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Schizophrenia Genomics: Convergence on Synaptic Development, Adult Synaptic Plasticity, or Both?

Large-scale genomic studies of schizophrenia have identified hundreds of genetic loci conferring risk to the disorder. This progress offers an important route toward defining the biological basis of the condition and potentially developing new treatments. In this review, we discuss insights from rec...

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Detalles Bibliográficos
Autores principales: Hall, Jeremy, Bray, Nicholas J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8929434/
https://www.ncbi.nlm.nih.gov/pubmed/34974922
http://dx.doi.org/10.1016/j.biopsych.2021.10.018
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author Hall, Jeremy
Bray, Nicholas J.
author_facet Hall, Jeremy
Bray, Nicholas J.
author_sort Hall, Jeremy
collection PubMed
description Large-scale genomic studies of schizophrenia have identified hundreds of genetic loci conferring risk to the disorder. This progress offers an important route toward defining the biological basis of the condition and potentially developing new treatments. In this review, we discuss insights from recent genome-wide association study, copy number variant, and exome sequencing analyses of schizophrenia, together with functional genomics data from the pre- and postnatal brain, in relation to synaptic development and function. These data provide strong support for the view that synaptic dysfunction within glutamatergic and GABAergic (gamma-aminobutyric acidergic) neurons of the cerebral cortex, hippocampus, and other limbic structures is a central component of schizophrenia pathophysiology. Implicated genes and functional genomic data suggest that disturbances in synaptic connectivity associated with susceptibility to schizophrenia begin in utero but continue throughout development, with some alleles conferring risk to the disorder through direct effects on synaptic function in adulthood. This model implies that novel interventions for schizophrenia could include broad preventive approaches aimed at enhancing synaptic health during development as well as more targeted treatments aimed at correcting synaptic function in affected adults.
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spelling pubmed-89294342022-04-15 Schizophrenia Genomics: Convergence on Synaptic Development, Adult Synaptic Plasticity, or Both? Hall, Jeremy Bray, Nicholas J. Biol Psychiatry Review Large-scale genomic studies of schizophrenia have identified hundreds of genetic loci conferring risk to the disorder. This progress offers an important route toward defining the biological basis of the condition and potentially developing new treatments. In this review, we discuss insights from recent genome-wide association study, copy number variant, and exome sequencing analyses of schizophrenia, together with functional genomics data from the pre- and postnatal brain, in relation to synaptic development and function. These data provide strong support for the view that synaptic dysfunction within glutamatergic and GABAergic (gamma-aminobutyric acidergic) neurons of the cerebral cortex, hippocampus, and other limbic structures is a central component of schizophrenia pathophysiology. Implicated genes and functional genomic data suggest that disturbances in synaptic connectivity associated with susceptibility to schizophrenia begin in utero but continue throughout development, with some alleles conferring risk to the disorder through direct effects on synaptic function in adulthood. This model implies that novel interventions for schizophrenia could include broad preventive approaches aimed at enhancing synaptic health during development as well as more targeted treatments aimed at correcting synaptic function in affected adults. Elsevier 2022-04-15 /pmc/articles/PMC8929434/ /pubmed/34974922 http://dx.doi.org/10.1016/j.biopsych.2021.10.018 Text en © 2021 Society of Biological Psychiatry. https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Hall, Jeremy
Bray, Nicholas J.
Schizophrenia Genomics: Convergence on Synaptic Development, Adult Synaptic Plasticity, or Both?
title Schizophrenia Genomics: Convergence on Synaptic Development, Adult Synaptic Plasticity, or Both?
title_full Schizophrenia Genomics: Convergence on Synaptic Development, Adult Synaptic Plasticity, or Both?
title_fullStr Schizophrenia Genomics: Convergence on Synaptic Development, Adult Synaptic Plasticity, or Both?
title_full_unstemmed Schizophrenia Genomics: Convergence on Synaptic Development, Adult Synaptic Plasticity, or Both?
title_short Schizophrenia Genomics: Convergence on Synaptic Development, Adult Synaptic Plasticity, or Both?
title_sort schizophrenia genomics: convergence on synaptic development, adult synaptic plasticity, or both?
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8929434/
https://www.ncbi.nlm.nih.gov/pubmed/34974922
http://dx.doi.org/10.1016/j.biopsych.2021.10.018
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