Understanding insomnia in autism spectrum disorder

Sleep problems in patients with autism spectrum disorder may be linked to a mutation in the gene Shank3 that in turn regulates the genes of the body’s 24-hour cycle.

Humans and mice with a mutation in the Shank3 gene have problems falling asleep. Image credit: Ashley Ingiosi (CC BY 4.0) with contribution from Eddy Van 3000 (CC BY-SA 2.0)

Autism spectrum disorder (ASD) is the most common neurodevelopmental disorder in the United States. People with ASD tend to have difficulties with communication and social interactions, restricted interests, and may repeat certain behaviors. They also often struggle to fall or stay asleep. Sleep deprivation may exacerbate other symptoms of the disorder. This makes life more difficult for both the person with ASD and their caregivers. Scientists do not yet know what causes sleep difficulties in people with ASD.

Unraveling the complex genetics that underlie ASD may help scientists better understand ASD-related sleep difficulties. One possible genetic culprit for sleep difficulties in ASD is a gene called SHANK3. Patients with an ASD-associated condition called Phelan-McDermid syndrome are often missing the SHANK3 gene. They also often have sleep problems.

Now, Ingiosi, Schoch et al. show that both patients with Phelan-McDermid syndrome and mice with a mutation in the Shank3 gene have problems falling asleep. Using a registry that collects genetic and sleep information on people with Phelan-McDermid syndrome, Ingiosi, Schoch et al. found that people who are missing SHANK3 frequently have trouble falling asleep and wake up many times each night. Mice missing part of the Shank3 gene also had difficulty falling asleep, even after they have been deprived of sleep.

Mice naturally have a daily pattern of sleep and activity. This 24-hour activity cycle is maintained by an internal circadian clock. In mice missing part of Shank3, the circadian clock genes are not turned on correctly. These genes were less active in mice missing Shank3, and this difference worsened with lack of sleep. These mice also ran less on a wheel than typical mice when kept in total darkness, even though the pattern of activity did not change. The experiments suggest that Shank3 controls sleep, likely through its effects on circadian clock genes. Learning more about what causes these sleep problems may help scientists develop ways to improve sleep in people with ASD and Phelan-McDermid syndrome.