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The present study evaluated the daily urinary 6\u2010sulfatoxymelatonin (aMT6s) excretion profile and the salivary levels of tumor necrosis factor (TNF) and interleukin\u20106 (IL\u20106) in 20 controls and 20 ASD participants, as well as correlating these measures with sleep disturbances. Although 60% of ASD participants showed a significant night\u2010time rise in aMT6s excretion, this rise was significantly attenuated, compared to controls (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.05). The remaining 40% of ASD individuals showed no significant increase in nocturnal aMT6s. ASD individuals showed higher nocturnal levels of saliva TNF, but not IL\u20106. Dysfunction in the initiation and maintenance of sleep, as indicated by the Sleep Disturbance Scale for Children, correlated with night\u2010time aMT6s excretion (<jats:italic>r<\/jats:italic>\u00a0=\u00a0\u2212.28, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.05). Dysfunction in sleep breathing was inversely correlated with aMT6s (<jats:italic>r<\/jats:italic>\u00a0=\u00a0\u2212.31, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.05) and positively associated with TNF level (<jats:italic>r<\/jats:italic>\u00a0=\u00a0.42, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.01). Overall such data indicate immune\u2010pineal axis activation, with elevated TNF but not IL\u20106 levels associated with disrupted pineal melatonin release and sleep dysfunction in ASD. It is proposed that circadian dysregulation in ASD is intimately linked to heightened immune\u2010inflammatory activity. Such two\u2010way interactions of the immune\u2010pineal axis may underpin many aspects of ASD pathophysiology, including sleep disturbances, as well as cognitive and behavioral alterations.<\/jats:p>","DOI":"10.1111\/jpi.12715","type":"journal-article","created":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T20:17:10Z","timestamp":1610655430000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Disrupted nocturnal melatonin in autism: Association with tumor necrosis factor and sleep disturbances"],"prefix":"10.1111","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6937-7207","authenticated-orcid":false,"given":"Sanseray","family":"da Silveira Cruz\u2010Machado","sequence":"first","affiliation":[{"name":"Laboratory of Chronopharmacology Department of Physiology Institute of Biosciences University of S\u00e3o Paulo (USP) S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leila Maria","family":"Guissoni Campos","sequence":"additional","affiliation":[{"name":"Department of Anatomy School of Medicine University of Marilia (UNIMAR) Mar\u00edlia Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cintia Cristina","family":"Fadini","sequence":"additional","affiliation":[{"name":"Department of Speech, Language and Hearing Sciences S\u00e3o Paulo State University (UNESP) Marilia Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Anderson","sequence":"additional","affiliation":[{"name":"CRC Scotland &amp; 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