML, et al. Circadian rhythm abnormalities in totally blind people: Incidence and clinical significance. J Clin Endocrinol Metab. 1992;75(1):127–134. Available from: doi.org/10.1210/jcem.75.1.1619018
Zisapel N. New perspectives on the role of melatonin in human sleep, circadian rhythms and their regulation. Br J Pharmacol. 2018;175(16):3190–3199. Available from: doi.org/10.1111/bph.14116
Burgess HJ, Revell VL, Eastman CI. A three-pulse phase response curve to three milligrams of melatonin in humans. J Physiol. 2008;586(2):639–647. Available from: doi.org/10.1113/jphysiol.2007.143180
Micic G, Lovato N, Gradisar M, Ferguson SA. Melatonin treatment for delayed sleep phase disorder: A systematic review. Sleep Med Rev. 2017;34:130–139. Available from: doi.org/10.1016/j.smrv.2016.07.005
Burgess JR, Fogg LF, Young MA. Effects of melatonin on sleep phase delay in adolescents with delayed sleep phase disorder: A randomized controlled trial. J Clin Sleep Med. 2017;13(4):419–427. Available from: doi.org/10.5664/jcsm.6530
Reid KJ, Zee PC. Circadian rhythm disorders. Semin Neurol. 2009;29(4):393–405. Available from: doi.org/10.1055/s-0029-1237110
Xu Y, Toh KL, Jones CR, et al. Modeling of a human circadian mutation yields insights into clock regulation by PER2. Cell. 2005;122(6):961–972. Available from: doi.org/10.1016/j.cell.2005.08.033
Reid KJ, Chang AM, Dubocovich ML, et al. Familial advanced sleep phase syndrome. Arch Neurol. 2011;58(7):1089–1094. Available from: doi.org/10.1001/archneur. 58.7.1089
Chung JC, Korman I. Melatonin in advanced sleep phase disorder: A review of evidence. Sleep Med. 2016;28:88–96. Available from: doi.org/10.1016/j.sleep.2016.09.013
Figueiro MG, Nagare R, Price LL. Non-visual effects of light: How to use light to promote circadian entrainment and elicit alertness. Sleep Med Rev. 2017;50(1):1–10. Available from: doi.org/10.1177/1477153517721598
Knutson KL, Ryden AM, Mander BA. Shift work and the incidence of obesity and metabolic syndrome. Sleep Med. 2006;7(6):425–429. Available from: doi.org/10.1016/j.sleep.2006.04.002
Akerstedt T. Shift work and health. Scand J Work Environ Health. 2007;33(2):89–104. Available from: doi.org/10.5271/sjweh.1119
Vgontzas AN, Kales A, Bixler EO. Insomnia and its consequences on health. Sleep Med Clin. 2013;8(2):237–250. Available from: doi.org/10.1016/j.jsmc.2013.04.004
Drake CL, Roehrs T, Roth T. Shift work and shift work disorder: A review. Sleep Med Rev. 2004;8(2):103–112. Available from: doi.org/10.1016/S1087-0792(03)00032-1
Liu PRK, Wang X. Melatonin for the treatment of shift work disorder: A systematic review and meta-analysis. Sleep Med Rev. 2018;37:49–59. Available from: doi.org/10.1016/j.smrv.2017.01.006
McGowan AE, Glozier N. Effectiveness of melatonin in shift work sleep disorder: A randomized controlled trial. Occup Med. 2017;67(6):442–449. Available from: doi.org/10.1093/occmed/kqx105
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