Centre for Mental Health, Swinburne University of Technology, Melbourne, VIC, Australia.
Molecular Psychiatry Laboratory, The Florey Institute of Neuroscience and Mental Health, Melbourne, VIC, Australia.
Aust N Z J Psychiatry. 2024 Nov;58(11):930-951. doi: 10.1177/00048674241254216. Epub 2024 May 29.
Studies using proton magnetic resonance spectroscopy reveal substantial inconsistencies in the levels of brain glutamate, glutamine and glutamate + glutamine across schizophrenia spectrum disorders. This systematic review employs qualitative and quantitative methods to analyse the patterns and relationships between glutamatergic metabolites, schizophrenia spectrum disorders and brain regions.
A literature search was conducted using various databases with keywords including glutamate, glutamine, schizophrenia, psychosis and proton magnetic resonance spectroscopy. Inclusion criteria were limited to case-control studies that reported glutamatergic metabolite levels in adult patients with a schizophrenia spectrum disorder diagnosis - i.e. first-episode psychosis, schizophrenia, treatment-resistant schizophrenia and/or ultra-treatment-resistant schizophrenia - using proton magnetic resonance spectroscopy at 3 T or above. Pooled study data were synthesized and analysed.
A total of 92 studies met the inclusion criteria, including 2721 healthy controls and 2822 schizophrenia spectrum disorder participants. Glu levels were higher in the basal ganglia, frontal cortex and medial prefrontal of first-episode psychosis participants, contrasting overall lower levels in schizophrenia participants. For Gln, strong differences in metabolite levels were evident in the basal ganglia, dorsolateral prefrontal cortex and frontal cortex, with first-episode psychosis showing significantly higher levels in the basal ganglia. In glutamate + glutamine, higher metabolite levels were found across schizophrenia spectrum disorder groups, particularly in the basal ganglia and dorsolateral prefrontal cortex of treatment-resistant schizophrenia participants. Significant relationships were found between metabolite levels and medication status, clinical measures and methodological variables.
The review highlights abnormal glutamatergic metabolite levels throughout schizophrenia spectrum disorders and in specific brain regions. The review underscores the importance of standardized future research assessing glutamatergic metabolites using proton magnetic resonance spectroscopy due to considerable literature heterogeneity.
使用质子磁共振波谱研究揭示了精神分裂症谱系障碍患者大脑谷氨酸、谷氨酰胺和谷氨酸+谷氨酰胺水平存在实质性的不一致。本系统评价采用定性和定量方法分析谷氨酸代谢物、精神分裂症谱系障碍和脑区之间的模式和关系。
使用各种数据库进行文献检索，关键词包括谷氨酸、谷氨酰胺、精神分裂症、精神病和质子磁共振波谱。纳入标准仅限于使用质子磁共振波谱在 3T 或更高场强下报告成年精神分裂症谱系障碍患者（即首发精神病、精神分裂症、难治性精神分裂症和/或超难治性精神分裂症）谷氨酸代谢物水平的病例对照研究。综合和分析汇总研究数据。
共有 92 项研究符合纳入标准，包括 2721 名健康对照者和 2822 名精神分裂症谱系障碍参与者。首发精神病患者的基底节、额叶和内侧前额叶的 Glu 水平较高，而精神分裂症患者的总体水平较低。对于 Gln，代谢物水平的差异在基底节、背外侧前额叶皮质和额叶皮质中非常明显，首发精神病患者的基底节中 Gln 水平明显较高。在谷氨酸+谷氨酰胺中，精神分裂症谱系障碍组的代谢物水平较高，尤其是在难治性精神分裂症患者的基底节和背外侧前额叶皮质中。还发现代谢物水平与药物状态、临床指标和方法学变量之间存在显著关系。
该综述强调了在精神分裂症谱系障碍和特定脑区中谷氨酸代谢物水平异常的重要性。由于文献异质性较大，该综述强调了使用质子磁共振波谱评估谷氨酸代谢物的未来标准化研究的重要性。
