Sleep as a translationally-relevant endpoint in studies of autism spectrum disorder (ASD)

Abstract

Sleep has numerous advantages for aligning clinical and preclinical (basic neuroscience) studies of neuropsychiatric illness. Sleep has high translational relevance, because the same endpoints can be studied in humans and laboratory animals. In addition, sleep experiments are conducive to continuous data collection over long periods (hours/days/weeks) and can be based on highly objective neurophysiological measures. Here, we provide a translationally-oriented review on what is currently known about sleep in the context of autism spectrum disorder (ASD), including ASD-related conditions, thought to have genetic, environmental, or mixed etiologies. In humans, ASD is frequently associated with comorbid medical conditions including sleep disorders. Animal models used in the study of ASD frequently recapitulate dysregulation of sleep and biological (diurnal, circadian) rhythms, suggesting common pathophysiologies across species. As our understanding of the neurobiology of ASD and sleep each become more refined, it is conceivable that sleep-derived metrics may offer more powerful biomarkers of altered neurophysiology in ASD than the behavioral tests currently used in humans or lab animals. As such, the study of sleep in animal models for ASD may enable fundamentally new insights on the condition and represent a basis for strategies that enable the development of more effective therapeutics.

Fig. 1

Schematic of hypothesized etiology of sleep dysregulation in ASD. Sleep dysregulation may stem directly from the underlying pathology of ASD (a) and/or indirectly as the consequence of a bidirectional relationship with behavioral dysregulation (b)

Fig. 2

Sex differences and influence of body temperature and locomotor activity. Males have regular monophasic temperature oscillations, seen on example recordings from eight days (a), and averaged temperatures (b), that correspond to rhythms of locomotor activity (c). Due to the estrous cycle females have a four-day pattern of polyphasic oscillations during anestrus and a monophasic peak (E) that readily distinguishes the night of estrus (d, e). Locomotor activity is also selectively increased in estrus during the middle of the dark phase (f). Data from 5–6 C57BL/6J mice. **p < 0.01