Schizophrenia genomics: convergence on synaptic development, adult synaptic plasticity, or both?

Hall, Jeremy ORCID: https://orcid.org/0000-0003-2737-9009 and Bray, Nicholas J. ORCID: https://orcid.org/0000-0002-4357-574X 2022. Schizophrenia genomics: convergence on synaptic development, adult synaptic plasticity, or both? Biological Psychiatry 91 (8) , pp. 709-717. 10.1016/j.biopsych.2021.10.018

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Abstract

Large-scale genomic studies of schizophrenia have identified hundreds of genetic loci conferring risk to the disorder. This progress offers an important route towards defining the biological basis of the condition and potentially developing new treatments. In this review, we discuss insights from recent genome-wide association study (GWAS), copy number variant (CNV) and exome sequencing analyses of schizophrenia, together with functional genomics data from the pre- and post-natal brain, in relation to synaptic development and function. These data provide strong support for the view that synaptic dysfunction within glutamatergic and GABAergic 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 preventative approaches aimed at enhancing synaptic health during development as well as more targeted treatments aimed at correcting synaptic function in affected adults.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Neuroscience and Mental Health Research Institute (NMHRI) MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Additional Information:	This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Publisher:	Elsevier
ISSN:	0006-3223
Funders:	MRC
Date of First Compliant Deposit:	3 November 2021
Date of Acceptance:	23 October 2021
Last Modified:	11 May 2023 17:24
URI:	https://orca.cardiff.ac.uk/id/eprint/145275

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