Children with enlarged brains are at a higher risk of autism, study suggests

For the first time, scientists have discovered a link between a child’s brain size and makeup to a future autism diagnosis. 

Researchers from the University of North Carolina‘s school of medicine found infants with a family history of autism and an abnormally large part of their brain had a 2.2 times greater chance of developing autism compared to infants with the same genetic predisposition but who had normal sized brains. 

Throughout the brain, cerebrospinal fluid (CSF) travels through small fluid-filled channels called perivascular spaces (PVS). 

Perivascular spaces regulate fluid movement in the central nervous and its drainage.  

CSF is a body fluid in the tissue surrounding the brain and spinal cord. The colorless fluid assists the brain by providing protection, nourishment and waste removal, flushing out neuroinflammation and other neurological waste. 

A disruption to this key process can lead to neurological dysfunction, cognitive decline or developmental delays.

The study, published in JAMA Network Open found kids with enlarged perivascular spaces had a higher risk of being diagnosed with autism by two years old. 

Dr Dea Garic, co-author of the study and professor of psychiatry, said: ‘These results suggest that perivascular spaces could serve as an early marker for autism.’ 

The above graph shows the association between enlarged perivascular spaces and a future diagnosis of autism. High likelihood of autism is defined as having a family history of the disorder and low likelihood is defined as having no predisposition for autism

The above shows a scan of a 24-month-old study subject’s brain with cerebrospinal fluid (blue) and perivascular space (green) labeled

The research also showed enlarged spaces in infancy was associated with sleep problems seven to 10 years after diagnosis. 

For the study, researchers analyzed and scanned the brains of 311 infants, which included kids who had an increased risk of autism because of an older sibling with the disorder and those who did not have a familial risk. 

They followed participants from six to 24 months of age, before any had received an autism diagnosis. Brain images were taken at six months, 12 months and 24 months of age to observe changes over time. 

Over the course of the study, 30 percent of infants who later developed autism had enlarged perivascular spaces by 12 months of age. 

At 24 months, nearly half of infants diagnosed with the disorder had the enlarged spaces. 

It was also discovered that excessive CSF volume in children six months old was linked to enlarged PVS at two years old. 

The scientists also examined whether PVS and CSF volume had an effect on sleep issues later in childhood. 

Every six hours, the brain sends out CSF to the PVS to remove harmful proteins – which can include the amyloid proteins linked to Alzheimer’s disease. 

The CSF cleanup process is extra efficient during sleep, with a majority of circulation and clearance occurring during shut eye. Disrupted sleep, however, reduces CSF clearance from PVS, which enlarges or distorts the spaces. 

The sleep analysis revealed children who had enlarged PVS at two years of age had higher rates of sleep disturbances between seven and 12 years old. 

While this has been previously studied in animals, this study is the first to examine the relationship in children. 

Dr Garic added: ‘Since autism is so highly linked with sleep problems, we were in this unique position to examine CSF dynamics and sleep. 

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

Autism is notoriously hard to spot, with the average age of diagnosis around five years old in the US. The process usually involves dozens of trips to multiple doctors and a battery of tests, which can be stressful for children and families. 

The disorder affects one in 36 children, meaning  more than 90,000 children are born annually with the developmental disorder in the US.

Autism is characterized by problems with social communication and interaction, difficulty expressing oneself and repetitive behaviors and interests.

Senior author of the study Dr Mark Shen said: ‘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, neuroinflammation, and possibly, other developmental disabilities.’

And Dr Garic added: ‘Our findings were striking, given that neuroradiologists typically view enlarged perivascular spaces as a sign of neurodegeneration in adults, but this study reported it in toddlers.

‘This is an important aspect of brain development in the first years of life that should be monitored.’