Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Psychiatry and Psychotherapy CCM, Berlin, Germany; Berlin Institute of Health, Berlin, Germany.
Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Psychiatry and Psychotherapy CCM, Berlin, Germany.
Biol Psychiatry. 2021 Feb 1;89(3):270-277. doi: 10.1016/j.biopsych.2020.09.001. Epub 2020 Sep 8.
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 (H-MRS) investigating glutamate in DLPFC. Additionally, we estimated variance ratios to investigate homo/heterogeneity.
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 τ, 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.
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).
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.
迄今为止，尚无关于精神分裂症患者外侧前额叶皮质（DLPFC）谷氨酸的系统综述。在这里，我们对使用高磁场质子磁共振波谱（H-MRS）研究 DLPFC 谷氨酸的病例对照研究进行了荟萃分析。此外，我们还估计了方差比，以研究同型/异型。
该研究于 2019 年 9 月 20 日进行了预先注册。在 PubMed 上进行的预定文献检索包括使用搜索词（磁共振波谱或 MRS）和（谷氨酸或谷氨酰胺或 GLX）和（精神分裂症或精神病或精神分裂症）的文章。使用固定效应和随机效应模型、逆方差法、DerSimonian-Laird 估计τ和 Cohen's d 计算荟萃分析。对于变异性的差异，我们计算了方差比的随机效应模型。主要研究结果是病例与对照组 DLPFC 谷氨酸的差异。次要结果是变异性的差异。
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=0.78）。敏感性分析显示药物状态的影响（Q=8.35，p=0.039），即抗精神病药初治患者谷氨酸增加（d=0.46 [95%CI，0.08 至 0.84]，z=2.37，p=0.018）。关于方差比，我们发现药物状态的影响（Q=16.95，p<.001），这是由于初治患者的变异系数比（CVR）较低（logCVR=-0.49 [95%CI，-0.78 至-0.20]，z=-3.33，p<.001）。在接受药物治疗的患者中，我们发现 CVR 更高（logCVR=0.22 [95%CI，0.06 至 0.39]，z=2.67；p=0.008）。
我们谨慎地解释了抗精神病药初治患者皮质谷氨酸水平升高和变异性降低，这可能是一种由所谓的适应机制导致的关键因素。我们的结论是，在评估可能使发现复杂化的临床样本中的代谢物水平时，必须谨慎。
