BACKGROUND To date, there is no systematic overview of glutamate in the dorsolateral prefrontal cortex (DLPFC) of patients with schizophrenia. Here, we meta-analyzed case-control studies of high-field proton magnetic resonance spectroscopy (1H-MRS) investigating glutamate in DLPFC. Additionally, we estimated variance ratios to investigate homo/heterogeneity. METHODS Preregistration of the study was performed on September 20, 2019. The predefined literature search on PubMed comprised articles with search terms (magnetic resonance spectroscopy OR MRS) AND (glutamate OR glut∗ OR GLX) AND (schizophrenia OR psychosis OR schizophren∗). Meta-analyses with a fixed- and random-effects model with inverse variance method, DerSimonian-Laird estimator for τ2, and Cohen's d were calculated. For differences in variability, we calculated a random-effects model for measures of variance ratios. The primary study outcome was the difference in glutamate in the DLPFC in cases versus controls. Secondary outcomes were differences in variability. RESULTS The quantitative analysis comprised 429 cases and 365 controls. Overall, we found no group difference (d = 0.03 [95% confidence interval (CI), -0.20 to 0.26], z = 0.28, p = .78). Sensitivity analysis revealed an effect for medication status (Q = 8.35, p = .039), i.e., increased glutamate in antipsychotic-naïve patients (d = 0.46 [95% CI, 0.08 to 0.84], z = 2.37, p = .018). Concerning variance ratios, we found an effect of medication status (Q = 16.95, p < .001) due to lower coefficient of variation ratio (CVR) in medication-naïve patients (logCVR = -0.49 [95% CI, -0.78 to -0.20], z = -3.33, p < .001). In studies with medicated patients, we found higher CVR (logCVR = 0.22 [95% CI, 0.06 to 0.39], z = 2.67; p = .008). CONCLUSIONS We carefully interpret the higher levels and lower variability in cortical glutamate in antipsychotic-naïve patients as a possible key factor resulting from a putative allostatic mechanism. We conclude that care has to be taken when evaluating metabolite levels in clinical samples in which medication might confound findings.

中文翻译：

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精神分裂症患者背外侧前额叶皮层中的谷氨酸：1-HMRS 研究的荟萃分析。

背景迄今为止，还没有关于精神分裂症患者背外侧前额叶皮层 (DLPFC) 中谷氨酸的系统概述。在这里，我们对研究 DLPFC 中谷氨酸盐的高场质子磁共振波谱 (1H-MRS) 的病例对照研究进行了荟萃分析。此外，我们估计方差比以研究同质/异质性。方法 本研究的预注册于 2019 年 9 月 20 日进行。 PubMed 上的预定义文献搜索包括具有搜索词（磁共振波谱或 MRS）和（谷氨酸或谷氨酸或 GLX）和（精神分裂症或精神病或精神分裂症）的文章。使用具有逆方差方法的固定和随机效应模型、τ2 的 DerSimonian-Laird 估计量和 Cohen 的 d 进行荟萃分析。对于变异性的差异，我们计算了一个随机效应模型来衡量方差比。主要研究结果是病例与对照中 DLPFC 中谷氨酸的差异。次要结果是变异性的差异。结果 定量分析包括 429 例病例和 365 例对照。总体而言，我们没有发现组间差异（d = 0.03 [95% 置信区间 (CI)，-0.20 至 0.26]，z = 0.28，p = .78）。敏感性分析揭示了药物状态的影响（Q = 8.35，p = .039），即在未使用抗精神病药的患者中增加谷氨酸盐（d = 0.46 [95% CI，0.08 至 0.84]，z = 2.37，p = .018 ）。关于方差比，我们发现药物状态的影响（Q = 16.95，p < .001）由于未用药患者的变异系数 (CVR) 较低（logCVR = -0.49 [95% CI，-0.78 至 - 0.20]，z = -3.33，p < .001）。在对药物患者的研究中，我们发现更高的 CVR（logCVR = 0.22 [95% CI，0.06 至 0.39]，z = 2.67；p = .008）。结论 我们仔细解释了未使用抗精神病药的患者皮质谷氨酸的较高水平和较低的变异性，这可能是由推定的分配机制引起的一个关键因素。我们得出的结论是，在评估药物可能会混淆结果的临床样本中的代谢物水平时，必须小心谨慎。