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Besedovsky L, Lange T, Haack M. The sleep-immune crosstalk in health and disease. Physiol Rev. 2019;99:1325–80. https://doi.org/10.1152/physrev.00010.2018.
Ditmer M, Gabryelska A, Turkiewicz S, Białasiewicz P, Małecka-wojciesko E, Sochal M. Sleep problems in chronic inflammatory diseases: Prevalence, Treatment, and new perspectives. Narrative Rev J Clin Med. 2022;11.
Kadier K, Dilixiati D, Ainiwaer A, Liu X, Lu J, Liu P, et al. Analysis of the relationship between sleep-related disorder and systemic immune-inflammation index in the US population. BMC Psychiatry. 2023;23:773. https://doi.org/10.1186/s12888-023-05286-7.
Krueger JM, Obál F, Fang J, Kubota T, Taishi P. The role of cytokines in physiological sleep regulation. Ann N Y Acad Sci. 2001;933:211–21. https://doi.org/10.1111/j.1749-6632.2001.tb05826.x.
Lasselin J, Ingre M, Regenbogen C, Olsson MJ, Garke M, Brytting M, et al. Sleep during naturally occurring respiratory infections: a pilot study. Brain Behav Immun. 2019;79:236–43. https://doi.org/10.1016/j.bbi.2019.02.006.
Sharpley AL, Cooper CM, Williams C, Godlewska BR, Cowen PJ. Effects of typhoid vaccine on inflammation and sleep in healthy participants: a double-blind, placebo-controlled, crossover study. Psychopharmacology. 2016;233:3429–35. https://doi.org/10.1007/s00213-016-4381-z.
Bryant PA, Trinder J, Curtis N. Sick and tired: does sleep have a vital role in the immune system? Nat Rev Immunol. 2004. https://doi.org/10.1038/nri1369.
Involvement of cytokines in slow wave sleep. Progress in brain research. Elsevier; 2011. p. 39–47. https://doi.org/10.1016/b978-0-444-53839-0.00003-x.
Taishi P, Chen Z, Obál F, Hansen MK, Zhang J, Fang J, et al. Sleep-associated changes in interleukin-1β mRNA in the brain. J Interferon Cytokine Res. 1998;18:793–8. https://doi.org/10.1089/jir.1998.18.793.
Zielinski MR, Kim Y, Karpova SA, McCarley RW, Strecker RE, Gerashchenko D. Chronic sleep restriction elevates brain interleukin-1 beta and tumor necrosis factor-alpha and attenuates brain-derived neurotrophic factor expression. Neurosci Lett. 2014;580:27–31. https://doi.org/10.1016/j.neulet.2014.07.043.
Zielinski MR, Krueger JM. Sleep and innate immunity. Front Bioscience – Scholar. 2011;3:632–42. https://doi.org/10.2741/s176.
Xie Y, Ba L, Wang M, Deng SY, Chen SM, Huang LF, et al. Chronic sleep fragmentation shares similar pathogenesis with neurodegenerative diseases: endosome-autophagosome-lysosome pathway dysfunction and microglia-mediated neuroinflammation. CNS Neurosci Ther. 2020;26:215–27. https://doi.org/10.1111/cns.13218.
De Picker LJ, Morrens M, Branchi I, Haarman BCM, Terada T, Kang MS, et al. TSPO PET brain inflammation imaging: a transdiagnostic systematic review and meta-analysis of 156 case-control studies. Brain Behav Immun. 2023;113:415–31. https://doi.org/10.1016/j.bbi.2023.07.023.
Jain P, Chaney AM, Carlson ML, Jackson IM, Rao A, James ML. Neuroinflammation PET imaging: current opinion and future directions. J Nucl Med. 2020;61:1107–12. https://doi.org/10.2967/jnumed.119.229443.
Nutma E, Fancy N, Weinert M, Tsartsalis S, Marzin MC, Muirhead RCJ, et al. Translocator protein is a marker of activated microglia in rodent models but not human neurodegenerative diseases. Nat Commun. 2023;14:5247. https://doi.org/10.1038/s41467-023-40937-z.
