Neural excitation/inhibition imbalance and neurodevelopmental pathology in human copy number variant syndromes: a systematic review

Abstract Cumulative evidence suggests neurodevelopmental disorders are closely related. The risk of these disorders is increased by a series of copy number variant syndromes – phenotypically heterogeneous genetic disorders, present in a minority of the population. Recent models suggest that a disrup...

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Main Authors: Amy L. Sylvester, Eva Hensenne, Dimo Ivanov, Benedikt A. Poser, David E. J. Linden, Thérèse van Amelsvoort, Claudia Vingerhoets
Format: Article
Language:English
Published: BMC 2025-06-01
Series:Journal of Neurodevelopmental Disorders
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Online Access:https://doi.org/10.1186/s11689-025-09614-8
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author Amy L. Sylvester
Eva Hensenne
Dimo Ivanov
Benedikt A. Poser
David E. J. Linden
Thérèse van Amelsvoort
Claudia Vingerhoets
author_facet Amy L. Sylvester
Eva Hensenne
Dimo Ivanov
Benedikt A. Poser
David E. J. Linden
Thérèse van Amelsvoort
Claudia Vingerhoets
author_sort Amy L. Sylvester
collection DOAJ
description Abstract Cumulative evidence suggests neurodevelopmental disorders are closely related. The risk of these disorders is increased by a series of copy number variant syndromes – phenotypically heterogeneous genetic disorders, present in a minority of the population. Recent models suggest that a disruption in the balance between excitatory and inhibitory neural activity may contribute to the aetiology of neurodevelopmental disorders, and may be additionally disturbed in copy number variant syndromes. In this systematic review, the databases PubMed, Embase, and Scopus were searched for studies of excitation/inhibition imbalance in relation to neurodevelopmental disorders in human copy number variant samples. A total of 53 studies were included, representing a variety of copy number variants and research methodologies. The resulting data suggests excitation/inhibition balance is indeed disrupted in different copy number variant populations, providing insight into a putative mechanism of both idiopathic and genetic neurodevelopmental disorders. However, the high level of heterogeneity in the data set, alongside emerging techniques for excitation/inhibition assessment, prompts further investigation of this field.
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publishDate 2025-06-01
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spelling doaj-art-6b8aae5d4a314458bb8ae1e19e0cde002025-08-20T03:20:59ZengBMCJournal of Neurodevelopmental Disorders1866-19552025-06-0117113010.1186/s11689-025-09614-8Neural excitation/inhibition imbalance and neurodevelopmental pathology in human copy number variant syndromes: a systematic reviewAmy L. Sylvester0Eva Hensenne1Dimo Ivanov2Benedikt A. Poser3David E. J. Linden4Thérèse van Amelsvoort5Claudia Vingerhoets6Department of Psychiatry and Neuropsychology, Mental Health and Neuroscience Research Institute, Maastricht UniversityDepartment of Psychiatry and Neuropsychology, Mental Health and Neuroscience Research Institute, Maastricht UniversityDepartment of Cognitive Neuroscience, Faculty of Psychology and Neuroscience, Maastricht UniversityDepartment of Cognitive Neuroscience, Faculty of Psychology and Neuroscience, Maastricht UniversityDepartment of Psychiatry and Neuropsychology, Mental Health and Neuroscience Research Institute, Maastricht UniversityDepartment of Psychiatry and Neuropsychology, Mental Health and Neuroscience Research Institute, Maastricht UniversityDepartment of Psychiatry and Neuropsychology, Mental Health and Neuroscience Research Institute, Maastricht UniversityAbstract Cumulative evidence suggests neurodevelopmental disorders are closely related. The risk of these disorders is increased by a series of copy number variant syndromes – phenotypically heterogeneous genetic disorders, present in a minority of the population. Recent models suggest that a disruption in the balance between excitatory and inhibitory neural activity may contribute to the aetiology of neurodevelopmental disorders, and may be additionally disturbed in copy number variant syndromes. In this systematic review, the databases PubMed, Embase, and Scopus were searched for studies of excitation/inhibition imbalance in relation to neurodevelopmental disorders in human copy number variant samples. A total of 53 studies were included, representing a variety of copy number variants and research methodologies. The resulting data suggests excitation/inhibition balance is indeed disrupted in different copy number variant populations, providing insight into a putative mechanism of both idiopathic and genetic neurodevelopmental disorders. However, the high level of heterogeneity in the data set, alongside emerging techniques for excitation/inhibition assessment, prompts further investigation of this field.https://doi.org/10.1186/s11689-025-09614-8Neurodevelopmental disordersCopy number variationExcitationInhibitionGlutamateγ-aminobutyric acid
spellingShingle Amy L. Sylvester
Eva Hensenne
Dimo Ivanov
Benedikt A. Poser
David E. J. Linden
Thérèse van Amelsvoort
Claudia Vingerhoets
Neural excitation/inhibition imbalance and neurodevelopmental pathology in human copy number variant syndromes: a systematic review
Journal of Neurodevelopmental Disorders
Neurodevelopmental disorders
Copy number variation
Excitation
Inhibition
Glutamate
γ-aminobutyric acid
title Neural excitation/inhibition imbalance and neurodevelopmental pathology in human copy number variant syndromes: a systematic review
title_full Neural excitation/inhibition imbalance and neurodevelopmental pathology in human copy number variant syndromes: a systematic review
title_fullStr Neural excitation/inhibition imbalance and neurodevelopmental pathology in human copy number variant syndromes: a systematic review
title_full_unstemmed Neural excitation/inhibition imbalance and neurodevelopmental pathology in human copy number variant syndromes: a systematic review
title_short Neural excitation/inhibition imbalance and neurodevelopmental pathology in human copy number variant syndromes: a systematic review
title_sort neural excitation inhibition imbalance and neurodevelopmental pathology in human copy number variant syndromes a systematic review
topic Neurodevelopmental disorders
Copy number variation
Excitation
Inhibition
Glutamate
γ-aminobutyric acid
url https://doi.org/10.1186/s11689-025-09614-8
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