Systematic review of sleep disturbances and circadian sleep desynchronization in autism spectrum disorder: toward an integrative model of a self-reinforcing loop

Abstract

Background: A compelling number of studies, conducted in both children and adults, have reported an association between sleep disturbances/circadian sleep alterations and Autism Spectrum Disorder (ASD); however, the data are sparse and the nature of this link is still unclear. The present review aimed to systematically collect the literature data relevant on sleep disturbances and circadian sleep dysrhythmicity related to ASD across all ages and to provide an integrative theoretical frameworks of their association. Methods: A systematic review of the MEDLINE, PubMed and Cochrane databases was conducted from November 2018 to February 2019.The search strategies used were MeSH headings and keywords for “sleep-wake circadian rhythms” OR “circadian sleep disorders” OR “sleep-wake pattern” OR “sleep disorders” OR “melatonin” AND “autism spectrum disorder” OR “autism”. Results: One-hundred and three studies were identified, 15 regarded circadian sleep dysrhythmicity, 74 sleep disturbances and 17 melatonin alterations in children and adults with ASD. Our findings suggested that autistic subjects frequently present sleep disturbances in particular short sleep duration, low sleep quality/efficiency and circadian sleep desynchronization such as delayed phases and/or eveningness. Sleep disturbances and circadian sleep alterations have been related to the severity of autistic symptoms. Genetic studies have shown polymorphisms in circadian CLOCK genes and in genes involved in melatonin pathways in subjects with ASD. Conclusions: Sleep disturbances and circadian sleep alterations are frequent in subjects with autistic symptoms who have shown polymorphisms in clock genes expression and in genes involved in melatonin production. The impairment of circadian sleep regulation may increase the individual's vulnerability to develop symptoms of autism spectrum disorder by altering the sleep regulation in toto which play a key role in brain development. Even though controversies and “research gaps “ are present in literature at this point, we may hypothesize a bidirectional relation between circadian sleep dysfunction and ASD. In particular circadian sleep dysrythmicity may predispose to develop ASD symptoms and vice-versa within a self-reinforcing feedback loop. By targeting sleep disturbances and circadian sleep dysrhythmicity we may improve treatment strategies for both children and adults with ASD