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PMID: 29511299 Published · ppublish English Journal Article Meta-Analysis Research Support, Non-U.S. Gov't Systematic Review

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

Molecular psychiatry ·Vol. 24 ·No. 4 ·2019-00-00 ·Pages 549-561

Osimo EF, Beck K, Reis Marques T, Howes OD

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.

MeSH Terms
Adult Brain/metabolism Case-Control Studies Disks Large Homolog 4 Protein/metabolism Female Gyrus Cinguli/metabolism Hippocampus/metabolism Humans Male Middle Aged RNA, Messenger/metabolism Schizophrenia/genetics,physiopathology Synapses/genetics,metabolism Synapsins/metabolism Synaptic Vesicles/metabolism Synaptophysin/genetics,metabolism Synaptosomal-Associated Protein 25/metabolism Temporal Lobe/metabolism rab3A GTP-Binding Protein/metabolism
Chemicals
Disks Large Homolog 4 Protein RNA, Messenger SNAP25 protein, human Synapsins Synaptophysin Synaptosomal-Associated Protein 25 rab3A GTP-Binding Protein
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Osimo Emanuele Felice ORCID
Psychiatric Imaging Group, MRC London Institute of Medical Sciences, Hammersmith Hospital, Imperial College London, London, UK. | Psychiatric Imaging Group, Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, UK. | Department of Psychiatry, University of Cambridge, Cambridge, UK. | Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK.
Beck Katherine
Psychiatric Imaging Group, MRC London Institute of Medical Sciences, Hammersmith Hospital, Imperial College London, London, UK. | Psychiatric Imaging Group, Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, UK. | Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. | South London and Maudsley NHS Foundation Trust, Camberwell, London, UK.
Reis Marques Tiago
Psychiatric Imaging Group, MRC London Institute of Medical Sciences, Hammersmith Hospital, Imperial College London, London, UK. | Psychiatric Imaging Group, Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, UK. | Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. | South London and Maudsley NHS Foundation Trust, Camberwell, London, UK.
Howes Oliver D
Psychiatric Imaging Group, MRC London Institute of Medical Sciences, Hammersmith Hospital, Imperial College London, London, UK. [email protected]. | Psychiatric Imaging Group, Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, UK. [email protected]. | Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. [email protected]. | South London and Maudsley NHS Foundation Trust, Camberwell, London, UK. [email protected].
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Article Info
Journal
Molecular psychiatry
Abbr.
Mol Psychiatry
ISSN
1476-5578
DOI
10.1038/s41380-018-0041-5
Email
[email protected]
Published
2019-00-00
Epub
2018-00-06
Pages
549-561
Language
English
Region
England
NLM ID
9607835
PMCID
PMC6004314
Subset
IM
Grants
Wellcome Trust · United Kingdom
Medical Research Council · G0700995 · United Kingdom
Medical Research Council · MC_U120097115 · United Kingdom
External Links
PubMed source DOI: 10.1038/s41380-018-0041-5 PMC Full Text View journal details
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