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

J Am Acad Child Adolesc Psychiatry. 2012 Sep;51(9):934-44.e2. doi: 10.1016/j.jaac.2012.07.007. Epub 2012 Aug 2.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child Development Disorders, Pervasive / blood
  • Child Development Disorders, Pervasive / diagnosis
  • Child Development Disorders, Pervasive / genetics*
  • Child, Preschool
  • Cross-Sectional Studies
  • DNA Probes / genetics
  • Female
  • Gene Expression Profiling
  • Genetic Markers / genetics
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Infant
  • Language Development Disorders / blood
  • Language Development Disorders / diagnosis
  • Language Development Disorders / genetics
  • Leukocytes, Mononuclear / metabolism*
  • Longitudinal Studies
  • Male
  • Oligonucleotide Array Sequence Analysis
  • Prospective Studies
  • RNA, Messenger / genetics
  • Reference Values
  • Transcriptome / genetics*

Substances

  • DNA Probes
  • Genetic Markers
  • RNA, Messenger