Dysregulation of Circadian Rhythms in Autism Spectrum Disorders

Author(s)

Pinato, Luciana ^[1] ; Galina Spilla, Caio Sergio ^{[1, 2]} ; Markus, Regina Pekelmann ^[3] ; Cruz-Machado, Sanseray da Silveira ^[3]

Affiliation

^[1] Sao Paulo State Univ UNESP, Dept Speech Language & Hearing Sci, BR-17525900 Marilia, SP - Brazil

^[2] Univ Marilia UNIMAR, Sch Med, Dept Anat, BR-17525900 Marilia, SP - Brazil

^[3] Univ Sao Paulo, Inst Biosci, Dept Physiol, Lab Chronopharmacol, BR-05508090 Sao Paulo, SP - Brazil

• Document type: Review article
• Source: CURRENT PHARMACEUTICAL DESIGN; v. 25, n. 41, p. 4379-4393, 2019.
• Web of Science Citations: 1

Abstract

Background: The alterations in neurological and neumendocrine functions observed in the autism spectrum disorder (ASD) involves environmentally dependent dysregulation of neurodevelopment, in interaction with multiple coding gene defects. Disturbed sleep-wake patterns, as well as abnormal melatonin and glucocorticoid secretion, show the relevance of an underlying impairment of the circadian timing system to the behavioral phenotype of ASD. Thus, understanding the mechanisms involved in the circadian dysregulation in ASD could help to identify early biomarkers to improve the diagnosis and therapeutics as well as providing a significant impact on the lifelong prognosis. Objective: In this review, we discuss the organization of the circadian timing system and explore the connection between neuroanatomic, molecular, and neuroendocrine responses of ASD and its clinical manifestations. Here we propose interconnections between circadian dysregulation, inflammatory baseline and behavioral changes in ASD. Taking into account, the high relevancy of melatonin in orchestrating both circadian timing and the maintenance of physiological immune quiescence, we raise the hypothesis that melatonin or analogs should be considered as a pharmacological approach to suppress inflammation and circadian misalignment in ASD patients. Strategy: This review pmvides a comprehensive update on the state-of-art of studies related to inflammatory states and ASD with a special focus on the relationship with melatonin and clock genes. The hypothesis raised above was analyzed according to the published data. Conclusion: Current evidence supports the existence of associations between ASD to circadian dysregulation, behavior pmblems, increased inflammatory levels of cytokines, sleep disorders, as well as reduced circadian neuroendocrine responses. Indeed, major effects may be related to a low melatonin rhythm. We propose that maintaining the proper rhythm of the circadian timing system may be helpful to improve the health and to cope with several behavioral changes observed in ASD subjects. (AU)

• 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
• FAPESP's process: 13/13691-1 - Immune-pineal axis: time-niology integrated to surveillance and defense
• Grantee: Regina Pekelmann Markus
• Support Opportunities: Research Projects - Thematic Grants