Genetic Mechanisms Connecting Autism with Sleep & Circadian Rhythms

Sleep and circadian rhythm disorders are common in individuals with ASD. Disturbed sleep is shown to exacerbate core symptoms of ASD. Sleep problems may also intensify expression of other serious ASD comorbidities, such as epilepsy. Sleep has strong, neuronal-specific effects on the function of molecular, cellular and network mechanisms of neuronal plasticity. Further, studies in model systems indicate that sufficient sleep promotes proper neurodevelopment. In addition, mistimed sleep (i.e. mismatch between endogenous circadian rhythms and preferred sleep/wake schedule) is associated with a number of negative health outcomes and has been observed to disrupt physiological rhythms and circadian regulation of the transcriptome. Given the observations that disturbed sleep relates to more severe symptoms in ASD and that sleep is important to neuroplasticity, it is likely there is a crucial window during neurodevelopment where the quality of sleep has a lasting impact on neurological function. As such, the need for effective treatments for sleep disorders in ASD is profound. Understanding the causes and consequences of sleep disturbances in children with ASD is an important step toward mitigating these symptoms. It is possible that ASD symptoms drive disturbed sleep or that expression of ASD symptoms with comorbid sleep disturbances are modified by convergent genetic risk factors. Notably, the known biological functions for recurrently implicated genes in ASD suggest involvement of convergent molecular mechanisms. Evidence also indicates many of these convergent mechanisms overlap with those associated with risk for sleep disorders and expression of circadian rhythms. This suggests that pleiotropic genetic effects contribute to sleep and/or circadian disorders in some individuals with ASD. Understanding the genetic architecture underlying the relationship between ASD and expression of sleep and circadian disturbances may provide evidence useful toward optimizing more effective, personalized treatments in this population. This presentation will offer a broad overview of key findings from genetic studies of ASD, sleep traits, and circadian rhythm regulation highlighting shared genetic mechanisms that may underlie expression of sleep and circadian rhythm problems in ASD.