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Regulation of Cerebral Cortical Size and Neuron Number by Fibroblast Growth Factors: Implications for Autism

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Abstract

Increased brain size is common in children with autism spectrum disorders. Here we propose that an increased number of cortical excitatory neurons may underlie the increased brain volume, minicolumn pathology and excessive network excitability, leading to sensory hyper-reactivity and seizures, which are often found in autism. We suggest that Fibroblast Growth Factors (FGF), a family of genes that regulate cortical size and connectivity, may be responsible for these developmental alterations. Studies in animal models suggest that mutations in FGF genes lead to altered cortical volume, excitatory cortical neuron number, minicolum pathology, hyperactivity and social deficits. Thus, many risk factors may converge upon FGF-regulated pathogenetic pathways, which alter excitatory/inhibitory balance and cortical modular architecture, and predispose to autism spectrum disorders.

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Acknowledgments

This work was supported by NIH grants MH067715, Autism Speaks and the NARSAD Foundation. We thank Shawna Ellis for technical assistance and all members of the Vaccarino lab for helpful discussions.

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Authors and Affiliations

  1. Child Study Center, Yale University School of Medicine, 230 South Frontage Rd, New Haven, CT, 06520, USA

    Flora M. Vaccarino, Elena L. Grigorenko, Karen Müller Smith & Hanna E. Stevens

  2. Department of Neurobiology, Yale University School of Medicine, 230 South Frontage Rd, New Haven, CT, 06520, USA

    Flora M. Vaccarino

  3. Department of Psychology and Department of Epidemiology and Public Health, Yale University, 230 South Frontage Rd, New Haven, CT, 06520, USA

    Elena L. Grigorenko

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  1. Flora M. Vaccarino
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  2. Elena L. Grigorenko
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  3. Karen Müller Smith
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  4. Hanna E. Stevens
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Correspondence to Flora M. Vaccarino.

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Vaccarino, F.M., Grigorenko, E.L., Smith, K.M. et al. Regulation of Cerebral Cortical Size and Neuron Number by Fibroblast Growth Factors: Implications for Autism. J Autism Dev Disord 39, 511–520 (2009). https://doi.org/10.1007/s10803-008-0653-8

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  • DOI: https://doi.org/10.1007/s10803-008-0653-8

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