Gao C, Jiang J, Tan Y, Chen S. Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets. Sig Transduct Target Ther. 2023;8:359. https://doi.org/10.1038/s41392-023-01588-0.
Ekblad LL, Tuisku J, Koivumäki M, Helin S, Rinne JO, Snellman A. Insulin resistance and body mass index are associated with TSPO PET in cognitively unimpaired elderly. J Cereb Blood Flow Metab. 2023;43:1588–600. https://doi.org/10.1177/0271678X231172519.
Tuisku J, Plavén-Sigray P, Gaiser EC, Airas L, Al-Abdulrasul H, Brück A, et al. Effects of age, BMI and sex on the glial cell marker TSPO — a multicentre [11 C]PBR28 HRRT PET study. Eur J Nucl Med Mol Imaging. 2019;46(11):2329–38. https://doi.org/10.1007/s00259-019-04403-7.
Tamm S, Cervenka S, Forsberg A, Estelius J, Grunewald J, Gyllfors P, et al. Evidence of fatigue, disordered sleep and peripheral inflammation, but not increased brain TSPO expression, in seasonal allergy: a [ 11 C]pbr28 PET study. Brain Behav Immun. 2018;68:146–57. https://doi.org/10.1016/j.bbi.2017.10.013.
Tamm S, Lensmar C, Andreasson A, Axelsson J, Morén AF, Grunewald J, et al. Objective and subjective sleep in rheumatoid arthritis and severe seasonal allergy: preliminary assessments of the role of sickness, central and peripheral inflammation. Nat Sci Sleep. 2021;13:775–89. https://doi.org/10.2147/NSS.S297702.
Buysse DJ. Sleep health: can we define it? Does it matter? Sleep. 2014;37:9–17. https://doi.org/10.5665/sleep.3298.
Axelsson J, Van Someren EJW, Balter LJT. Sleep profiles of different psychiatric traits. Transl Psychiatry. 2024;14:284. https://doi.org/10.1038/s41398-024-03009-4.
Kwok CS, Kontopantelis E, Kuligowski G, Gray M, Muhyaldeen A, Gale CP, et al. Self-reported sleep duration and quality and cardiovascular disease and mortality: a dose‐response meta-analysis. JAHA. 2018;7:e008552. https://doi.org/10.1161/JAHA.118.008552.
Roenneberg T. How can social jetlag affect health? Nat Rev Endocrinol. 2023;19:383–4. https://doi.org/10.1038/s41574-023-00851-2.
Matricciani L, Bin YS, Lallukka T, Kronholm E, Wake M, Paquet C, et al. Rethinking the sleep-health link. Sleep Health. 2018;4:339–48. https://doi.org/10.1016/j.sleh.2018.05.004.
Girtman KL, Baylin A, O’Brien LM, Jansen EC. Later sleep timing and social jetlag are related to increased inflammation in a population with a high proportion of OSA: findings from the Cleveland family study. J Clin Sleep Med. 2022;18:2179–87. https://doi.org/10.5664/jcsm.10078.
Thompson C, Legault J, Moullec G, Baltzan M, Cross N, Dang-Vu TT, et al. A portrait of obstructive sleep apnea risk factors in 27,210 middle-aged and older adults in the Canadian longitudinal study on aging. Sci Rep. 2022;12:5127. https://doi.org/10.1038/s41598-022-08164-6.
Irwin MR, Olmstead R, Carroll JE. Sleep disturbance, sleep duration, and inflammation: a systematic review and meta-analysis of cohort studies and experimental sleep deprivation. Biol Psychiatry. 2016;80:40–52. https://doi.org/10.1016/j.biopsych.2015.05.014.
Mullington JM, Simpson NS, Meier-Ewert HK, Haack M. Sleep loss and inflammation. Best Pract Res Clin Endocrinol Metab. 2010;24:775–84. https://doi.org/10.1016/j.beem.2010.08.014.
Ballesio A, Fiori V, Lombardo C. Effects of experimental sleep deprivation on peripheral inflammation: an updated meta-analysis of human studies. Advance online publication. J Sleep Res. 2025:e70099. https://doi.org/10.1111/jsr.70099.
