Department of Psychiatry, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, The Netherlands.
Department of Translational Neuroscience, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, The Netherlands.
Schizophr Bull. 2020 Feb 26;46(2):374-386. doi: 10.1093/schbul/sbz060.
Changed synapse density has been suggested to be involved in the altered brain connectivity underlying schizophrenia (SCZ) pathology. However, postmortem studies addressing this topic are heterogeneous and it is not known whether changes are restricted to specific brain regions. Using meta-analysis, we systematically and quantitatively reviewed literature on the density of postsynaptic elements in postmortem brain tissue of patients with SCZ compared to healthy controls. We included 3 outcome measurements for postsynaptic elements: dendritic spine density (DSD), postsynaptic density (PSD) number, and PSD protein expression levels. Random-effects meta-analysis (31 studies) revealed an overall decrease in density of postsynaptic elements in SCZ (Hedges's g: -0.33; 95% CI: -0.60 to -0.05; P = .020). Subgroup analyses showed reduction of postsynaptic elements in cortical but not subcortical tissues (Hedges's g: -0.44; 95% CI: -0.76 to -0.12; P = .008, Hedges's g: -0.11; 95% CI: -0.54 to 0.35; P = .671) and specifically a decrease for the outcome measure DSD (Hedges's g: -0.81; 95% CI: -1.37 to -0.26; P = .004). Further exploratory analyses showed a significant decrease of postsynaptic elements in the prefrontal cortex and cortical layer 3. In all analyses, substantial heterogeneity was present. Meta-regression analyses showed no influence of age, sex, postmortem interval, or brain bank on the effect size. This meta-analysis shows a region-specific decrease in the density of postsynaptic elements in SCZ. This phenotype provides an important cellular hallmark for future preclinical and neuropathological research in order to increase our understanding of brain dysconnectivity in SCZ.
突触密度的改变被认为与精神分裂症（SCZ）病理基础下大脑连接的改变有关。然而，针对这一主题的尸检研究存在异质性，目前尚不清楚这些变化是否仅限于特定的大脑区域。本研究采用荟萃分析的方法，系统地定量综述了精神分裂症患者死后脑组织中突触后成分密度的相关文献，并与健康对照组进行比较。我们纳入了 3 种突触后成分的测量结果：树突棘密度（DSD）、突触后密度（PSD）数量和 PSD 蛋白表达水平。随机效应荟萃分析（31 项研究）显示，精神分裂症患者的突触后成分密度总体下降（Hedges's g：-0.33；95%CI：-0.60 至-0.05；P =.020）。亚组分析显示，皮质而非皮质下组织的突触后成分减少（Hedges's g：-0.44；95%CI：-0.76 至-0.12；P =.008，Hedges's g：-0.11；95%CI：-0.54 至 0.35；P =.671），特别是 DSD 这一测量结果（Hedges's g：-0.81；95%CI：-1.37 至-0.26；P =.004）。进一步的探索性分析显示，前额叶皮层和皮层 3 层的突触后成分明显减少。在所有分析中，都存在显著的异质性。元回归分析显示，年龄、性别、尸检间隔或脑库对效应大小没有影响。本荟萃分析显示，精神分裂症患者的突触后成分密度存在特定的区域减少。这种表型为未来的临床前和神经病理学研究提供了一个重要的细胞标志，以增加我们对精神分裂症大脑连接异常的理解。
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