Atypical architecture of prefrontal cortex in young children with autism

  • Awarded: 2010
  • Award Type: Research
  • Award #: 176540

Autism impairs the development of social behavior, emotions and communication. The prefrontal cortex plays an important role in the early development of these skills and displays abnormal growth and function in children with autism. Few studies have looked for autism-associated neural defects in this region in young children.

Eric Courchesne and his colleagues at the University of California, San Diego, are using postmortem tissue from young children with autism (aged 2 to 14 years) to identify abnormalities in prefrontal cortex structure and gene expression starting when the symptoms of autism become apparent, through preadolescence. Because development is a continuous process, later growth can mask early events, and analysis of young tissue is essential for understanding the dynamics of early development.

Courchesne has found that toddlers and young children with autism consistently have an atypical architecture of neurons in the prefrontal cortex. This architecture may be a common neural defect that predisposes a child to developing autism. In a parallel experiment using postmortem tissue from people with autism, the researchers performed whole-genome analyses of gene expression in the same regions of the prefrontal cortex. They uncovered evidence of disruption in early developmental processes that regulate neuron numbers, DNA integrity, neuron migration and neural patterning. In another experiment, the researchers found 67 percent more neurons in the prefrontal cortex of young boys (aged 2 to 16 years) with autism than in age-matched controls.

Courchesne and his colleagues propose to investigate how common these cortical defects are across age, gender and level of functioning in autism. They also plan to analyze the structural and genetic properties of cells that make up the atypical architecture. This work may lead to new methods for determining early risk and prognosis, and possibly to new therapies for autism.

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