Disrupted nocturnal melatonin in autism: Association with tumor necrosis factor and sleep disturbances

Author(s)

da Silveira Cruz-Machado, Sanseray ^[1] ; Guissoni Campos, Leila Maria ^[2] ; Fadini, Cintia Cristina ^[3] ; Anderson, George ^[4] ; Markus, Regina P. ^[1] ; Pinato, Luciana ^[3]

Affiliation

^[1] Univ Sao Paulo, Inst Biosci, Dept Physiol, Lab Chronopharmacol, Sao Paulo - Brazil

^[2] Univ Marilia UNIMAR, Sch Med, Dept Anat, Marilia, SP - Brazil

^[3] Sao Paulo State Univ UNESP, Dept Speech Language & Hearing Sci, BR-17525900 Marilia, SP - Brazil

^[4] CRC Scotland & London, London - England

• Document type: Journal article
• Source: Journal of Pineal Research; v. 70, n. 3 JAN 2021.
• Web of Science Citations: 3

Abstract

Sleep disturbances, abnormal melatonin secretion, and increased inflammation are aspects of autism spectrum disorder (ASD) pathophysiology. The present study evaluated the daily urinary 6-sulfatoxymelatonin (aMT6s) excretion profile and the salivary levels of tumor necrosis factor (TNF) and interleukin-6 (IL-6) 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-time rise in aMT6s excretion, this rise was significantly attenuated, compared to controls (P < .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-6. Dysfunction in the initiation and maintenance of sleep, as indicated by the Sleep Disturbance Scale for Children, correlated with night-time aMT6s excretion (r = -.28, P < .05). Dysfunction in sleep breathing was inversely correlated with aMT6s (r = -.31, P < .05) and positively associated with TNF level (r = .42, P < .01). Overall such data indicate immune-pineal axis activation, with elevated TNF but not IL-6 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-inflammatory activity. Such two-way interactions of the immune-pineal axis may underpin many aspects of ASD pathophysiology, including sleep disturbances, as well as cognitive and behavioral alterations. (AU)

• FAPESP's process: 15/04557-5 - The activation of immune-pineal axis by high-fat diet
• Grantee: Sanseray da Silveira Cruz Machado
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 11/15713-7 - Correlation between 6-sulphatoxymelatonin, sleep disorders and inflammatory cytokines in Autism Spectrum Disorder (ASD)
• Grantee: Cintia Cristina Fadini
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 11/51495-4 - Induction of melatonin synthesis by glia and neurons in injured central nervous system
• Grantee: Luciana Pinato
• Support Opportunities: Research Grants - Young Investigators Grants