Sleep deprivation in early life increases autism risk

It has long been proven that sleep deprivation in adults causes long-term mental and physical health problems, including, but not limited to, a weakened immune system, weight gain, depression and an increased risk of dementia.

But why does lack of sleep have such serious consequences?

Sleep actually plays a crucial role from the moment we are born. As babies, our brains are still forming the ends of neurons called synapses, which are important in learning, attention, working memory and long-term memory. Sleep allows these neurons to develop and connect, building brain functions for the rest of life.

If this delicate but important process were disrupted by constant wakefulness or separation anxiety, it could have lasting effects on the brain and behavior.

Now, a new study led by Sean Gay, a graduate student in the laboratory of Graham Diering, PhD, assistant professor in the Department of Cell Biology and Physiology at the UNC School of Medicine, has given us more insight into how sleep loss during early periods of sleep occur. life affects key parts of brain development – ​​and how this can also increase the risk of developing autism spectrum disorder (ASD). Their findings were published in the Proceedings of the National Academy of Sciences.

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

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

Sleep disorders and autism

Sleep problems are an important early indicator of brain growth problems and other neurodevelopmental disorders, such as ASD, attention deficit hyperactivity disorder, and intellectual disability. Sleep disruption has been observed in >80% of people with ASD, but whether sleep disruption is a cause or consequence of ASD is largely unknown.

Diering has long studied how sleep strengthens synapses over time – a process called synaptic plasticity – and how a lack of sleep can contribute to cognitive and neurodegenerative disorders. Better understanding the links between sleep and ASD could also help researchers and clinicians make earlier diagnoses and devise new treatment strategies for the disorder.

In 2022, the Diering lab sought to understand whether sleep disruption during early life could interact with the underlying genetic risk for ASD to cause long-lasting changes in adult behavior. Using mouse models, researchers found that sleep disruption during the third week of life (similar to ages 1-2 years in humans) caused long-lasting deficits in social behavior in male mice that were genetically vulnerable to having ASD.

A study of sleep recovery

The Diering lab wanted to explore these findings further, this time with a dive into how adult and developing mouse models compensate for sleep loss. Using specialized mouse houses with highly sensitive sensors, researchers were able to carefully monitor mouse movements and breathing, allowing the researchers to keep score of waking and sleeping states.

Researchers showed that when the adult mouse models lost a significant amount of sleep, they compensated by increasing sleep later during their normal active hours. This response, also called ‘sleep recovery’, allowed the adults to ‘catch up’ on lost sleep.

The younger mice; on the other hand, sleep recovery was completely lacking. This confirmed the researcher’s hypothesis that the younger mice may be more sensitive to the harmful effects of sleep deprivation. Researchers also noted that sleep deprivation in young mice completely impaired their performance on a learning memory task, while adults were much more resilient after sleep loss.

The lab then turned its attention to the effects of sleep and sleep deprivation on neuronal synapses, which mediate communication between neurons and are the main location for memory formation and storage. They are also well studied for their crucial role in promoting sleep health.

Researchers conducted a number of molecular analyzes to see how sleep deprivation affects synapses. Using advanced protein analyses, they were able to map the protein composition and biochemical changes that affect synapses. The analysis showed that sleep deprivation in young mice, but not adults, strongly affected the formation of synapses, an important aspect of brain development.

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

Future treatment options for autism

An ongoing mission of the laboratory, based on the molecular work of this current study, is to develop next-generation sleep-based medications that can be used in children. Rather than acting as a sedative, they hope to create a drug that can target synapses to restore sleep function, rather than changing sleep behavior itself.

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