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 nighttime rise in aMT6s excretion, this rise was significantly attenuated, compared to controls (p<0.05). 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 nighttime aMT6s excretion (r=-0.28, p<0.05). Dysfunction in sleep breathing was inversely correlated to aMT6s (r=-0.31, p<0.05) and positively associated with TNF level (r=0.42, p<0.01). 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.This article is protected by copyright. All rights reserved.
About The Expert
Sanseray da Silveira Cruz-Machado
Leila Maria Guissoni Campos
Cintia Cristina Fadini
George Anderson
Regina P Markus
Luciana Pinato
References
PubMed