Regionally Distinct Alterations in Membrane Phospholipid Metabolism in Schizophrenia: A Meta-analysis of Phosphorus Magnetic Resonance Spectroscopy Studies
Regionally Distinct Alterations in Membrane Phospholipid Metabolism in Schizophrenia: A Meta-analysis of Phosphorus Magnetic Resonance Spectroscopy Studies
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DOI：
10.1016/j.bpsc.2019.09.008
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发表时间：
2020-03-01
影响因子：
5.9
通讯作者：
Prasad, Konasale M.
中科院分区：
文献类型：
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作者：
Haszto, Connor S.;Stanley, Jeffrey A.;Prasad, Konasale M.
背景：关于精神分裂症膜磷脂代谢改变的现有数据多种多样。我们对磷磁共振波谱研究进行了荟萃分析，这是一种非侵入性成像方法，可以通过测量磷酸单酯 (PME) 和磷酸二酯 (PDE) 水平来评估皮质的分子生物化学，这可以提供精神分裂症神经毡膜扩张和收缩所涉及的生化过程改变的证据。方法：我们分析了来自 24 篇同行评审出版物的精神分裂症受试者额叶和颞叶的 PME 和 PDE 数据通过构建随机效应和固定效应模型，使用 R 中的 MAVIS 包。还评估了效应大小的异质性、发表偏倚的影响和文件抽屉分析。 结果：精神分裂症受试者的额叶区 PME 水平较低 (p = .008)，颞区 PDE 水平升高 (p < .001)，具有显着的异质性。我们注意到额叶 PME 和 PDE 以及时间 PDE 水平存在显着的发表偏差和文件抽屉效应，但时间 PME 水平则不然。自动防故障分析估计，需要大量的阴性研究才能提供无显着性的结果。结论：尽管存在方法学差异，这些磷磁共振波谱研究表明，与反映神经毡收缩的对照受试者相比，精神分裂症受试者中与神经毡相关的膜磷脂代谢存在区域特异性不平衡。具体来说，额叶区 PME 水平降低和颞区 PDE 水平升高分别提供了神经毡膜合成减少和降解增加的证据。尽管存在显着的异质性和发表偏倚，但仍需要大量的阴性研究才能使该荟萃分析的结果变得不显着。这些发现值得进一步的尸检和动物研究。
BACKGROUND: Existing data on altered membrane phospholipid metabolism in schizophrenia are diverse. We conducted a meta-analysis of studies of phosphorus magnetic resonance spectroscopy, a noninvasive imaging approach that can assess molecular biochemistry of cortex by measuring phosphomonoester (PME) and phosphodiester (PDE) levels, which can provide evidence of altered biochemical processes involved in neuropil membrane expansion and contraction in schizophrenia.METHODS: We analyzed PME and PDE data in the frontal and temporal lobes in subjects with schizophrenia from 24 peer-reviewed publications using the MAVIS package in R by building random- and fixed-effects models. Heterogeneity of effect sizes, effects of publication bias, and file drawer analysis were also assessed.RESULTS: Subjects with schizophrenia showed lower PME levels in the frontal regions (p = .008) and elevated PDE levels in the temporal regions (p < .001) with significant heterogeneity. We noted significant publication bias and file drawer effect for frontal PME and PDE and temporal PDE levels, but not for temporal PME levels. Fail-safe analysis estimated that a high number of negative studies were required to provide nonsignificant results.CONCLUSIONS: Despite methodological differences, these phosphorus magnetic resonance spectroscopy studies demonstrate regionally specific imbalance in membrane phospholipid metabolism related to neuropil in subjects with schizophrenia compared with control subjects reflecting neuropil contraction. Specifically, decreased PME levels in the frontal regions and elevated PDE levels in the temporal regions provide evidence of decreased synthesis and increased degradation of neuropil membrane, respectively. Notwithstanding significant heterogeneity and publication bias, a large number of negative studies are required to render the results of this meta-analysis nonsignificant. These findings warrant further postmortem and animal studies.