Alterations in brain synaptic proteins and mRNAs in mood disorders: a systematic review and meta-analysis of postmortem brain studiesShow others and affiliations
2022 (English)In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 27, no 3, p. 1362-1372Article, review/survey (Refereed) Published
Abstract [en]
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.
Place, publisher, year, edition, pages
Springer Nature, 2022. Vol. 27, no 3, p. 1362-1372
National Category
Psychiatry
Identifiers
URN: urn:nbn:se:oru:diva-105499DOI: 10.1038/s41380-021-01410-9ISI: 000741938400001PubMedID: 35022529Scopus ID: 2-s2.0-85122763438OAI: oai:DiVA.org:oru-105499DiVA, id: diva2:1750211
Note
Funding agencies:
United States Department of Health & Human Services
National Institutes of Health (NIH) - USA 1R21MH119441-01A1
SAMHSA 6H79FG000470-01M003
University of Texas Health Science center at Houston (UTHealth)
2023-04-122023-04-122023-04-12Bibliographically approved