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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...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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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. |
format | Online Article Text |
id | pubmed-8929434 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT halljeremy schizophreniagenomicsconvergenceonsynapticdevelopmentadultsynapticplasticityorboth AT braynicholasj schizophreniagenomicsconvergenceonsynapticdevelopmentadultsynapticplasticityorboth |