Exploration and Evaluation of Core Circadian Rhythm Components in Relation to Autism Spectrum Disorders

Abstract

Autism spectrum disorders (ASDs) are a spectrum of neurodevelopmental disorders characterized by impaired social interaction and communication, as well as stereotyped and repetitive behaviors. ASDs affect nearly 2% of the United States child population and the worldwide prevalence has dramatically increased in recent years. The etiology is not clear but ASD is thought to be caused by a combination of intrinsic and extrinsic factors. Circadian rhythms are the ∼24 h rhythms driven by the endogenous biological clock, and they are found in a variety of physiological processes. Growing evidence from basic and clinical studies suggest that the dysfunction of the circadian timing system may be associated with ASD and its pathogenesis. Here I review the findings that link circadian dysfunctions to ASD in both experimental and clinical studies, then I report novel research furthering the relationship between the core circadian gene Bmal1 and ASD. I first introduce the organization of the circadian system and ASD. Next, I review physiological indicators of circadian rhythms that are found disrupted in ASD individuals, including sleep–wake cycles, melatonin, cortisol, and serotonin. I then review evidence in epidemiology, human genetics, and biochemistry that indicates underlying associations between circadian regulation and the pathogenesis of ASD. Finally, I design and report findings of my original basic research, including pervasive abnormalities in the developing mouse cerebellum and social deficits as a result of deletion of the core circadian component Bmal1. In conclusion, I propose that understanding the functional importance of the circadian clock in normal and aberrant neurodevelopmental processes may provide a novel perspective to tackle ASD, and clinical treatments for ASD individuals should comprise an integrative approach considering the dynamics of daily rhythms in physical, mental, and social processes.