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.

中文翻译：

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精神分裂症的突触病理学：死后脑研究中突触后元素的荟萃分析。

已经暗示改变的突触密度与精神分裂症（SCZ）病理基础的改变的脑连通性有关。但是，针对该主题的事后研究是异类的，尚不清楚变化是否仅限于特定的大脑区域。使用荟萃分析，我们系统地和定量地回顾了与健康对照相比，SCZ患者死后脑组织中突触后元素密度的文献。我们对突触后元件包括3个结果测量值：树突棘密度（DSD），突触后密度（PSD）数和PSD蛋白表达水平。随机效应荟萃分析（31项研究）显示，SCZ中突触后元素的密度总体下降（Hedges的g：-0.33； 95％CI：-0.60至-0.05； P = .020）。亚组分析显示皮质中但非皮质下组织中突触后元素减少（Hedges's g：-0.44; 95％CI：-0.76至-0.12; P = .008，Hedges's g：-0.11; 95％CI：-0.54 to 0.35; P = .671），尤其是结果测量值DSD的降低（Hedges's g：-0.81； 95％CI：-1.37至-0.26； P = .004）。进一步的探索性分析表明前额叶皮层和皮质层3中的突触后元素明显减少。在所有分析中，均存在明显的异质性。荟萃回归分析显示，年龄，性别，验尸间隔或脑库对效应量没有影响。这项荟萃分析显示了SCZ中突触后元素密度的特定区域降低。