Age-related decreased inhibitory vs. excitatory gene expression in the adult autistic brain.

Louie N. van de Lagemaat; Bonnie Nijhof; Daniëlle G. M. Bosch; Madokht Kohansal-Nodehi; Shivakumar Keerthikumar; J. Alexander Heimel

doi:10.3389/fnins.2014.00394

Age-related decreased inhibitory vs. excitatory gene expression in the adult autistic brain.

Louie N. van de Lagemaat^* (Corresponding Author)
, Bonnie Nijhof
, Daniëlle G. M. Bosch
, Madokht Kohansal-Nodehi
, Shivakumar Keerthikumar
, J. Alexander Heimel

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

14 Citations (Scopus)

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.

Original language	English
Article number	394
Number of pages	9
Journal	Frontiers in Neuroscience
Volume	8
DOIs	https://doi.org/10.3389/fnins.2014.00394
Publication status	Published - 8 Dec 2014
Externally published	Yes

Bibliographical note

Acknowledgments
We thank sister Scholastica, the Abtei Frauenwörth, the INCF and the Centre of Integrative and Translational Genomics for providing a stimulating environment that led to this fruitful collaboration, and Richard Nowakowski for commenting on an early version of the manuscript. Thanks to Alberto Capurro and Ruth Luthi-Carter for help to understand the PSEA method. We are also greatly indebted to the patients and their families who have contributed tissue to the original data analyses, and acknowledge Drs. Geschwind and Courchesne and public databases for enabling data mining collaborations such as this one.

Keywords

autism
excitation
inhibition
balance
gene expression
age effect

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10.3389/fnins.2014.00394Licence: CC BY

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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.",

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AU - Kohansal-Nodehi, Madokht

AU - Keerthikumar, Shivakumar

AU - Heimel, J. Alexander

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N2 - 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.

AB - 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.

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JO - Frontiers in Neuroscience

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Age-related decreased inhibitory vs. excitatory gene expression in the adult autistic brain.

Abstract

Bibliographical note

Keywords

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