Aho V, Ollila HM, Kronholm E, Bondia-Pons I, Soininen P, Kangas AJ, et al. Prolonged sleep restriction induces changes in pathways involved in cholesterol metabolism and inflammatory responses. Sci Rep. 2016;6:24828. https://doi.org/10.1038/srep24828.
Bakour C, Schwartz S, O’Rourke K, Wang W, Sappenfield W, Couluris M, et al. Sleep duration trajectories and systemic inflammation in young adults: results from the National longitudinal study of adolescent to adult health (Add health). Sleep. 2017;40. https://doi.org/10.1093/sleep/zsx156.
Ferrie JE, Kivimaki M, Akbaraly TN, Singh-Manoux A, Miller MA, Gimeno D, et al. Associations between change in sleep duration and inflammation: findings on C-reactive protein and Interleukin 6 in the Whitehall II study. Am J Epidemiol. 2013;178:956–61. https://doi.org/10.1093/aje/kwt072.
Huang L, Long Z, Lyu J, Chen Y, Li R, Wang Y, et al. The associations of trajectory of sleep duration and inflammation with hypertension: a longitudinal study in China. NSS. 2021;13:1797–806. https://doi.org/10.2147/NSS.S329038.
Gustavsson J, Papenberg G, Falahati F, Laukka EJ, Kalpouzos G. Contributions of the catechol-O-methyltransferase Val158Met polymorphism to changes in brain iron across adulthood and their relationships to working memory. Front Hum Neurosci. 2022;16:838228. https://doi.org/10.3389/fnhum.2022.838228.
Sørensen C, Dudka I, Virel A, Kåreholt I, Balter LJt, Axelsson J, et al. Sleep health associations with serum metabolites in healthy adults. Brain Behav Immun. 2025;48:101050. https://doi.org/10.1016/j.bbih.2025.101050.
Owen DR, Yeo AJ, Gunn RN, Song K, Wadsworth G, Lewis A, et al. An 18-kDa translocator protein (TSPO) polymorphism explains differences in binding affinity of the PET radioligand PBR28. J Cereb Blood Flow Metab. 2012;32:1–5. https://doi.org/10.1038/jcbfm.2011.147.
Collste K, Forsberg A, Varrone A, Amini N, Aeinehband S, Yakushev I, et al. Test–retest reproducibility of [11 C]PBR28 binding to TSPO in healthy control subjects. Eur J Nucl Med Mol Imaging. 2016;43:173–83. https://doi.org/10.1007/s00259-015-3149-8.
Nordin M, Åkerstedt T, Nordin S. Psychometric evaluation and normative data for the Karolinska sleep questionnaire. Sleep Biol Rhythms. 2013;11:216–26. https://doi.org/10.1111/sbr.12024.
Kreisl WC, Jenko KJ, Hines CS, Hyoung Lyoo C, Corona W, Morse CL, et al. A genetic polymorphism for translocator protein 18 kDa affects both in vitro and in vivo radioligand binding in human brain to this putative biomarker of neuroinflammation. J Cereb Blood Flow Metab. 2013;33(1):53–8. https://doi.org/10.1038/jcbfm.2012.131.
Bates D, Mächler M, Bolker BM, Walker SC. Fitting linear mixed-effects models using lme4. J Stat Softw. 2015;67:1–48. https://doi.org/10.18637/jss.v067.i01.
Andreasson A, Axelsson J, Bosch JA, Balter LJ. Poor sleep quality is associated with worse self-rated health in long sleep duration but not short sleep duration. Sleep Med. 2021;88:262–6. https://doi.org/10.1016/j.sleep.2021.10.028.
Yin J, Jin X, Shan Z, Li S, Huang H, Li P, et al. Relationship of sleep duration with all-cause mortality and cardiovascular events: a systematic review and dose-response meta-analysis of prospective cohort studies. J Am Heart Assoc. 2017;6:e005947. https://doi.org/10.1161/JAHA.117.005947.
Hirshkowitz M, Whiton K, Albert SM, Alessi C, Bruni O, DonCarlos L, et al. National sleep foundation’s updated sleep duration recommendations: final report. Sleep Health. 2015;1:233–43. https://doi.org/10.1016/j.sleh.2015.10.004.
