Cerebrospinal fluid shows promise as autism biomarker

March 6, 2017, UC Davis
David Amaral, PhD, is Beneto Foundation Chair and Director of Research, MIND Institute; University of California Distinguished Professor, Department of Psychiatry and Behavioral Sciences and Center for Neuroscience, School of Medicine; Core Investigator, California National Primate Research Center. Credit: UC Regents

Researchers from the UC Davis MIND Institute, University of North Carolina (UNC) and other institutions have found that altered distribution of cerebrospinal fluid (CSF) in high-risk infants can predict whether they will develop autism spectrum disorder (ASD). The study appears March 6 in the journal Biological Psychiatry.

"Normally, is diagnosed when the child is two or three years old and beginning to show behavioral symptoms; there are currently no early biological markers" said David Amaral, director of research at the MIND Institute and a co-senior author on the paper. "That there's an alteration in the distribution of cerebrospinal fluid that we can see on MRIs as early as six months, is a major finding."

Produced by the brain, CSF was once cast as a neural shock absorber, keeping the brain from bumping up against the skull. More recent findings have shown that CSF can influence neuronal migration and other mechanisms associated with brain development, as well as removing dangerous molecules.

"CSF is like the filtration system in the brain," said Mark Shen, a former graduate student in the Amaral lab and now a postdoctoral fellow in Joseph Piven's lab at UNC. Piven is co-senior author on the paper, and Shen is first author. "As CSF circulates through the brain, it washes away waste particles that would otherwise build up. We believe that extra-axial CSF is an early sign that CSF is not filtering and draining when it should. The result is that there could be a buildup of neuro-inflammation that isn't being washed way."

This study confirms earlier research carried out at the MIND Institute that showed infants with increased CSF in the subarachnoid space (near the brain's perimeter) have increased risk of developing autism. The current study sought to validate the previous results in a larger sample of infants in the Infant Brain Imaging Study (IBIS), a national research network of institutions led by Piven at UNC, Washington University, Children's Hospital of Philadelphia and University of Washington.

To test whether CSF might indicate increased risk of developing ASD, the researchers examined MRIs from 343 infants at six, 12 and 24 months. In this group, 221 babies had older siblings with ASD and were therefore at higher risk for autism. The other 122 subjects had no family history.

Infants who later developed ASD had significantly more subarachnoid CSF at six months than those who did not develop the condition. Among high-risk infants, those who were ultimately diagnosed with ASD had 18 percent more. These measurements predicted ASD in the high-risk group with roughly 70 percent accuracy.

"The more extra-axial CSF present at six months, the more severe the autism symptoms when the kids were diagnosed at 24 months of age," noted Shen.

Finding biomarkers for autism, or any disorder, can be tricky. Quite often, early successes are never replicated. That this larger, more robust, follow-up study confirms the earlier finding is a significant step forward, the researchers said.

Still, this is early work and there are many unanswered questions. The researchers do not know whether the CSF accumulation contributes to autism or is simply an effect from another, more subtle, cause.

In addition, the biomarker is not sensitive enough to say with certainty that a child will develop ASD. However, the apparent link between increased CSF and autism could have significant clinical impact.

"Prior to our 2013 study, radiologists would often call this 'benign extra-axial fluid,' meaning it had no clinical significance," Amaral said. "This finding may alert radiologists and neurologists to the possible negative consequences of increased subarachnoid CSF."

Ultimately, with more study, CSF could help gauge a child's risk of developing ASD and possibly other neurological disorders.

"Neuroimaging CSF could be another tool to help pediatricians diagnose autism as early as possible," said Shen. "It could help signal risk using regular MRIs that you find in any hospital because it is easily seen with the naked eye on a standard MRI."

Explore further: Excessive cerebral spinal fluid, enlarged brain size in infancy are potential biomarkers for autism

Related Stories

Excessive cerebral spinal fluid, enlarged brain size in infancy are potential biomarkers for autism

July 9, 2013
Children who were later diagnosed with autism spectrum disorder had excessive cerebral spinal fluid and enlarged brains in infancy, a study by a multidisciplinary team of researchers with the UC Davis MIND Institute has found, ...

Brain network connections may underlie social behavior linked to autism

February 10, 2017
Evaluating the strength of connections in the brain is one avenue researchers have been exploring to help identify children at risk for autism spectrum disorder earlier in life.

Atypical brain circuits may cause slower gaze shifting in infants who later develop autism

March 20, 2013
Infants at 7 months of age who go on to develop autism are slower to reorient their gaze and attention from one object to another when compared to 7-month-olds who do not develop autism, and this behavioral pattern is in ...

Researchers find autism biomarkers in infancy

February 15, 2017
By using magnetic resonance imaging (MRI) to study the brains of infants who have older siblings with autism, scientists were able to correctly identify 80 percent of the babies who would be subsequently diagnosed with autism ...

Brain-imaging differences evident at 6 months in infants who develop autism

February 17, 2012
A new study led by the University of North Carolina at Chapel Hill found significant differences in brain development starting at age 6 months in high-risk infants who later develop autism, compared to high-risk infants who ...

Brain scans detect early signs of autism

June 27, 2012
A new study shows significant differences in brain development in high-risk infants who develop autism starting as early as age 6 months. The findings published in the American Journal of Psychiatry reveal that this abnormal ...

Recommended for you

Genes contribute to biological motion perception and its covariation with autistic traits

January 22, 2018
Humans can readily perceive and recognize the movements of a living creature, based solely on a few point-lights tracking the motion of the major joints. Such exquisite sensitivity to biological motion (BM) signals is essential ...

Nearly imperceptible fluctuations in movement correspond to autism diagnoses

January 17, 2018
A new study led by researchers at Indiana University and Rutgers University provides the strongest evidence yet that nearly imperceptible changes in how people move can be used to diagnose neurodevelopmental disorders, including ...

Epigenetics study helps focus search for autism risk factors

January 16, 2018
Scientists have long tried to pin down the causes of autism spectrum disorder. Recent studies have expanded the search for genetic links from identifying genes toward epigenetics, the study of factors that control gene expression ...

Being bilingual may help autistic children

January 16, 2018
Children with Autism Spectrum Disorders (ASD) often have a hard time switching gears from one task to another. But being bilingual may actually make it a bit easier for them to do so, according to a new study which was recently ...

No rise in autism in US in past three years: study

January 2, 2018
After more than a decade of steady increases in the rate of children diagnosed with autism in the United States, the rate has plateaued in the past three years, researchers said Tuesday.

Autism therapy: Brain stimulation restores social behavior in mice

December 13, 2017
Scientists are examining the feasibility of treating autistic children with neuromodulation after a new study showed social impairments can be corrected by brain stimulation.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.