Medial Prefrontal Cortex Glutamate Is Reduced in Schizophrenia and Moderated by Measurement Quality: A Meta-analysis of Proton Magnetic Resonance Spectroscopy Studies.
Medial Prefrontal Cortex Glutamate Is Reduced in Schizophrenia and Moderated by Measurement Quality: A Meta-analysis of Proton Magnetic Resonance Spectroscopy Studies.
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DOI：
10.1016/j.biopsych.2021.06.008
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发表时间：
2021-11-01
影响因子：
10.6
通讯作者：
中科院分区：
文献类型：
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作者：
磁共振波谱学研究分别测量脑谷氨酸和谷氨酰胺有助于阐明精神分裂症的病理生理学。一个扩展的文献和改进的方法激发了一个更新的荟萃分析检查测量质量和其他调节因素的影响，在精神分裂症的谷氨酸水平异常的特点。检索先前的荟萃分析和MEDLINE数据库，确定了截至2020年3月25日发表的83个质子磁共振波谱数据集。提取了三个质量指标-Cramér-Rao下限（CRLB）、线宽和变异系数。采用随机效应、逆方差加权模型计算合并效应量（Hedges' g）。使用质量指标、场强、回波时间、药物、年龄和疾病阶段进行主持人分析。在36个数据集（2086名参与者）中，患者的内侧前额叶皮层谷氨酸盐显著降低（g =-0.19，CI =-0.07至-0.32）。CRLB和变异系数质量亚组显着缓和这种影响。在CRLB或变异系数较低的研究中，谷氨酸的降低幅度更大（分别为g = −0.44，CI = −0.29至−0.60和g = −0.43，CI = −0.29至−0.57）。使用回波时间≤20 ms的研究也显示谷氨酸盐的显著降低（g = −0.41，CI = −0.26至−0.55）。在11个海马数据集中，组间差异和调节效应不显著。丘脑和背外侧前额叶皮层的组效应也不显著。高质量的测量结果显示，精神分裂症患者的内侧前额叶皮层谷氨酸盐持续减少。更严格的CRLB标准和减少滋扰方差可能会增加未来研究的敏感性，检查其他地区和精神分裂症异常谷氨酸水平的病理生理意义。
Magnetic resonance spectroscopy studies measuring brain glutamate separately from glutamine are helping elucidate schizophrenia pathophysiology. An expanded literature and improved methodologies motivate an updated meta-analysis examining effects of measurement quality and other moderating factors in characterizing abnormal glutamate levels in schizophrenia. Searching previous meta-analyses and the MEDLINE database identified 83 proton magnetic resonance spectroscopy datasets published through March 25, 2020. Three quality metrics were extracted—Cramér–Rao lower bound (CRLB), line width, and coefficient of variation. Pooled effect sizes (Hedges’ g) were calculated with random-effects, inverse variance-weighted models. Moderator analyses were conducted using quality metrics, field strength, echo time, medication, age, and stage of illness. Across 36 datasets (2086 participants), medial prefrontal cortex glutamate was significantly reduced in patients (g = −0.19, confidence interval [CI] = −0.07 to −0.32). CRLB and coefficient of variation quality subgroups significantly moderated this effect. Glutamate was significantly more reduced in studies with lower CRLB or coefficient of variation (g = −0.44, CI = −0.29 to −0.60, and g = −0.43, CI = −0.29 to −0.57, respectively). Studies using echo time ≤20 ms also showed significantly greater reduction in glutamate (g = −0.41, CI = −0.26 to −0.55). Across 11 hippocampal datasets, group differences and moderator effects were nonsignificant. Group effects in thalamus and dorsolateral prefrontal cortex were also nonsignificant. High-quality measurements reveal consistently reduced medial prefrontal cortex glutamate in schizophrenia. Stricter CRLB criteria and reduced nuisance variance may increase the sensitivity of future studies examining additional regions and the pathophysiological significance of abnormal glutamate levels in schizophrenia.
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