Abnormal Concentration of GABA and Glutamate in The Prefrontal Cortex in Schizophrenia.-An in Vivo 1H-MRS Study.
Abnormal Concentration of GABA and Glutamate in The Prefrontal Cortex in Schizophrenia.-An in Vivo 1H-MRS Study.
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DOI：
10.11919/j.issn.1002-0829.217004
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发表时间：
2017-10-25
期刊：
影响因子：
--
通讯作者：
Liu D
中科院分区：
文献类型：
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作者：
Chen T;Wang Y;Zhang J;Wang Z;Xu J;Li Y;Yang Z;Liu D
精神分裂症的病因和病理机制尚不清楚。传统的多巴胺（DA）假说不能完全解释其病理和治疗。谷氨酸（Glu）和γ-氨基丁酸（GABA）假说表明，精神分裂症患者的大脑中谷氨酸（Glu）或氨基丁酸（GABA）浓度异常。磁共振波谱（MRS）显示，精神分裂症患者腹内侧前额叶皮层（vmPFC）包括前扣带皮层（ACC）的谷氨酸水平升高。探讨谷氨酸系统（谷氨酸和γ-氨基丁酸）在精神分裂症发病机制中的作用。24例精神分裂症药物naïve患者与24名健康志愿者按性别、年龄、文化程度进行匹配。采用西门子3T MRI系统采集受试者的磁共振波谱（MRS）数据。感兴趣的区域包括左背外侧前额叶皮层（IDLPFC），腹内侧前额叶皮层（vmPFC）和前扣带皮层（ACC）。利用LCModel软件分析目标区域γ-氨基丁酸（GABA）、谷氨酸（Glu）、谷氨酰胺（Gln）、n -乙酰天冬氨酸（NAA）、n -乙酰天冬氨酸谷氨酸（NAAG）的浓度。同时采用Positive and Negative Syndrome Scale （PANSS）和Clinical Global Impression Scale （CGI）评估精神症状和疾病严重程度。精神分裂症组和健康对照组前扣带皮层GABA中位浓度分别为1.90 （Q1=1.55, Q3=2.09）和2.16 (Q1=1.87, Q3=2.59)；平均（sd） Glu浓度分别为6.07（2.48）和6.54 (1.99)；Gln浓度中位数分别为0.36 （Q1=0.00, Q3=0.74）和0.29 (Q1=0.00, Q3=0.59)；GABA浓度组间差异有统计学意义（Z=-2.95, p=0.003）；GABA/(NAA+NAAG)组间差异有统计学意义（Z=-2.72, p=0.012）；Glu、Gln组间差异无统计学意义。精神分裂症组年龄与前扣带GABA浓度呈负相关（R=-0.494, p=0.014），与GABA/ (NAA+NAAG)呈负相关（R=-0.473, p=0.020）。然而，在对照组中却没有这种相关性。经校正后，临床症状与代谢物浓度之间未发现显著相关性。精神分裂症患者脑正中前额叶皮层谷氨酸浓度异常，而前扣带皮层谷氨酸-GABA浓度下降，支持精神分裂症患者大脑谷氨酸-GABA异常的假设。在精神分裂症患者中，前扣带皮层中的GABA随着年龄的增长而加速下降。临床症状可能与前扣带皮层代谢物浓度有关。
The etiology and pathomechanism of schizophrenia are unknown. The traditional dopamine (DA) hypothesis is unable to fully explain its pathology and therapeutics. The glutamate (Glu) and γ-aminobutyric acid (GABA) hypotheses suggest Glu or GABA concentrations are abnormal in the brains of patients with schizophrenia. Magnetic resonance spectroscopy (MRS) show glutamate level increases in the ventromedial prefrontal cortex (vmPFC) including the anterior cingulated cortex (ACC) in those with schizophrenia. To investigate the function of the glutamate system (glutamate and γ-aminobutyric acid) in the etiology and pathomechanism of schizophrenia. 24 drug naïve patients with schizophrenia and 24 healthy volunteers were matched by gender, age, and educational level. The Siemens 3T MRI system was used to collect the magnetic resonance spectroscopy (MRS) data of the subjects. The regions of interest included the left dorsolateral prefrontal cortex (IDLPFC), ventromedial prefrontal cortex (vmPFC), and anterior cingulate cortex (ACC). LCModel software was used to analyze the concentrations of γ-aminobutyric acid (GABA), glutamate (Glu), glutamine (Gln), N-acetylaspartate (NAA), and N-acetylaspartylglutamate (NAAG) in the region of interest. Meanwhile, the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression Scale (CGI) were used to assess the mental symptoms and severity of the disease. The median GABA concentrations in the anterior cingulate cortex of the schizophrenia group and the healthy control group were 1.90 (Q1=1.55, Q3=2.09) and 2.16 (Q1=1.87, Q3=2.59) respectively; the mean (sd) Glu concentrations were 6.07 (2.48) and 6.54 (1.99); the median Gln concentrations were 0.36 (Q1=0.00, Q3=0.74) and 0.29 (Q1=0.00, Q3=0.59); the between-group difference of the GABA concentrations was statistically significant (Z=-2.95, p=0.003); the between-group difference of the GABA/(NAA+NAAG) was statistically significant (Z=-2.72, p=0.012); the between-group difference of Glu and Gln was not statistically significant. The age of the schizophrenia group was negatively correlated with the GABA concentration in the anterior cingulate (R=-0.494, p=0.014), and negatively correlated with GABA/ (NAA+NAAG) (R=-0.473, p=0.020). Yet there was no such correlation in the control group. After calibration, no significant correlation was found between the clinical symptoms and the concentrations of the metabolites. The concentration of glutamate in the vemtromedial prefrontal cortex of patients with schizophrenia was abnormal, whereas the concentration of GABA in the anterior cingulate cortex decreased, supporting the hypothesis of abnormal glutamate -GABA in the brains of those individuals with schizophrenia. In patients with schizophrenia, the GABA in the anterior cingulate cortex had an accelerated decline with age. The clinical symptoms may be correlated to the metabolite concentration of the anterior cingulate cortex.