Pilcher JJ, Ginter DR, Sadowsky B. Sleep quality versus sleep quantity: relationships between sleep and measures of health, well-being and sleepiness in college students. J Psychosom Res. 1997;42:583–96. https://doi.org/10.1016/S0022-3999(97)00004-4.
Kalmbach DA, Anderson JR, Drake CL. The impact of stress on sleep: pathogenic sleep reactivity as a vulnerability to insomnia and circadian disorders. J Sleep Res. 2018;27:e12710. https://doi.org/10.1111/jsr.12710.
Grandner MA, Drummond SPA. Who are the long sleepers? Towards an understanding of the mortality relationship. Sleep Med Rev. 2007;11:341–60. https://doi.org/10.1016/j.smrv.2007.03.010.
Xu W, Tan L, Su B, Yu H, Bi Y, Yue X, et al. Sleep characteristics and cerebrospinal fluid biomarkers of Alzheimer’s disease pathology in cognitively intact older adults: the CABLE study. Alzheimers Dement. 2020;16:1146–52. https://doi.org/10.1002/alz.12117.
Stolicyn A, Lyall LM, Lyall DM, Høier NK, Adams MJ, Shen X, et al. Comprehensive assessment of sleep duration, insomnia, and brain structure within the UK biobank cohort. Sleep. 2024;47:zsad274. https://doi.org/10.1093/sleep/zsad274.
Wang M, Yang M, Liang S, Wang N, Wang Y, Sambou ML, et al. Association between sleep traits and biological aging risk: a Mendelian randomization study based on 157 227 cases and 179 332 controls. Sleep. 2024;47:zsad299. https://doi.org/10.1093/sleep/zsad299.
López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. Hallmarks of aging: an expanding universe. Cell. 2023;186:243–78. https://doi.org/10.1016/j.cell.2022.11.001.
Sandiego CM, Gallezot JD, Pittman B, Nabulsi N, Lim K, Lin SF, et al. Imaging robust microglial activation after lipopolysaccharide administration in humans with PET. Proc Natl Acad Sci U S A. 2015;112:12468–73. https://doi.org/10.1073/pnas.1511003112.
Nettis MA, Veronese M, Nikkheslat N, Mariani N, Lombardo G, Sforzini L, et al. PET imaging shows no changes in TSPO brain density after IFN-α immune challenge in healthy human volunteers. Transl Psychiatry. 2020;10:89. https://doi.org/10.1038/s41398-020-0768-z.
Hannestad J, DellaGioia N, Gallezot J-D, Lim K, Nabulsi N, Esterlis I, et al. The neuroinflammation marker translocator protein is not elevated in individuals with mild-to-moderate depression: a [11C]PBR28 PET study. Brain Behav Immun. 2013;33:131–8. https://doi.org/10.1016/j.bbi.2013.06.010.
Cisbani G, Koppel A, Knezevic D, Suridjan I, Mizrahi R, Bazinet RP. Peripheral cytokine and fatty acid associations with neuroinflammation in AD and aMCI patients: An exploratory study. Brain Behav Immun. 2020;87:679–88. https://doi.org/10.1016/j.bbi.2020.02.014.
Turkheimer FE, Althubaity N, Schubert J, Nettis MA, Cousins O, Dima D, et al. Increased serum peripheral C-reactive protein is associated with reduced brain barriers permeability of TSPO radioligands in healthy volunteers and depressed patients: implications for inflammation and depression. Brain Behav Immun. 2021;91:487–97. https://doi.org/10.1016/j.bbi.2020.10.025.
Kayser KC, Puig VA, Estepp JR. Predicting and mitigating fatigue effects due to sleep deprivation: a review. Front Neurosci. 2022;16:930280. https://doi.org/10.3389/fnins.2022.930280.
Yao F, Zhao J, Cui Y, Yu D, Tang X. Daytime sleep as compensation for the effects of reduced nocturnal sleep on the incidence of hypertension: a cohort study. NSS. 2021;13:1061–74. https://doi.org/10.2147/NSS.S316113.
Petruo VA, Mückschel M, Beste C. On the role of the prefrontal cortex in fatigue effects on cognitive flexibility – a system neurophysiological approach. Sci Rep. 2018;8:6395. https://doi.org/10.1038/s41598-018-24834-w.
