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Neuroimaging in schizophrenia: an overview of findings and their implications for synaptic changes

Howes, Oliver D; Cummings, Connor; Chapman, George E; Shatalina, Ekaterina; (2023) Neuroimaging in schizophrenia: an overview of findings and their implications for synaptic changes. Neuropsychopharmacology , 48 pp. 151-167. 10.1038/s41386-022-01426-x. Green open access

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Abstract

Over the last five decades, a large body of evidence has accrued for structural and metabolic brain alterations in schizophrenia. Here we provide an overview of these findings, focusing on measures that have traditionally been thought to reflect synaptic spine density or synaptic activity and that are relevant for understanding if there is lower synaptic density in the disorder. We conducted literature searches to identify meta-analyses or other relevant studies in patients with chronic or first-episode schizophrenia, or in people at high genetic or clinical risk for psychosis. We identified 18 meta-analyses including over 50,000 subjects in total, covering: structural MRI measures of gyrification index, grey matter volume, grey matter density and cortical thickness, neurite orientation dispersion and density imaging, PET imaging of regional glucose metabolism and magnetic resonance spectroscopy measures of N-acetylaspartate. We also review preclinical evidence on the relationship between ex vivo synaptic measures and structural MRI imaging, and PET imaging of synaptic protein 2A (SV2A). These studies show that schizophrenia is associated with lower grey matter volumes and cortical thickness, accelerated grey matter loss over time, abnormal gyrification patterns, and lower regional SV2A levels and metabolic markers in comparison to controls (effect sizes from ~ −0.11 to −1.0). Key regions affected include frontal, anterior cingulate and temporal cortices and the hippocampi. We identify several limitations for the interpretation of these findings in terms of understanding synaptic alterations. Nevertheless, taken with post-mortem findings, they suggest that schizophrenia is associated with lower synaptic density in some brain regions. However, there are several gaps in evidence, in particular whether SV2A findings generalise to other cohorts.

Type: Article
Title: Neuroimaging in schizophrenia: an overview of findings and their implications for synaptic changes
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41386-022-01426-x
Publisher version: https://doi.org/10.1038/s41386-022-01426-x
Language: English
Additional information: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry
URI: https://discovery.ucl.ac.uk/id/eprint/10176820
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