Brain Chemistry Differs in Autism vs Developmental Delay

Fran Lowry

August 01, 2013

Between the ages of 3 and 10 years, children with autism spectrum disorder (ASD) show brain chemical changes that differ from changes seen in children with developmental delay, new research shows.

Brain scans measuring neurochemical levels in children with ASD and developmental delay showed a "dynamic reversal" of reductions in cerebral gray matter N-acetylaspartate (NAA) in children with ASD.

In contrast, the reductions in gray matter NAA persisted in the children with developmental delay.

The scans also measured neurochemical levels in developmentally normal children and showed that by the time the children with autism had reached the age of 9 or 10, their levels of NAA were similar to those of the normal children.

"The kids with autism had a pattern of normalization of their early brain chemical alterations, so by the time they reached the age of 9 or 10, they had caught up with kids with typical development, whereas the kids with developmental delays showed static alterations during this time frame and didn't catch up with the typically developing kids or the kids with autism," senior author Stephen R. Dager, MD, professor of radiology at the University of Washington, Seattle, told Medscape Medical News.

"There seems to be a dynamic process going on with abnormal brain developmental processes and autism. If our findings hold up, and particularly if we can move this back to even younger ages where we can find a disruption in brain development, we may be able to reduce its impact on downstream effects," he added.

The study was published online July 31 in JAMA Psychiatry.

Kids With Autism Often Catch Up

In the study, led by Neva M. Corrigan, PhD, investigators used magnetic resonance spectroscopic imaging to examine cross-sectional and longitudinal patterns of brain chemical concentrations at 3 different age points, as follows:

  • 3 - 4 years (45 children with ASD, 14 with developmental delay, 14 with typical development)

  • 6 - 7 years (35 children with ASD, 14 with developmental delay, 20 with typical development)

  • 9 - 10 years (29 children with ASD, 15 with developmental delay, and 33 with typical development)

In addition to NAA, the researchers also measured choline, creatine, myo-inositol, and glutamine plus glutamate in cerebral gray matter and white matter.

"N-acetylaspartate is thought to play an important role in regulating synaptic connections and myelination," Dr. Dager said. "Its levels are decreased in people with conditions such as Alzheimer's, traumatic brain injury, or stroke. The other chemicals that we examined, choline, creatine, glutamine and glutamate, and myo-inositol, help characterize brain tissue integrity and bioenergetics status."

Dr. Stephen Dager

A "notable" finding was that NAA concentrations were low in both the ASD and developmentally delayed groups compared with the typical development group in the youngest children in both gray matter (P = .002) and white matter (P < .001).

But by age 9 to 10 years, gray matter NAA levels were lower in the developmentally delayed group compared with the normal group (P = .04). In contrast, in the ASD group, these levels had caught up to the levels in the normal group.

"A substantial number of kids with early, severe autism symptoms make tremendous improvements, and our findings suggest that there is a very different brain developmental process between children with autism and those with developmental delays," said Dr. Dager.

"Our findings support the notion that ASD is different from developmental delay and challenges the notion that the increasing prevalence of autism merely reflects a recategorization of symptoms between autism and intellectual disabilities."

Replication Needed

Commenting on the findings for Medscape Medical News, George M. Anderson, PhD, from Yale University, New Haven, Connecticut, called it "an important contribution to the now more than 20 studies that have used NMR [nuclear magnetic resonance] spectroscopy to measure in vivo levels of neurochemicals in brains of children and adults with autism."

"Making measurements across development is an especially powerful approach, although most of the data were not truly longitudinal in that most children were only scanned at one age," he added.

Dr. George Anderson

Dr. Anderson also said that the conclusions made by the study authors should be viewed as tentative.

"The authors state that the measurements 'differentiated the children with ASD from those with DD [developmental delay],' and that 'age-related alterations [in ASD] between 3 and 10 years of age...were distinct from those found in children with DD.' However, these claims appear overstated if one considers the tremendous overlap seen in the individual data across the groups," Dr. Anderson said.

"Conclusions from this study regarding developmental differences should be tentative, given this overlap," he said.

"It will be important to replicate the observed alterations and to determine whether there is a subgroup of individuals with ASD who display the reported alterations in developmental trajectories," Dr. Anderson said.

The study was supported by the National Institutes of Health. Dr. Dager and Dr. Anderson report no relevant financial relationships.

JAMA Psychiatry. Published online July 31, 2013. Abstract

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