Autism Risk Increased due to Sleep Deprivation

Autism caused due to sleep deprivation in adults has long been shown to create long-term mental and physical health problems, such as reduced immune systems, weight gain, depression, and an increased risk of dementia.

But why can a lack of sleep have such severe consequences?

Sleep plays an important function from the minute we are born. As babies, our brains are still developing the terminals of neurons known as synapses, which play crucial roles in learning, attention, working memory, and long-term memory. Sleep permits these neurons to mature and connect, establishing brain functions for the rest of life.

If this delicate but vital process is disturbed, whether by continual waking or separation anxiety, it may have long-term repercussions on the brain and behavior.

Now, a new study led by Sean Gay, a graduate student in Graham Diering’s lab, PhD, assistant professor in the Department of Cell Biology and Physiology at the UNC School of Medicine, has shed more light on how sleep deprivation during early life affects key aspects of brain development – and how it can increase one’s risk of developing autism spectrum disorder. The results were published in the Proceedings of the National Academy of Sciences.

The unique effects of sleep loss during development are largely unexplored. Our data show that babies and children are more vulnerable to the negative effects of sleep disruption. We also found that sleep loss during this crucial period of time can negatively interact with underlying genetic risk for autism spectrum disorder.”

Graham Diering, PhD, Assistant Professor, Department of Cell Biology and Physiology, UNC School of Medicine

Sleep interruption and autism

Sleep problems are an important early indicator of brain growth issues and other neurodevelopmental disorders like ASD, ADHD, and intellectual disability. Sleep disturbance has been observed in more than 80% of persons with ASD, however it is unclear whether this is a cause or a result of ASD.

Diering has long investigated how sleep strengthens synapses over time, a process known as synaptic plasticity, and how a lack of sleep might lead to cognitive and neurodegenerative problems. If researchers could better understand the links between sleep and ASD, they could make earlier diagnoses and develop new treatment options.

In 2022, the Diering lab intended to determine whether sleep disruption during early life could interact with underlying genetic risk for ASD to generate long-term effects in adult behavior. Using mouse models, researchers discovered that sleep disturbance during the third week of life (equivalent to age 1-2 in humans) resulted in long-term abnormalities in social behavior in male mice who were genetically predisposed to ASD.

A study on sleep rebound

The Diering lab decided to investigate these findings further, this time focusing on how adult and developing mouse models compensate for sleep loss. Using sophisticated mouse housing with incredibly sensitive sensors, researchers were able to closely observe mouse movements and respiration, allowing them to keep track of wake and sleep times.

Researchers discovered that when adult mouse models lost a large quantity of sleep, they compensated by getting more sleep later during their typical active hours. This “sleep rebound” response allows people to “make up” for lost sleep.

The younger mice, on the other hand, which lacked sleep, recovered completely. This supported the researchers’ hypothesis that younger mice may be more vulnerable to the negative effects of sleep deprivation. Researchers also discovered that sleep deprivation completely harmed young mice’s performance in a learning memory challenge, whereas adults were significantly more resilient following sleep loss.

The team then focused on the effects of sleep and sleep deprivation on neuronal synapses, which facilitate communication between neurons and serve as the primary site for memory creation and storage. They are also well-studied for their important function in improving sleep quality.

Researchers conducted a series of molecular assays to investigate how sleep deprivation impacts synapses. Using advanced protein analysis, they were able to pinpoint the protein composition and molecular changes that alter synapses. The study found that sleep deprivation had a significant impact on synapse formation, a critical part of brain development, in young mice but not in adults.

“This now provides one of the largest and most comprehensive datasets to examine the molecular effects of sleep loss across the lifespan,” said Diering.

Future therapeutic options for autism.
The lab’s ongoing objective, as informed by the molecular work of this current study, is to produce next-generation sleep-based therapies for use in children. Instead of functioning as a sedative, they seek to develop a medication that can target synapses and restore sleep function, rather than changing sleep behavior.

“Development is not something that one can go back and do again,” said Diering. “Sleep is important for the entire life and especially during development. Understanding what we know now will place greater emphasis on understanding sleep issues in ASD and could lead to an important therapeutic avenue to treat ASD and other developmental conditions.”

For more information: Gay, S. M., et al. (2024) Developing forebrain synapses are uniquely vulnerable to sleep loss. Proceedings of the National Academy of Sciences. doi.org/10.1073/pnas.2407533121.