Pharmacological Probing of Sleep Physiology in Autism

In the current project, we propose to modulate the neurotransmitter systems implicated in the sleep-wake balance and examine their impact on sleep physiology in autistic children and adolescents. The goal is to promote better sleep by either targeting wakefulness by using receptors antagonists such as diphenhydramine (anti-histaminergic) and suvorexant (DORA) or promoting sleepiness by using a receptor agonist, zolpidem (nonbenzodiazepine receptor agonist).  

We aim at investigating the target engagement of three sleep-inducing agents with different mechanisms on gold standard PSG, actigraphy, and circadian rhythm in children and adolescents with autism between the ages of 8 and 17 years. The rationale behind the use of diphenhydramine, zolpidem, and suvorexant is related to their distinct pharmacological profiles and their differential effect on the primary neurotransmitters involved in sleep. Diphenhydramine has significant antihistaminic activities and concurrent sedative properties. Zolpidem is a nonbenzodiazepine receptor agonist and is a hypnotic targeting sleep-onset or sleep maintenance. Suvorexant is a DORA and is prescribed to target insomnia characterized by difficulty with sleep onset and/or sleep maintenance. Our pharmacological probing study of sleep architecture will allow us to examine, for the first time, whether we can effectively modulate altered sleep parameters in autistic children and adolescents and examine their impact on sleep quality and clinical features.