Brain Enlargement Tied to Regressive Autism, but Only in Boys

Megan Brooks

December 01, 2011

December 1, 2011 — Preschool-age boys with regressive autism, but not those with early-onset autism, have larger brains than typically developing boys of the same age, new research suggests.

However, the investigators found no evidence of brain enlargement in preschool-age girls with any form of autism.

"This study highlights the complexity and heterogeneity of autism," the investigators, David G. Amaral, PhD, and Christine Wu Nordahl, PhD, from the University of California, Davis, Medical Investigation of Neurodevelopmental Disorders Institute in Sacramento, write. "These results suggest that there may distinct neural phenotypes associated with different onsets of autism."

The study was published online November 28 in Proceedings of the National Academy of Sciences.

Consistent With Regressive Autism

Autism typically presents in the first 3 years of life, but in cases of regressive autism, a child appears to be developing normally and then suddenly starts to regress; they lose language and social skills, typically between the ages of 15 and 30 months, and are subsequently diagnosed with the disorder.

The study involved 180 boys and girls between 2 and 4 years old, 114 of whom had autism-spectrum disorder (ASD). Of these, 61 patients had regressive autism (54%), and 53 (46%) did not. The rate of regressive autism in the sample mirrors that of recent population-based studies. The remaining 66 children in the study had no signs of autism and served as typically developing controls.

At age 3 years, all of the children underwent magnetic resonance imaging (MRI) during natural, nighttime sleep protocols that the study team developed.

"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% of the time," Dr. Nordahl said in a statement.

According to the researchers, abnormal brain enlargement was most consistently observed in the boys with regressive autism.

"Brain size in boys without regression did not differ from controls," they report.

Total brain volume in boys with regressive autism was 6.2% larger than that of their typically developing peers; 22% of boys with regressive autism had megalencephaly compared with 5% of boys without regressive autism. Boys with early-onset autism had total cerebral volume similar to that of the control patients.

Point of Divergence

A medical chart review of serial head circumference measurements obtained at well-child visits from birth to 18 months of age found that head circumference in boys with regressive autism is normal at birth but diverges from the other groups around 4 to 6 months of age.

"For boys with regressive autism, divergence in brain size occurs well before loss of skills is commonly reported," the authors note. "Thus, rapid head growth may be a risk factor for regressive autism."

"Acceleration of head growth around 4 to 6 months of age may suggest that the infant should be monitored more closely for any loss of skills, and earlier behavioral intervention could be initiated," Dr. Nordahl told Medscape Medical News.

Brain enlargement was not evident in girls with ASD, regardless of whether they had the early-onset or regressive form of the disorder. These findings, say the researchers, provide suggestive evidence that the biological underpinnings of early-onset and regressive forms of autism are different.

The researchers emphasize that much remains to be elucidated regarding abnormal brain growth in autism.

"We will spend increasing amounts of time trying to relate these data across disciplines. For example: Is there a particular genetic fingerprint that is associated with the big brains?" Dr. Amaral told Medscape Medical News.

"We would also like to increase the cohort of children by at least 250. This would allow us to have sufficient statistical power to examine biological differences in girls with autism," he added.

Dr. Nordahl said the fact that autism occurs at a 4-to-1 ratio of boys to girls poses a research challenge.

"It is difficult to recruit large enough sample sizes of females with autism to evaluate their neural differences independently from boys with autism. We hope to continue to study the neuropathology of girls with autism," she said.

Interpret Cautiously

Commenting on the study for Medscape Medical News, Eric Courchesne, PhD, from the Autism Center of Excellence, University of California, San Diego, School of Medicine in La Jolla, said it should be noted that other studies have found abnormal brain enlargement in girls with autism and that the largest brain size on record for autism is a girl with autism.

He also noted that other large studies have found enlargement in a substantial percentage of boys who did not display regression, as well as those who did.

"The differences between studies," he said, "may reflect that some studies recruited from a selected subset of the population of individuals with autism, while others recruit and report on autism as it occurs in the general pediatric population."

The study was supported by grants from the National Institute of Mental Health and the University of California, Davis, Medical Investigation of Neurodevelopmental Disorders Institute. The study investigators and Dr. Courchesne have disclosed no relevant financial relationships.

Proc Natl Acad Sci. Published online November 28, 2011. Full text


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: