Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Internal address A.01.126, PO Box 85500, 3508 GA Utrecht, The Netherlands.
Schizophr Bull. 2013 Jan;39(1):120-9. doi: 10.1093/schbul/sbr069. Epub 2011 Jul 11.
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 (1)H magnetic resonance spectroscopy ((1)H-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 (1)H-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.
精神分裂症是一种严重的慢性精神疾病，其特征为幻觉和妄想。研究发现，该病患者的大脑体积减小，但其病变的起源尚不清楚。有研究表明，N-甲基-D-天冬氨酸（NMDA）受体介导的谷氨酸能神经传递发生变化与精神分裂症有关，因为精神分裂症中 NMDA 受体功能障碍可能导致谷氨酸释放增加，从而产生兴奋性毒性。然而，精神分裂症患者谷氨酸代谢物的变化幅度和范围尚不清楚。通过 1H 磁共振波谱（1H-MRS）可以在大脑中获得关于谷氨酸和谷氨酰胺浓度的活体信息。通过对 MEDLINE 数据库进行系统检索，确定了检查精神分裂症患者与健康对照组之间谷氨酸和谷氨酰胺浓度差异的相关 1H-MRS 研究。共确定了 28 项研究，这些研究共纳入了 647 名精神分裂症患者和 608 名健康对照者。对每项研究均计算了 Cohen's d，并使用随机效应模型对组间分析的主要效应进行了分析。与健康个体相比，精神分裂症患者的内侧额区谷氨酸减少，谷氨酰胺增加。组间与年龄的关联分析表明，与健康对照组相比，精神分裂症患者的谷氨酸和谷氨酰胺浓度随年龄的增加而更快下降。这可能反映了精神分裂症中的异常过程，如突触活动改变、谷氨酸受体功能改变、谷氨酰胺-谷氨酸循环异常或谷氨酸转运功能障碍。
