双相(BD)和重度抑郁症(MDD)的病理生理机制是多因素的,但可能涉及突触功能障碍和失调。有多种突触蛋白,但有三种突触蛋白,即SNAP-25、PSD-95和突触素,在BD和MDD的人脑事后研究中,它们在突触功能中的作用已得到广泛研究。这些研究产生了相互矛盾的结果,可能是由于样本量小,并且从大脑的不同皮质区域采购材料。我们进行了系统评价和荟萃分析,以了解这三种突触蛋白和其他突触蛋白的作用,信使RNA(mRNA)及其在BD和MDD中的区域定位。进行了系统的文献检索,并根据MOOSE指南报告了该综述。进行Meta分析,比较BD/MDD组和对照组之间的突触标志物水平。在文献检索中确定了1811篇论文,并根据预设的纳入和排除标准进行了筛选。全文共筛选了72项研究,其中47人被确定有资格被纳入系统审查。这47篇论文中有24篇被纳入荟萃分析。荟萃分析表明,BD中的SNAP-25蛋白水平显着降低。平均而言,BD中PSD-95mRNA水平较低,MDD中SNAP-25,PSD-95和syntaxin的蛋白质水平较低。定位分析显示额叶皮质中PSD-95蛋白水平降低。我们发现BD和MDD中突触蛋白和RNA的特定变化。该评论已在PROSPERO国际系统评论前瞻性注册网上注册,登记号CRD42020196932。
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.