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. 2017 Oct 25;29(5):277-286.
doi: 10.11919/j.issn.1002-0829.217004.

Abnormal Concentration of GABA and Glutamate in The Prefrontal Cortex in Schizophrenia.-An in Vivo 1H-MRS Study

Tianyi Chen  1   2 , Yingchan Wang  1 , Jianye Zhang  1 , Zuowei Wang  2 , Jiale Xu  3 , Yao Li  3 , Zhilei Yang  4 , Dengtang Liu  1
Affiliations

Abnormal Concentration of GABA and Glutamate in The Prefrontal Cortex in Schizophrenia.-An in Vivo 1H-MRS Study

Tianyi Chen et al. Shanghai Arch Psychiatry. .

Abstract
in English, Chinese

Background: 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.

Aims: To investigate the function of the glutamate system (glutamate and γ-aminobutyric acid) in the etiology and pathomechanism of schizophrenia.

Methods: 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.

Results: 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.

Conclusions: 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.

背景: 精神分裂症的病因及病理机制不明，传统的 多巴胺(Dopamine，DA) 假说不能完全解释其病理学 及治疗学。谷氨酸（glutamate，Glu）及γ- 氨基丁酸 （γ-aminobutyric acid，GABA）假说认为精神分裂症患 者脑内的Glu 或GABA 浓度异常。磁共振波谱(magnetic resonance spectroscopy，MRS) 技术发现精神分裂症 谷氨酸类物质水平在前额叶腹内侧（ventromedial prefrontal cortex，vmPFC）（包括前扣带回）(anterior cingulate cortex，ACC) 升高。.

目的: 探讨谷氨酸系统（谷氨酸及γ- 氨基丁酸）在精 神分裂症原因学及病理机制中的作用。.

方法: 24 例未服药精神分裂症患者及24 例性别、年 龄及教育程度相配的健康志愿者入组，应用西门子 MRI 3T 采集被试的磁共振波谱（magnetic resonance spectroscopy，MRS）数据，感兴趣区包括左侧前额叶 背外侧（left dorsolateral prefrontal cortex，IDLPFC）、 前额叶腹内侧（ventromedial prefrontal cortex， vmPFC）及前扣带回(anterior cingulate cortex，ACC)， 运用LCModel 软件分析了感兴趣区的γ- 氨基丁酸 （γ-aminobutyric acid，GABA）、谷氨酸（glutamate， Glu）、谷氨酰胺（glutamine，Gln）、氮乙酰天冬氨 酸（N-acetylaspartate，NAA）及氮乙酰天冬氨酸谷氨 酸（N-acetylaspartylglutamate，NAAG）等物质浓度。 同时应用阳性与阴性症状量表（positive and negative Syndrome scale，PANSS）及临床总体印象量表（Clinical Global Impression Scale，CGI）评估患者的精神症状和 疾病严重程度。.

结果: 精神分裂症组和健康对照组前扣带回的GABA 浓度分别为1.90（Q1=1.55，Q3=2.09）及2.16（Q1=1.87， Q3=2.59）、Glu 浓度分别为6.07（2.48）及6.54（1.99）、 Gln 浓度分别为0.36（Q1=0.00，Q3=0.74） 及0.29 （Q1=0.00，Q3=0.59），GABA 浓度的组间差异有统计 学意义（Z=-2.95，p =0.003），GABA/(NAA+NAAG) 的 组间差异有统计学意义（t=-2.72，p =0.012），而Glu 及Gln 的组间差异均无统计学意义。精神分裂症患者 组的年龄与前扣带回的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），但对照组无此相关性。经过FDR 方法校正 后，未发现临床症状与各代谢产物浓度无显著相关性。.

结论: 精神分裂症患者前额叶腹内侧的谷氨酸类物质 浓度异常，而前扣带回的GABA 浓度降低，支持精神 分裂症脑内谷氨酸-GABA 异常假说。精神分裂症患者 前扣带回的 GABA 随年龄增长加速减退。临床症状与 前扣带回的代谢物浓度可能相关。.

Keywords: glutamate; magnetic resonance spectroscopy; schizophrenia; γ-aminobutyric acid.

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Figures

Figure 1.
Figure 1.
Flowchart of the study
Figure 2.
Figure 2.
Size and location of the region of interest of the left dorsolateral prefrontal cortex (IDLPFC); the volume is 35mm X 25mm X 30mm
Figure 3.
Figure 3.
Size and location of the region of interest of the ventromedial prefrontal cortex (vmPFC); the volume is 20mm X 40mm X 30mm
Figure 4.
Figure 4.
Size and location of the region of interest of the anterior cingulate cortex (ACC); the volume is 40mm X 20mm X 20mm
See this image and copyright information in PMC

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