Glutamate in Schizophrenia: A Focused Review and Meta-Analysis of 1H-MRS Studies
Glutamate in Schizophrenia: A Focused Review and Meta-Analysis of 1H-MRS Studies
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DOI：
10.1093/schbul/sbr069
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发表时间：
2013-01-01
影响因子：
6.6
通讯作者：
Pol, Hilleke E. Hulshoff
中科院分区：
文献类型：
--
作者：
Marsman, Anouk;van den Heuvel, Martijn P.;Pol, Hilleke E. Hulshoff
精神分裂症是一种严重的慢性精神疾病，以幻觉和妄想为特征。在该疾病中观察到脑容量减少，尽管这些变化的起源尚不清楚。这与n-甲基-d-天冬氨酸（NMDA）受体介导的谷氨酸能神经传递的变化有关，因为假设精神分裂症中NMDA受体功能障碍导致谷氨酸释放增加，这可能具有兴奋毒性作用。然而，精神分裂症中谷氨酸代谢物变化的幅度和程度尚不清楚。利用H-1磁共振波谱（H-1- mrs），可以获得大脑中谷氨酸和谷氨酰胺浓度的体内信息。通过MEDLINE数据库进行了系统搜索，以确定相关的H-1-MRS研究，这些研究检测了精神分裂症患者和健康对照者之间谷氨酸和谷氨酰胺浓度的差异。共确定了28项研究，包括647名精神分裂症患者和608名健康对照者。对于每项研究，计算Cohen's d，并使用随机效应模型进行组分析的主效应。与健康个体相比，精神分裂症患者内侧额叶区谷氨酸降低，谷氨酰胺升高。按年龄分组的关联表明，与健康对照相比，精神分裂症患者的谷氨酸和谷氨酰胺浓度随年龄的增长下降得更快。这可能反映了精神分裂症的异常过程，如突触活性改变、谷氨酸受体功能改变、谷氨酰胺-谷氨酸循环异常或谷氨酸运输功能障碍。
Schizophrenia is a severe chronic psychiatric illness, characterized by hallucinations and delusions. Decreased brain volumes have been observed in the disease, although the origin of these changes is unknown. Changes in the n-methyl-d-aspartate (NMDA)-receptor mediated glutamatergic neurotransmission are implicated, since it is hypothesized that NMDA-receptor dysfunction in schizophrenia leads to increased glutamate release, which can have excitotoxic effects. However, the magnitude and extent of changes in glutamatergic metabolites in schizophrenia are not clear. With H-1 magnetic resonance spectroscopy (H-1-MRS), in vivo information about glutamate and glutamine concentrations can be obtained in the brain. A systematic search through the MEDLINE database was conducted to identify relevant H-1-MRS studies that examined differences in glutamate and glutamine concentrations between patients with schizophrenia and healthy control subjects. Twenty-eight studies were identified and included a total of 647 patients with schizophrenia and 608 healthy-control subjects. For each study, Cohen's d was calculated and main effects for group analyses were performed using the random-effects model. Medial frontal region glutamate was decreased and glutamine was increased in patients with schizophrenia as compared with healthy individuals. Group-by-age associations revealed that in patients with schizophrenia, glutamate and glutamine concentrations decreased at a faster rate with age as compared with healthy controls. This could reflect aberrant processes in schizophrenia, such as altered synaptic activity, changed glutamate receptor functioning, abnormal glutamine-glutamate cycling, or dysfunctional glutamate transport.