Editing Circadian rhythm (section)

=== Consequences of disruption to circadian rhythms ===

==== Disruption ====
{{Further|Circadian rhythm sleep disorder}}
Disruption to rhythms usually has a negative effect. Many travelers have experienced the condition known as [[jet lag]], with its associated symptoms of [[fatigue (physical)|fatigue]], [[disorientation]] and [[insomnia]].<ref>{{Cite web |title=The science of jet lag |url=https://www.timeshifter.com/jet-lag/the-science-of-jet-lag |access-date=2023-01-03 |website=Timeshifter |language=en}}</ref>

A number of other disorders, such as [[bipolar disorder]], [[Major depressive disorder|depression]], and some [[sleep disorder]]s such as [[delayed sleep phase disorder]] (DSPD), are associated with irregular or pathological functioning of circadian rhythms.<ref>{{cite journal | vauthors = Gold AK, Kinrys G | title = Treating Circadian Rhythm Disruption in Bipolar Disorder | journal = Current Psychiatry Reports | volume = 21 | issue = 3 | pages = 14 | date = March 2019 | pmid = 30826893 | pmc = 6812517 | doi = 10.1007/s11920-019-1001-8 }}</ref><ref>{{cite journal | vauthors = Zhu L, Zee PC | title = Circadian rhythm sleep disorders | journal = Neurologic Clinics | volume = 30 | issue = 4 | pages = 1167–1191 | date = November 2012 | pmid = 23099133 | pmc = 3523094 | doi = 10.1016/j.ncl.2012.08.011 }}</ref><ref>{{Cite journal |last1=Crouse |first1=Jacob J |last2=Carpenter |first2=Joanne S |last3=Song |first3=Yun Ju C |last4=Hockey |first4=Samuel J |last5=Naismith |first5=Sharon L |last6=Grunstein |first6=Ronald R |last7=Scott |first7=Elizabeth M |last8=Merikangas |first8=Kathleen R |last9=Scott |first9=Jan |last10=Hickie |first10=Ian B |date=September 2021 |title=Circadian rhythm sleep–wake disturbances and depression in young people: implications for prevention and early intervention |url=https://linkinghub.elsevier.com/retrieve/pii/S2215036621000341 |journal=The Lancet Psychiatry |language=en |volume=8 |issue=9 |pages=813–823 |doi=10.1016/S2215-0366(21)00034-1|pmid=34419186 }}</ref><ref>{{Cite journal |last1=Scott |first1=Jan |last2=Etain |first2=Bruno |last3=Miklowitz |first3=David |last4=Crouse |first4=Jacob J. |last5=Carpenter |first5=Joanne |last6=Marwaha |first6=Steven |last7=Smith |first7=Daniel |last8=Merikangas |first8=Kathleen |last9=Hickie |first9=Ian |date=April 2022 |title=A systematic review and meta-analysis of sleep and circadian rhythms disturbances in individuals at high-risk of developing or with early onset of bipolar disorders |journal=Neuroscience & Biobehavioral Reviews |language=en |volume=135 |pages=104585 |doi=10.1016/j.neubiorev.2022.104585 |pmc=8957543 |pmid=35182537}}</ref>

Disruption to rhythms in the longer term is believed to have significant adverse health consequences for peripheral organs outside the brain, in particular in the development or exacerbation of cardiovascular disease.<ref name="Zelinski2014">{{cite journal | vauthors = Zelinski EL, Deibel SH, McDonald RJ | title = The trouble with circadian clock dysfunction: multiple deleterious effects on the brain and body | journal = Neuroscience and Biobehavioral Reviews | volume = 40 | issue = 40 | pages = 80–101 | date = March 2014 | pmid = 24468109 | doi = 10.1016/j.neubiorev.2014.01.007 | s2cid = 6809964 }}</ref><ref>Oritz-Tuldela E, Martinez-Nicolas A, Diaz-Mardomingo C, Garcia-Herranz S, Pereda-Perez I, Valencia A, Peraita H, Venero C, Madrid J, Rol M. 2014. The Characterization of Biological Rhythms in Mild Cognitive Impairment. BioMed Research International.</ref>