De La Vega A, Chang LJ, Banich MT, Wager TD, Yarkoni T. Large-scale meta-analysis of human medial frontal cortex reveals tripartite functional organization. J Neurosci. 2016;36:6553–62. https://doi.org/10.1523/JNEUROSCI.4402-15.2016.
Westwood AJ, Beiser A, Jain N, Himali JJ, DeCarli C, Auerbach SH, et al. Prolonged sleep duration as a marker of early neurodegeneration predicting incident dementia. Neurology. 2017;88:1172–9. https://doi.org/10.1212/WNL.0000000000003732.
Sako W, Murakami N, Izumi Y, Kaji R. The difference in putamen volume between MSA and PD: evidence from a meta-analysis. Parkinsonism Relat Disord. 2014;20:873–7. https://doi.org/10.1016/j.parkreldis.2014.04.028.
Zhang P-F, Gao F. Neuroinflammation in Parkinson’s disease: a meta-analysis of PET imaging studies. J Neurol. 2022;269:2304–14. https://doi.org/10.1007/s00415-021-10877-z.
Chen Y, Gao Y, Sun X, Wang BH, Qin L, Wu IX, et al. Association between sleep factors and Parkinson’s disease: a prospective study based on 409,923 UK biobank participants. Neuroepidemiology. 2023;57:293–303. https://doi.org/10.1159/000530982.
Stock AA, Lee S, Nahmod NG, Chang A-M. Effects of sleep extension on sleep duration, sleepiness, and blood pressure in college students. Sleep Health. 2020;6:32–9. https://doi.org/10.1016/j.sleh.2019.10.003.
Stranges S, Dorn JM, Shipley MJ, Kandala NB, Trevisan M, Miller MA, et al. Correlates of short and long sleep duration: a cross-cultural comparison between the United Kingdom and the United States: the Whitehall II study and the Western New York health study. Am J Epidemiol. 2008;168:1353–64. https://doi.org/10.1093/aje/kwn337.
Cheng X, Wei Y, Wang R, Jia C, Zhang Z, An J, et al. Associations of essential trace elements with epigenetic aging indicators and the potential mediating role of inflammation. Redox Biol. 2023;67:102910. https://doi.org/10.1016/j.redox.2023.102910.
Xie L, Kang H, Xu Q, Chen MJ, Liao Y, Thiyagarajan M, et al. Sleep drives metabolite clearance from the adult brain. Science. 2013;342:373–7. https://doi.org/10.1126/science.1241224.
Miao A, Luo T, Hsieh B, Edge CJ, Gridley M, Wong RTC, et al. Brain clearance is reduced during sleep and anesthesia. Nat Neurosci. 2024;27:1046–50. https://doi.org/10.1038/s41593-024-01638-y.
Diering GH, Nirujogi RS, Roth RH, Worley PF, Pandey A, Huganir RL. Homer1a drives homeostatic scaling-down of excitatory synapses during sleep. Science. 2017;355:511–5. https://doi.org/10.1126/science.aai8355.
Tononi G, Cirelli C. Sleep and the price of plasticity: from synaptic and cellular homeostasis to memory consolidation and integration. Neuron. 2014;81:12–34. https://doi.org/10.1016/j.neuron.2013.12.025.
Garbarino S, Lanteri P, Bragazzi NL, Magnavita N, Scoditti E. Role of sleep deprivation in immune-related disease risk and outcomes. Commun Biol. 2021;4:1304. https://doi.org/10.1038/s42003-021-02825-4.
Cotter D, Mackay D, Landau S, Kerwin R, Everall I. Reduced glial cell density and neuronal size in the anterior cingulate cortex in major depressive disorder. Arch Gen Psychiatry. 2001;58:545. https://doi.org/10.1001/archpsyc.58.6.545.
Rodríguez JJ, Witton J, Olabarria M, Noristani HN, Verkhratsky A. Increase in the density of resting microglia precedes neuritic plaque formation and microglial activation in a transgenic model of Alzheimer’s disease. Cell Death Dis 2010;1:e1–e1. https://doi.org/10.1038/cddis.2009.2