UC DAVIS (US) — Preschool boys with regressive autism—but not those with early onset autism—have larger brains than healthy boys their age, a new study shows.
There is no evidence of similar findings for girls with any form of autism.
Brain enlargement has been observed in previous studies of autism, but prior to the new research reported online in Proceedings of the National Academy of Sciences, little was known about how many and which children with autism have abnormally large brains.
“The finding that boys with regressive autism show a different form of neuropathology than boys with early onset autism is novel,” says Christine Wu Nordal, assistant professor of psychiatry at the University of California, Davis and a researcher at the MIND Institute.
“Moreover, when we evaluated girls with autism separately from boys, we found that no girls—regardless of whether they had early onset or regressive autism—had abnormal brain growth,” says Nordal.
“This adds to the growing evidence that there are multiple biological subtypes of autism, with different neurobiological underpinnings,” says co-author David Amaral, professor of psychiatry and behavioral sciences and research director at the MIND Institute.
Autism is a neurodevelopmental disorder whose symptoms include deficits in language and social interaction and communication. The condition affects 1 in 110 children born today, according to the U.S. Centers for Disease Control and Prevention. It is diagnosed more frequently in male children than female children—at a ratio of 4 to 1.
For the study, the authors enrolled a total of 180 children between age 2 and 4. Of the total, 114 participants had autism spectrum disorder; the remaining participants were 66 age-matched typically developing controls. Of the children with autism, 54 percent were diagnosed with the regressive form and 46 with the non-regressive type.
Magnetic resonance imaging (MRI) scans were collected from the participants at age 3. To evaluate the rate of brain growth prior to age 3, they analyzed head circumference measurements taken from pediatric well-baby visits from birth through 18 months. Roughly half of the children with autism were reported by their parents as having experienced a regression, characterized by the loss of previously acquired language and social skills.
The MRIs were carried out on study participants during natural, nighttime sleep using protocols developed specifically for the Autism Phenome Project by Nordahl.
“Obtaining MRI scans in 3-year-old children without the use of sedation may seem quite challenging. But, by working closely with the parents, we actually were successful more than 85 percent of the time. Patience on the part of everyone and the dedication of the families was critical for our success,” Nordahl says.
The study found that accelerated head growth and brain enlargement was consistently observed only in the subset of children diagnosed with regressive autism. Specifically, total brain volume in 3-year-old males with regressive autism was more than 6 percent larger than that of age-matched typically developing peers. Twenty-two percent of boys with regressive autism, as opposed to 5 percent of boys without regressive autism, had enlarged brains.
Changes in brain size were not apparent in boys who did not experience a regression. Girls with autism, regardless of autism onset status, also did not show abnormal brain growth. The study findings suggest that abnormalities in overall brain growth are specific to male children with the regressive type of autism, and that rapid brain growth may be a risk factor for regression, the researchers said.
While brain size was clearly larger at age 3, the study also determined when the precocious growth began, by examining records of head circumference that provides a reasonable estimate of brain size in young children.
These analyses clearly indicated that brain growth diverged from normal at around 4 to 6 months of age. This is of particular interest, because many families believe that the trigger that led to their child’s regression took place close to the time that the regression happened. But the data indicates that the process leading to the enlarged brain, which presumably also is associated with the onset of autism, started when the child was a newborn.
Much remains to be determined regarding brain changes associated with autism, the authors say. In the current study, not all boys with regression demonstrate the precocious brain growth. The researchers plan to continue efforts to define the underlying brain pathology in children with early onset autism and in girls with autism.
“It is not clear how many different types of autism will be identified,” Amaral says. “The purpose of defining different types of autism is to more effectively study the cause of each type and eventually determine effective preventative measures and better, individualized treatments.
“This is a first step in defining autism subtypes based on the data from the Autism Phenome Project, but it certainly will not be the last. There are already indications that other subtypes of autism will be more closely associated with immunological differences or genetic alterations.”
Researchers from Harvard University contributed to the study that was funded by by grants from the National Institute of Mental Health and the University of California, Davis Medical Investigation of Neurodevelopmental Disorders (MIND) Institute.
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