title: Age-related decreased inhibitory vs. excitatory gene expression in the adult autistic brain.
abstract: Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by impaired social interaction and communication, and restricted behavior and interests. A disruption in the balance of excitatory and inhibitory neurotransmission has been hypothesized to underlie these disorders. Here we demonstrate that genes of both pathways are affected by ASD, and that gene expression of inhibitory and excitatory genes is altered in the cerebral cortex of adult but not younger autistic individuals. We have developed a measure for the difference in the level of excitation and inhibition based on gene expression and observe that in this measure inhibition is decreased relative to excitation in adult ASD compared to control. This difference was undetectable in young autistic brains. Given that many psychiatric features of autism are already present at an early age, this suggests that the observed imbalance in gene expression is an aging phenomenon in ASD rather than its underlying cause.
authors.affiliation: Centre for Neuroregeneration and Centre for Clinical Brain Sciences, University of Edinburgh Edinburgh, UK.
authors.forename: Louie N
authors.initials: LN
authors.lastname: van de Lagemaat
authors.affiliation: Department of Human Genetics, Radboud University Medical Center Nijmegen, Netherlands.
authors.forename: Bonnie
authors.initials: B
authors.lastname: Nijhof
authors.affiliation: Department of Human Genetics, Radboud University Medical Center Nijmegen, Netherlands ; Bartiméus, Institute for the Visually Impaired Zeist, Netherlands ; Radboud Institute for Molecular Life Science, Radboud University Medical Center Nijmegen, Netherlands ; Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center Nijmegen, Netherlands.
authors.forename: Daniëlle G M
authors.initials: DG
authors.lastname: Bosch
authors.affiliation: Department of Neurobiology, Max Planck Institute for Biophysical Chemistry Göttingen, Germany.
authors.forename: Mahdokht
authors.initials: M
authors.lastname: Kohansal-Nodehi
authors.affiliation: Department of Biochemistry, La Trobe Institute for Molecular Science 1, La Trobe University Melbourne, VIC, Australia.
authors.forename: Shivakumar
authors.initials: S
authors.lastname: Keerthikumar
authors.affiliation: Cortical Structure and Function Group, Netherlands Institute for Neuroscience Amsterdam, Netherlands.
authors.forename: J Alexander
authors.initials: JA
authors.lastname: Heimel
keywords: age effect; autism; balance; excitation; gene expression; inhibition