Elevated cerebrospinal fluid levels linked with autism diagnosis, third study confirms

Researchers at the UC Davis MIND Institute and the University of North Carolina have shown for the third time that an increased amount of extra-axial cerebrospinal fluid (CSF) is associated with the diagnosis of autism spectrum disorder in young children. The ability to identify ASD children early could improve both treatment and quality of life. The study was published in the journal The Lancet Psychiatry.

“Our first paper showed that, if you conduct MRIs on children as young as six months who have a high risk for ASD, increased fluid volume predicts a subset of autism,” said David Amaral, professor in the UC Davis Department of Psychiatry and Behavioral Sciences, a MIND Institute researcher and senior author on the paper. “The second study confirmed these results in a larger cohort, and now we have validated them a third time in older children with varying degrees of risk.”

The kids in these studies were recruited through the Autism Phenome Project at the MIND Institute, which tracks children from initial diagnosis to identify biological subtypes of ASD.

CSF was once thought to be relatively benign, providing shock absorption to protect the brain.However, newer findings have shown that CSF acts as a cleaning agent, removing potentially harmful molecules, particularly during sleep.

While the first two studies looked at kids who had an older sibling with ASD, and were therefore at higher familial risk, the current paper studied both high-risk and low-risk children. In addition, the investigators extended the monitoring period to determine if the increased CSF was present at an older age.

There were 236 children, with an average age of 3 years, in the study – 159 with ASD and 77 with typical development. Researchers conducted brain MRIs to measure CSF, and sophisticated algorithms assessed the results to develop predictive biomarkers.

The study found that increased CSF levels were still present in 3-year-old kids. Moreover, children with ASD had elevated CSF, regardless of familial risk background, compared to typically developing children. These brain measures distinguished kids with autism from those with typical development with 83 percent accuracy.

“We knew from our previous studies that it was present at six months, and this study in a different group of children showed CSF was abnormally increased at age three,” said Mark Shen, assistant professor in the UNC Department of Psychiatry and first author on the paper. “It appears to be present in high-risk kids with autism, as well as kids with autism from the general community.”

The study also showed that children with more CSF had greater sleep problems. This is important because proper CSF circulation, particularly during sleep, is essential to brain health.

“Sleep is when this brain fluid is supposed to be circulating around the brain and cleaning it,” said Shen. “When someone doesn’t get enough sleep, there is a possibility for buildup of proteins that can affect learning, memory and general brain function.”

It’s unclear whether increased fluid may contribute to one of the causes of autism or is simply a side effect of the underlying biology. However, with further research, CSF could eventually become a therapeutic target.

These findings provide a replicated indication that the signs of autism begin very early in life and could contribute to early detection of risk for autism. Early detection could increase the therapeutic window, giving kids earlier access to therapy.

“Getting younger children into intensive behavioral therapy would be very helpful,” said Amaral. “And, if there is a biological treatment, it would be great to get them on it at six months, rather than three or four years when kids are often diagnosed.”

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