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Autism spectrum disorders: multiple routes to, and multiple consequences of, abnormal synaptic function and connectivity

Autism spectrum disorders: multiple routes to, and multiple consequences of, abnormal synaptic function and connectivity
Autism spectrum disorders: multiple routes to, and multiple consequences of, abnormal synaptic function and connectivity
Autism spectrum disorders (ASDs) are a heterogeneous group of neurodevelopmental disorders of genetic and environmental etiologies. Some ASD cases are syndromic: associated with clinically defined patterns of somatic abnormalities and a neurobehavioral phenotype (e.g., Fragile X syndrome). Many cases, however, are idiopathic or non-syndromic. Such disorders present themselves during the early postnatal period when language, speech, and personality start to develop. ASDs manifest by deficits in social communication and interaction, restricted and repetitive patterns of behavior across multiple contexts, sensory abnormalities across multiple modalities and comorbidities, such as epilepsy among many others. ASDs are disorders of connectivity, as synaptic dysfunction is common to both syndromic and idiopathic forms. While multiple theories have been proposed, particularly in idiopathic ASDs, none address why certain brain areas (e.g., frontotemporal) appear more vulnerable than others or identify factors that may affect phenotypic specificity. In this hypothesis article, we identify possible routes leading to, and the consequences of, altered connectivity and review the evidence of central and peripheral synaptic dysfunction in ASDs. We postulate that phenotypic specificity could arise from aberrant experience-dependent plasticity mechanisms in frontal brain areas and peripheral sensory networks and propose why the vulnerability of these areas could be part of a model to unify preexisting pathophysiological theories.
autism spectrum disorders, connectivity, maternal immune activation, neurodevelopment, pain sensitivity, phenotypic specificity, synaptic dysfunction, synaptic plasticity
1073-8584
Carroll, Liam
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Braeutigam, Sven
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Dawes, John M.
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Krsnik, Zeljka
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Kostovic, Ivica
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Coutinho, Ester
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Dewing, Jennifer
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Horton, Christopher
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Gomez-Nicola, Diego
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Menassa, David
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Carroll, Liam
0b20d32e-6712-4b8b-ac98-8174ef628a7c
Braeutigam, Sven
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Dawes, John M.
602cbc93-bce5-4e0e-924b-7cad5f9571ce
Krsnik, Zeljka
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Kostovic, Ivica
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Coutinho, Ester
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Dewing, Jennifer
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Horton, Christopher
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Gomez-Nicola, Diego
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Menassa, David
eeb394a6-c72b-49d7-a820-95b0256c22d5

Carroll, Liam, Braeutigam, Sven, Dawes, John M., Krsnik, Zeljka, Kostovic, Ivica, Coutinho, Ester, Dewing, Jennifer, Horton, Christopher, Gomez-Nicola, Diego and Menassa, David (2020) Autism spectrum disorders: multiple routes to, and multiple consequences of, abnormal synaptic function and connectivity. The Neuroscientist. (doi:10.1177/1073858420921378).

Record type: Review

Abstract

Autism spectrum disorders (ASDs) are a heterogeneous group of neurodevelopmental disorders of genetic and environmental etiologies. Some ASD cases are syndromic: associated with clinically defined patterns of somatic abnormalities and a neurobehavioral phenotype (e.g., Fragile X syndrome). Many cases, however, are idiopathic or non-syndromic. Such disorders present themselves during the early postnatal period when language, speech, and personality start to develop. ASDs manifest by deficits in social communication and interaction, restricted and repetitive patterns of behavior across multiple contexts, sensory abnormalities across multiple modalities and comorbidities, such as epilepsy among many others. ASDs are disorders of connectivity, as synaptic dysfunction is common to both syndromic and idiopathic forms. While multiple theories have been proposed, particularly in idiopathic ASDs, none address why certain brain areas (e.g., frontotemporal) appear more vulnerable than others or identify factors that may affect phenotypic specificity. In this hypothesis article, we identify possible routes leading to, and the consequences of, altered connectivity and review the evidence of central and peripheral synaptic dysfunction in ASDs. We postulate that phenotypic specificity could arise from aberrant experience-dependent plasticity mechanisms in frontal brain areas and peripheral sensory networks and propose why the vulnerability of these areas could be part of a model to unify preexisting pathophysiological theories.

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e-pub ahead of print date: 22 May 2020
Keywords: autism spectrum disorders, connectivity, maternal immune activation, neurodevelopment, pain sensitivity, phenotypic specificity, synaptic dysfunction, synaptic plasticity

Identifiers

Local EPrints ID: 441099
URI: http://eprints.soton.ac.uk/id/eprint/441099
ISSN: 1073-8584
PURE UUID: 8e3c56e4-896c-41e2-90a7-ddca0ea7aa30
ORCID for Diego Gomez-Nicola: ORCID iD orcid.org/0000-0002-5316-2682

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Date deposited: 01 Jun 2020 16:31
Last modified: 28 Apr 2022 02:03

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Contributors

Author: Liam Carroll
Author: Sven Braeutigam
Author: John M. Dawes
Author: Zeljka Krsnik
Author: Ivica Kostovic
Author: Ester Coutinho
Author: Jennifer Dewing
Author: Christopher Horton
Author: David Menassa

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