Studies have shown that maintaining normal sleep and circadian rhythms is important for many aspects of brain and health.<ref name="Zelinski2014" /> A number of studies have also indicated that a [[power-nap]], a short period of sleep during the day, can reduce stress and may improve productivity without any measurable effect on normal circadian rhythms.<ref>{{cite journal | vauthors = Hershner SD, Chervin RD | title = Causes and consequences of sleepiness among college students | journal = Nature and Science of Sleep | volume = 6 | pages = 73–84 | date = 2014-06-23 | pmid = 25018659 | pmc = 4075951 | doi = 10.2147/NSS.S62907 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Milner CE, Cote KA | title = Benefits of napping in healthy adults: impact of nap length, time of day, age, and experience with napping | journal = Journal of Sleep Research | volume = 18 | issue = 2 | pages = 272–281 | date = June 2009 | pmid = 19645971 | doi = 10.1111/j.1365-2869.2008.00718.x | s2cid = 22815227 | doi-access = free }}</ref><ref>{{cite book | vauthors = Lovato N, Lack L |title=The effects of napping on cognitive functioning |year=2010 |isbn=978-0-444-53702-7 |series=Progress in Brain Research |volume=185 |pages=155–166 |doi=10.1016/B978-0-444-53702-7.00009-9 |pmid=21075238 }}</ref> Circadian rhythms also play a part in the [[reticular activating system]], which is crucial for maintaining a state of consciousness. A reversal{{Clarify|date=April 2019}} in the sleep–wake cycle may be a sign or complication of [[uremia]],<ref>{{cite web |date=10 May 2006 |title=Renal Failure, Acute |url=http://www.emedicine.com/emerg/topic500.htm |access-date=2008-08-03 |publisher=eMedicine from WebMD |vauthors=Sinert T, Peacock PR}}</ref> [[azotemia]] or [[acute kidney injury]].<ref>{{cite journal | vauthors = Maung SC, El Sara A, Chapman C, Cohen D, Cukor D | title = Sleep disorders and chronic kidney disease | journal = World Journal of Nephrology | volume = 5 | issue = 3 | pages = 224–232 | date = May 2016 | pmid = 27152260 | pmc = 4848147 | doi = 10.5527/wjn.v5.i3.224 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Nakano S, Uchida K, Kigoshi T, Azukizawa S, Iwasaki R, Kaneko M, Morimoto S | title = Circadian rhythm of blood pressure in normotensive NIDDM subjects. Its relationship to microvascular complications | journal = Diabetes Care | volume = 14 | issue = 8 | pages = 707–711 | date = August 1991 | pmid = 1954805 | doi = 10.2337/diacare.14.8.707 | s2cid = 12489921 }}</ref> Studies have also helped elucidate how light has a [[Light effects on circadian rhythm|direct effect]] on human health through its influence on the circadian biology.<ref>{{cite journal | vauthors = Figueiro MG, Rea MS, Bullough JD | title = Does architectural lighting contribute to breast cancer? | journal = Journal of Carcinogenesis | volume = 5 | pages = 20 | date = August 2006 | pmid = 16901343 | pmc = 1557490 | doi = 10.1186/1477-3163-5-20 | doi-access = free }}</ref>

