Synaptic loss in schizophrenia: a meta-analysis and systematic review of synaptic protein and mRNA measures
File(s)
Published version
Author(s)
Osimo, E
Beck, Katherine
Reis Marques, Tiago
Howes, Olived D
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.
Date Issued
2019-04-01
Date Acceptance
2018-01-31
Citation
Molecular Psychiatry, 2019, 24, pp.549-561
ISSN
1359-4184
Publisher
Nature Publishing Group
Start Page
549
End Page
561
Journal / Book Title
Molecular Psychiatry
Volume
24
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 http://creativecommons.org/licenses/by/4.0/.
Sponsor
Commission of the European Communities
Grant Number
607616
Subjects
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Neurosciences
Psychiatry
Neurosciences & Neurology
DORSOLATERAL PREFRONTAL CORTEX
ANTERIOR CINGULATE CORTEX
SYNAPTOPHYSIN GENE-EXPRESSION
MOSSY FIBER SYNAPSES
MEDIAL TEMPORAL-LOBE
BIPOLAR DISORDER
HIPPOCAMPAL VOLUME
FRONTAL-CORTEX
DECREASED EXPRESSION
POSTMORTEM BRAIN
Psychiatry
11 Medical and Health Sciences
06 Biological Sciences
17 Psychology and Cognitive Sciences
Publication Status
Published
Date Publish Online
2018-03-06