Towards a blood based biomarker for autism?

By Matt Carey

When I attended IMFAR in 2011, the work of Eric Courchesne’s group at UCSD was highlited in the press conference . The main study highlighted was Abnormally Accelerated Development of Higher-Order Long-Distance Cerebral Tracts In ASD Infants and Toddlers, which was a structural (MRI) study of brains in autistic children.

Another study presented by Prof. Courchesne’s group at the conference was Blood-Based Transcriptomic Biomarker Profiles of Autistic Spectrum and Other Developmental Disorders. The results were intriguing: mRNA expression in the blood was different for autistics than either typically developing or developmentally disabled young children. The genes involved were related to mitotic cell cycle regulation as well as cerebral cortex development and other processes which might shed light on etiology. What was particularly intriguiing was the conclusion of the conference abstract:

[peripheral blood mononuclear cells] may serve as a useful tissue for deriving biomarker profiles of ASDs that are highly specific to particular neurodevelopmental disorders. Ongoing longitudinal analyses of these subjects will determine if these blood-based biomarker profiles fluctuate as symptom profiles change over time with intensive behavioral treatment.

In other words: these mRNA expressions might be specific enough to serve as a biomarker.

Blood-based gene expression signatures of infants and toddlers with autism.

OBJECTIVE:
Autism spectrum disorders (ASDs) are highly heritable neurodevelopmental disorders that onset clinically during the first years of life. ASD risk biomarkers expressed early in life could significantly impact diagnosis and treatment, but no transcriptome-wide biomarker classifiers derived from fresh blood samples from children with autism have yet emerged.
METHOD:
Using a community-based, prospective, longitudinal method, we identified 60 infants and toddlers at risk for ASDs (autistic disorder and pervasive developmental disorder), 34 at-risk for language delay, 17 at-risk for global developmental delay, and 68 typically developing comparison children. Diagnoses were confirmed via longitudinal follow-up. Each child’s mRNA expression profile in peripheral blood mononuclear cells was determined by microarray.
RESULTS:
Potential ASD biomarkers were discovered in one-half of the sample and used to build a classifier, with high diagnostic accuracy in the remaining half of the sample.
CONCLUSIONS:
The mRNA expression abnormalities reliably observed in peripheral blood mononuclear cells, which are safely and easily assayed in infants, offer the first potential peripheral blood-based, early biomarker panel of risk for autism in infants and toddlers. Future work should verify these biomarkers and evaluate whether they may also serve as indirect indices of deviant molecular neural mechanisms in autism.

The published study follows the conservative approach of the IMFAR abstract: the title is not focused on the potential for this discovery to be used as a biomarker, but the conclusions point out that this is a possibility. Had I not been watching for published studies such as this from Prof. Courchesne’s group, I might have passed over this abstract after reading the title.

Autism is currently diagnosed based on behaviors. Because of this many autistics are missed. For example, the CDC autism prevalence estimates identify individuals who previously were undiagnosed, and the median age of diagnosis in the recent study from Sweden was 8 years old. A blood based biomarker would be very helpful in helping to provide therapies and supports to autistics from an early age.

Prof Courchesne has worked as a grant reviewer for the Autism Science Foundation.