==== Relationship with cardiovascular disease ====

One of the first studies to determine how disruption of circadian rhythms causes cardiovascular disease was performed in the Tau hamsters, which have a genetic defect in their circadian clock mechanism.<ref name="Circadian rhythm disorganization pr">{{cite journal | vauthors = Martino TA, Oudit GY, Herzenberg AM, Tata N, Koletar MM, Kabir GM, Belsham DD, Backx PH, Ralph MR, Sole MJ | title = Circadian rhythm disorganization produces profound cardiovascular and renal disease in hamsters | journal = American Journal of Physiology. Regulatory, Integrative and Comparative Physiology | volume = 294 | issue = 5 | pages = R1675–R1683 | date = May 2008 | pmid = 18272659 | doi = 10.1152/ajpregu.00829.2007 | s2cid = 13356393 }}</ref> When maintained in a 24-hour light-dark cycle that was "out of sync" with their normal 22 circadian mechanism they developed profound cardiovascular and renal disease; however, when the Tau animals were raised for their entire lifespan on a 22-hour daily light-dark cycle they had a healthy cardiovascular system.<ref name="Circadian rhythm disorganization pr"/> The adverse effects of circadian misalignment on human physiology has been studied in the laboratory using a misalignment protocol,<ref>{{cite journal | vauthors = Scheer FA, Hilton MF, Mantzoros CS, Shea SA | title = Adverse metabolic and cardiovascular consequences of circadian misalignment | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 11 | pages = 4453–4458 | date = March 2009 | pmid = 19255424 | pmc = 2657421 | doi = 10.1073/pnas.0808180106 | doi-access = free | bibcode = 2009PNAS..106.4453S }}</ref><ref>{{cite journal | vauthors = Scheer FA, Michelson AD, Frelinger AL, Evoniuk H, Kelly EE, McCarthy M, Doamekpor LA, Barnard MR, Shea SA | title = The human endogenous circadian system causes greatest platelet activation during the biological morning independent of behaviors | journal = PLOS ONE | volume = 6 | issue = 9 | pages = e24549 | date = 2011 | pmid = 21931750 | pmc = 3169622 | doi = 10.1371/journal.pone.0024549 | doi-access = free | bibcode = 2011PLoSO...624549S }}</ref> and by studying shift workers.<ref name="pubmed.ncbi.nlm.nih.gov"/><ref>{{cite journal | vauthors = Rabinovich-Nikitin I, Lieberman B, Martino TA, Kirshenbaum LA | title = Circadian-Regulated Cell Death in Cardiovascular Diseases | journal = Circulation | volume = 139 | issue = 7 | pages = 965–980 | date = February 2019 | pmid = 30742538 | doi = 10.1161/CIRCULATIONAHA.118.036550 | s2cid = 73436800 | doi-access = free }}</ref><ref name="Kervezee 396–412"/> Circadian misalignment is associated with many risk factors of cardiovascular disease. High levels of the atherosclerosis biomarker, resistin, have been reported in shift workers indicating the link between circadian misalignment and plaque build up in arteries.<ref name="Kervezee 396–412">{{cite journal | vauthors = Kervezee L, Kosmadopoulos A, Boivin DB | title = Metabolic and cardiovascular consequences of shift work: The role of circadian disruption and sleep disturbances | journal = The European Journal of Neuroscience | volume = 51 | issue = 1 | pages = 396–412 | date = January 2020 | pmid = 30357975 | doi = 10.1111/ejn.14216 | s2cid = 53031343 | url = https://escholarship.mcgill.ca/concern/articles/gt54kt25z }}</ref> Additionally, elevated triacylglyceride levels (molecules used to store excess fatty acids) were observed and contribute to the hardening of arteries, which is associated with cardiovascular diseases including heart attack, stroke and heart disease.<ref name="Kervezee 396–412"/><ref name="Proper e147–e157">{{cite journal | vauthors = Proper KI, van de Langenberg D, Rodenburg W, Vermeulen RC, van der Beek AJ, van Steeg H, van Kerkhof LW | title = The Relationship Between Shift Work and Metabolic Risk Factors: A Systematic Review of Longitudinal Studies | language = English | journal = American Journal of Preventive Medicine | volume = 50 | issue = 5 | pages = e147–e157 | date = May 2016 | pmid = 26810355 | doi = 10.1016/j.amepre.2015.11.013 | hdl = 1874/346787 | hdl-access = free }}</ref> Shift work and the resulting circadian misalignment is also associated with hypertension.<ref name="pmid22211891" />

