Synaptic loss in schizophrenia: a meta-analysis and systematic review of synaptic protein and mRNA measures

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Title: Synaptic loss in schizophrenia: a meta-analysis and systematic review of synaptic protein and mRNA measures
Authors: Osimo, E
Beck, K
Reis Marques, T
Howes, OD
Item Type: Journal Article
Abstract: Although synaptic loss is thought to be core to the pathophysiology of schizophrenia, the nature, consistency and magnitude of synaptic protein and mRNA changes has not been systematically appraised. Our objective was thus to systematically review and meta-analyse findings. The entire PubMed database was searched for studies from inception date to the 1st of July 2017. We selected case-control postmortem studies in schizophrenia quantifying synaptic protein or mRNA levels in brain tissue. The difference in protein and mRNA levels between cases and controls was extracted and meta-analysis conducted. Among the results, we found a significant reduction in synaptophysin in schizophrenia in the hippocampus (effect size: −0.65, p < 0.01), frontal (effect size: −0.36, p = 0.04), and cingulate cortices (effect size: −0.54, p = 0.02), but no significant changes for synaptophysin in occipital and temporal cortices, and no changes for SNAP-25, PSD-95, VAMP, and syntaxin in frontal cortex. There were insufficient studies for meta-analysis of complexins, synapsins, rab3A and synaptotagmin and mRNA measures. Findings are summarised for these, which generally show reductions in SNAP-25, PSD-95, synapsin and rab3A protein levels in the hippocampus but inconsistency in other regions. Our findings of moderate–large reductions in synaptophysin in hippocampus and frontal cortical regions, and a tendency for reductions in other pre- and postsynaptic proteins in the hippocampus are consistent with models that implicate synaptic loss in schizophrenia. However, they also identify potential differences between regions and proteins, suggesting synaptic loss is not uniform in nature or extent.
Issue Date: 6-Mar-2018
Date of Acceptance: 31-Jan-2018
ISSN: 1359-4184
Publisher: Nature Publishing Group
Journal / Book Title: Molecular Psychiatry
Copyright Statement: © 2018 The Author(s). his 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
Sponsor/Funder: Commission of the European Communities
Funder's Grant Number: 607616
Keywords: 11 Medical And Health Sciences
06 Biological Sciences
17 Psychology And Cognitive Sciences
Publication Status: Published online
Online Publication Date: 2018-03-06
Appears in Collections:Clinical Sciences
Imaging Sciences
Faculty of Medicine

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