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

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.

• Authors: Emanuele Felice Osimo, Katherine Beck, Tiago Reis Marques, Oliver D Howes
• Journal: Molecular psychiatry (Mol Psychiatry) Vol. 24 Issue 4 Pg. 549-561 (04 2019) ISSN: 1476-5578 [Electronic] England
• PMID: 29511299 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't, Systematic Review)

Chemical References

• Disks Large Homolog 4 Protein
• RNA, Messenger
• SNAP25 protein, human
• Synapsins
• Synaptophysin
• Synaptosomal-Associated Protein 25
• rab3A GTP-Binding Protein

Topics

• 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)