==== Obesity and diabetes ====
[[Obesity]] and [[diabetes]] are associated with lifestyle and genetic factors. Among those factors, disruption of the circadian clockwork and/or misalignment of the circadian timing system with the external environment (e.g., light–dark cycle) can play a role in the development of metabolic disorders.<ref name="Zelinski2014" />

[[Shift work]] or chronic [[jet lag]] have profound consequences for circadian and metabolic events in the body. Animals that are forced to eat during their resting period show increased body mass and altered expression of clock and metabolic genes.<ref>{{cite journal | vauthors = Johnston JD | title = Physiological responses to food intake throughout the day | journal = Nutrition Research Reviews | volume = 27 | issue = 1 | pages = 107–18 | date = June 2014 | pmid = 24666537 | pmc = 4078443 | doi = 10.1017/S0954422414000055 }}</ref><ref name="Proper e147–e157"/> In humans, shift work that favours irregular eating times is associated with altered insulin sensitivity, diabetes and higher body mass.<ref name="pmid22211891">{{cite journal | vauthors = Delezie J, Challet E | title = Interactions between metabolism and circadian clocks: reciprocal disturbances | journal = Annals of the New York Academy of Sciences | volume = 1243 | issue = 1 | pages = 30–46 | date = December 2011 | pmid = 22211891 | doi = 10.1111/j.1749-6632.2011.06246.x | url = https://univoak.eu/islandora/object/islandora%3A64197/datastream/PDF/view | bibcode = 2011NYASA1243...30D | s2cid = 43621902 }} <!-- this is only a partial review --></ref><ref name="Proper e147–e157"/><ref>{{cite journal | vauthors = van Drongelen A, Boot CR, Merkus SL, Smid T, van der Beek AJ | title = The effects of shift work on body weight change - a systematic review of longitudinal studies | journal = Scandinavian Journal of Work, Environment & Health | volume = 37 | issue = 4 | pages = 263–275 | date = July 2011 | pmid = 21243319 | doi = 10.5271/sjweh.3143 | s2cid = 35457083 | doi-access = free }}</ref>

==== Cognitive effects ====
Reduced cognitive function has been associated with circadian misalignment. Chronic shift workers display increased rates of operational error, impaired visual-motor performance and processing efficacy which can lead to both a reduction in performance and potential safety issues.<ref>{{cite journal | vauthors = Chellappa SL, Morris CJ, Scheer FA | title = Effects of circadian misalignment on cognition in chronic shift workers | journal = Scientific Reports | volume = 9 | issue = 1 | pages = 699 | date = January 2019 | pmid = 30679522 | pmc = 6346005 | doi = 10.1038/s41598-018-36762-w | bibcode = 2019NatSR...9..699C }}</ref> Increased risk of dementia is associated with chronic night shift workers compared to day shift workers, particularly for individuals over 50 years old.<ref>{{cite journal | vauthors = Leng Y, Musiek ES, Hu K, Cappuccio FP, Yaffe K | title = Association between circadian rhythms and neurodegenerative diseases | journal = The Lancet. Neurology | volume = 18 | issue = 3 | pages = 307–318 | date = March 2019 | pmid = 30784558 | pmc = 6426656 | doi = 10.1016/S1474-4422(18)30461-7 }}</ref><ref>{{cite journal | vauthors = Wang ZZ, Sun Z, Zhang ML, Xiong K, Zhou F | title = Relationship between shift work, night work, and subsequent dementia: A systematic evaluation and meta-analysis | journal = Frontiers in Neurology | volume = 13 | pages = 997181 | date = 2022-11-07 | pmid = 36419534 | pmc = 9677942 | doi = 10.3389/fneur.2022.997181 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Leso V, Caturano A, Vetrani I, Iavicoli I | title = Shift or night shift work and dementia risk: a systematic review | journal = European Review for Medical and Pharmacological Sciences | volume = 25 | issue = 1 | pages = 222–232 | date = January 2021 | pmid = 33506911 | doi = 10.26355/eurrev_202101_24388 }}</ref>