TY - JOUR
T1 - Alterations in brain synaptic proteins and mRNAs in mood disorders
T2 - a systematic review and meta-analysis of postmortem brain studies
AU - Leung, Edison
AU - Lau, Ethan W.
AU - Liang, Andi
AU - de Dios, Constanza
AU - Suchting, Robert
AU - Östlundh, Linda
AU - Masdeu, Joseph C.
AU - Fujita, Masahiro
AU - Sanches, Marsal
AU - Soares, Jair C.
AU - Selvaraj, Sudhakar
N1 - Funding Information:
SS has received grants/research support from NIH R21 (1R21MH119441-01A1) and SAMHSA (6H79FG000470-01M003). The University of Texas Health Science center at Houston (UTHealth) faculty research supplement funds (SS) were utilized for this study. The institution played no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Funding Information:
JCS has received grants/research support from BMS, Forrest, J&J, Merck, Compass pathways, Stanley Medical Research Institute, NIH and has been a speaker for Pfizer and Abbott. SS has received speaking honoraria from Global Medical Education and honoraria from British Medical Journal Publishing Group; own shares at Flow Med Tech. Research support from Compass pathways, Liva Nova and Janssen. All the other authors have no competing interests to disclose.
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2022
Y1 - 2022
N2 - Abstract: The pathophysiological mechanisms underlying bipolar (BD) and major depressive disorders (MDD) are multifactorial but likely involve synaptic dysfunction and dysregulation. There are multiple synaptic proteins but three synaptic proteins, namely SNAP-25, PSD-95, and synaptophysin, have been widely studied for their role in synaptic function in human brain postmortem studies in BD and MDD. These studies have yielded contradictory results, possibly due to the small sample size and sourcing material from different cortical regions of the brain. We performed a systematic review and meta-analysis to understand the role of these three synaptic proteins and other synaptic proteins, messenger RNA (mRNA) and their regional localizations in BD and MDD. A systematic literature search was conducted and the review is reported in accordance with the MOOSE Guidelines. Meta-analysis was performed to compare synaptic marker levels between BD/MDD groups and controls separately. 1811 papers were identified in the literature search and screened against the preset inclusion and exclusion criteria. A total of 72 studies were screened in the full text, of which 47 were identified as eligible to be included in the systematic review. 24 of these 47 papers were included in the meta-analysis. The meta-analysis indicated that SNAP-25 protein levels were significantly lower in BD. On average, PSD-95 mRNA levels were lower in BD, and protein levels of SNAP-25, PSD-95, and syntaxin were lower in MDD. Localization analysis showed decreased levels of PSD-95 protein in the frontal cortex. We found specific alterations in synaptic proteins and RNAs in both BD and MDD. The review was prospectively registered online in PROSPERO international prospective register of systematic reviews, registration no. CRD42020196932.
AB - Abstract: The pathophysiological mechanisms underlying bipolar (BD) and major depressive disorders (MDD) are multifactorial but likely involve synaptic dysfunction and dysregulation. There are multiple synaptic proteins but three synaptic proteins, namely SNAP-25, PSD-95, and synaptophysin, have been widely studied for their role in synaptic function in human brain postmortem studies in BD and MDD. These studies have yielded contradictory results, possibly due to the small sample size and sourcing material from different cortical regions of the brain. We performed a systematic review and meta-analysis to understand the role of these three synaptic proteins and other synaptic proteins, messenger RNA (mRNA) and their regional localizations in BD and MDD. A systematic literature search was conducted and the review is reported in accordance with the MOOSE Guidelines. Meta-analysis was performed to compare synaptic marker levels between BD/MDD groups and controls separately. 1811 papers were identified in the literature search and screened against the preset inclusion and exclusion criteria. A total of 72 studies were screened in the full text, of which 47 were identified as eligible to be included in the systematic review. 24 of these 47 papers were included in the meta-analysis. The meta-analysis indicated that SNAP-25 protein levels were significantly lower in BD. On average, PSD-95 mRNA levels were lower in BD, and protein levels of SNAP-25, PSD-95, and syntaxin were lower in MDD. Localization analysis showed decreased levels of PSD-95 protein in the frontal cortex. We found specific alterations in synaptic proteins and RNAs in both BD and MDD. The review was prospectively registered online in PROSPERO international prospective register of systematic reviews, registration no. CRD42020196932.
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U2 - 10.1038/s41380-021-01410-9
DO - 10.1038/s41380-021-01410-9
M3 - Review article
AN - SCOPUS:85122763438
JO - Molecular Psychiatry
JF - Molecular Psychiatry
SN - 1359-4184
ER -