GABA and glutamate in schizophrenia: a 7 T ¹H-MRS study.
GABA and glutamate in schizophrenia: a 7 T ¹H-MRS study.
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精神分裂症中的GABA和谷氨酸：一项7 t 2 h-MRS研究。
DOI：
10.1016/j.nicl.2014.10.005
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Hulshoff Pol HE
中科院分区：
文献类型：
--
作者：
Marsman A;Mandl RC;Klomp DW;Bohlken MM;Boer VO;Andreychenko A;Cahn W;Kahn RS;Luijten PR;Hulshoff Pol HE
精神分裂症的特点是脑容量减少，这可能是一个持续的病理生理过程。这种脑容量的减少可能是由于神经体积的减少而不是神经元的损失，这表明突触可塑性和皮层微回路异常。可能的机制是nmda型谷氨酸受体功能减退，抑制gaba能中间神经元的兴奋，导致谷氨酸能锥体神经元的去抑制。锥体细胞的去抑制可引起谷氨酸的过度刺激，进而通过兴奋毒性引起神经元损伤或死亡。在7 t的超高磁场强度下，采用质子磁共振波谱法测量了17例精神分裂症患者和23例健康对照的前额叶和顶枕叶皮层GABA/肌酸比值以及谷氨酸、NAA、肌酸和胆碱浓度。结果表明，精神分裂症患者前额叶皮层GABA/Cr比值明显低于健康对照。GABA/Cr比值与患者的认知功能呈负相关。顶枕皮质GABA/Cr比值在患者和对照组之间无显著变化，前额叶和顶枕皮质谷氨酸、NAA、肌酸和胆碱水平在患者和对照组之间无差异。我们的研究结果支持了一种机制，即精神分裂症患者，特别是高功能患者，其内侧前额叶皮层GABA水平与谷氨酸水平不同。GABA通过改变前额叶皮层抑制性神经传递的（代偿）作用可能在精神分裂症（高功能）患者中持续存在。在7 t时使用1H-MRS测量精神分裂症患者和健康对照的GABA和谷氨酸水平，患者的前额叶GABA水平明显降低，谷氨酸水平未见变化。患者前额叶GABA水平与总智商呈负相关。这表明GABA与前额皮质中的谷氨酸有不同的作用机制。GABA可能在（高功能）患者的前额皮质中起代偿作用。
Schizophrenia is characterized by loss of brain volume, which may represent an ongoing pathophysiological process. This loss of brain volume may be explained by reduced neuropil rather than neuronal loss, suggesting abnormal synaptic plasticity and cortical microcircuitry. A possible mechanism is hypofunction of the NMDA-type of glutamate receptor, which reduces the excitation of inhibitory GABAergic interneurons, resulting in a disinhibition of glutamatergic pyramidal neurons. Disinhibition of pyramidal cells may result in excessive stimulation by glutamate, which in turn could cause neuronal damage or death through excitotoxicity. In this study, GABA/creatine ratios, and glutamate, NAA, creatine and choline concentrations in the prefrontal and parieto-occipital cortices were measured in 17 patients with schizophrenia and 23 healthy controls using proton magnetic resonance spectroscopy at an ultra-high magnetic field strength of 7 T. Significantly lower GABA/Cr ratios were found in patients with schizophrenia in the prefrontal cortex as compared to healthy controls, with GABA/Cr ratios inversely correlated with cognitive functioning in the patients. No significant change in the GABA/Cr ratio was found between patients and controls in the parieto-occipital cortex, nor were levels of glutamate, NAA, creatine, and choline differed in patients and controls in the prefrontal and parieto-occipital cortices. Our findings support a mechanism involving altered GABA levels distinguished from glutamate levels in the medial prefrontal cortex in schizophrenia, particularly in high functioning patients. A (compensatory) role for GABA through altered inhibitory neurotransmission in the prefrontal cortex may be ongoing in (higher functioning) patients with schizophrenia. GABA and glutamate were measured in schizophrenia patients and healthy controls using 1H-MRS at 7 T. Patients showed significantly lower prefrontal GABA levels, and no changes were found for glutamate. Prefrontal GABA levels were inversely correlated with total IQ in patients. This suggests a mechanism involving GABA distinguished from glutamate in the prefrontal cortex. GABA may have a compensatory role in the prefrontal cortex in (higher functioning) patients.
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影响因子：
2.9
作者：
Boer, V. O.;van Lier, A. L. H. M. W.;Klomp, D. W. J.
通讯作者：
Klomp, D. W. J.
影响因子：
3.3
作者：
GRUETTER, R
通讯作者：
GRUETTER, R
影响因子：
4.2
作者：
Gasparovic, Charles;Yeo, Ronald;Mayer, Andrew R.
通讯作者：
Mayer, Andrew R.
影响因子：
10.6
作者：
Andreasen, Nancy C.;Pressler, Marcus;Nopoulos, Peg;Miller, Del;Ho, Beng-Choon
通讯作者：
Ho, Beng-Choon
影响因子：
--
作者：
Kegeles, Lawrence S.;Mao, Xiangling;Shungu, Dikoma C.
通讯作者：
Shungu, Dikoma C.