- Awarded: 2021
- Award Type: Pilot
- Award #: 878115
Sleep problems occur at a higher rate in people with autism spectrum disorder (ASD), affecting up to 93 percent of people with ASD. Three key features characterize ASD sleep problems: significant delays falling asleep, multiple night awakenings and overall less sleep. These defining features of insomnia predict the severity of core diagnostic features of ASD and get worse with age, heavily affecting the quality of life of individuals and caregivers. In addition, problems falling asleep in the first year of life often precede an autism diagnosis and are associated with altered patterns of brain development. However, the developmental trajectory of sleep problems in ASD remains largely unexplored.
Lucia Peixoto’s central hypothesis is that sleep and circadian rhythm changes in ASD can be detected early in life, worsen with age and share a common mechanism despite ASD heterogeneity. Sleep is extremely evolutionarily conserved. Therefore, animal studies have the potential to provide great insight that can be readily translatable to individuals with ASD, such as pinpointing important developmental timepoints as well as potential mechanisms underlying sleep and arousal problems, which can inform future studies and interventions in clinical populations.
To test this hypothesis, Peixoto’s lab plans to use mouse models of three monogenic syndromes with a high rate of ASD diagnosis that also have a high prevalence of insomnia: Shank3ΔC mice (Phelan-McDermid syndrome), Mecp2 null mice (Rett syndrome) and Ube3am-/p+ (Angelman syndrome). The Peixoto lab has already shown that Shank3ΔC adult mice recapitulate aspects of the autism insomnia phenotype, as well as dysregulation of circadian transcription factors1. Building upon their recent studies1,2, they will evaluate circadian rhythms and sleep in the presence and absence of light, under baseline conditions and following sleep deprivation as well as across postnatal development.
These studies will allow Peixoto’s lab to, in the future, leverage several models to understand molecular mechanisms underlying causes and consequences of insomnia in ASD. This will also lead to a better understanding of the interaction between sleep, circadian rhythms and brain development.