• Posted January 4, 2024

Brain's 'Spaces' Hold Clues to Origins of Autism

The fluid-filled spaces around the brain's blood vessels need proper waste "clearance" every few hours. When that fails to happen, a baby's risk for autism appears to rise, new research shows.

It's too early to say that trouble within these "perivascular" spaces causes autism, but it seems to be an early marker for the condition, a team from the University of North Carolina (UNC) reports.

“Our findings were striking, given that neuro-radiologists typically view enlarged perivascular spaces as a sign of neuro-degeneration in adults, but this study reported it in toddlers,” noted study co-author Dea Garic, a research assistant professor in UNC's department of psychiatry.

“This is an important aspect of brain development in the first years of life that should be monitored," Garic added in a university news release.

The findings were published recently in the journal JAMA Network Open.

According to Autism Speaks, about 1 in every 36 U.S. children is diagnosed with an autism spectrum disorder. Autism's exact origins remain unclear, and a better understanding of the condition could lead to better prevention and treatment.

In the new study, the UNC team focused on perivascular spaces within the brain.

Because toxins called amyloid plaques (linked to Alzheimer's disease) can build up within these fluid-filled areas, they've long been a target of research in older adults.

Garic and study co-author Mark Shen wondered if they might also play a role in brain health very early in the life span.

As the researchers explained, every six hours cerebrospinal fluid (CSF) pulses through perivascular spaces in the brain, flushing out inflammatory and other waste products that could otherwise hamper brain activity. That waste includes amyloid beta.

This brain-cleansing process is especially active during sleep. And, given that autism and sleep issues often arise together, the UNC team wondered if perivascular spaces might explain why.

From studies in animals and older adults, they already knew that poor sleep can trigger an unhealthy enlargement of perivascular spaces.

Would the same hold true in small kids? To find out, the investigators looked at 870 brain MRIs taken of sleeping children at six, 12 and 24 months of age. These babies were all the younger siblings of kids with autism -- meaning they were already at higher risk of developing the condition.

Their brain MRIs showed a correlation between enlarged perivascular spaces and a later autism diagnosis, the researchers reported.

Kids with enlarged perivascular spaces in their brains before the age of 24 months were 2.2 times more likely to be diagnosed later with autism, compared to kids whose MRIs showed normal-sized perivascular spaces.

Overall, 30% of kids who displayed large perivascular spaces when they were a year old went on to get an autism diagnosis, and nearly half of children later diagnosed with autism displayed enlarged spaces on their MRIs by the age of 2.

Enlarged perivascular spaces in infancy were also strongly linked with sleep disorders seven to 10 years later, the UNC team found.

“These results suggest that perivascular spaces could serve as an early marker for autism,” said Garic, who is also a member of the Carolina Institute for Developmental Disabilities.

“It was really striking to observe such a strong association separated by such a long period of time over childhood," she added. "But it really shows how perivascular spaces not only have an effect early in life, but they can have long term effects, too.”

A "clogging" of cerebrospinal fluid within perivascular spaces early in life could have major consequences on the developing brain, Garic and Shen believe and they plan further research into this issue. They believe it could play a role in other conditions, such as Fragile X syndrome or Down syndrome.

“Collectively our research has shown that CSF abnormalities in the first year of life could have downstream effects on a variety of outcomes, including later autism diagnosis, sleep problems, neuro-inflammation and possibly other developmental disabilities,” said Shen, who is an assistant professor of psychiatry at UNC.

More information

Find out more about autism at Autism Speaks.

SOURCE: University of North Carolina, news release, Jan. 3, 2023