The Circadian Timekeeping System As a Window into Neurodevelopmental Disorders

Sleep is a ubiquitous animal behavior that still remains a fundamental mystery. Among the least understood aspects of sleep is that its expression and architecture are highly regulated during animal development. Sleep is crucial for learning and memory, mood regulation, and metabolic health. It is not surprising then that sleep dysfunction is particularly common in children with neurodevelopmental disorders including autism spectrum disorders (ASD). Sleep is regulated by the combined influences of a homeostatic mechanism and the circadian clock. The clock is a multi-scaled biological timekeeping system that synchronizes gene expression, physiology, metabolism, and behavior with the 24 hour oscillations of the light/dark cycle.

There is an abundance of evidence from both the clinic and animal models that suggests a strong interplay between circadian rhythms and ASDs, however the mechanisms remain an area of active inquiry. I will review the molecular and cellular biology of the circadian clock and its links to animal and clinical models of ASD. I will review how the biology underlying syndromic disorders related to ASD such as Tuberous Sclerosis Complex, Fragile X Syndrome, and Angelman’s syndrome is intimately intertwined with circadian biology. I will suggest that many ASDs (and related disorders) are, at a fundamental level, ‘rhythm-opathies’.

The nexus between circadian clocks, sleep, and ASD is a new and important frontier that will lead to new targets and new therapies.