Glutamate and Gamma-Aminobutyric Acid Abnormalities in Antipsychotic-Naïve Patients With Schizophrenia: Evidence From Empirical and Meta-analytic Studies Using Magnetic Resonance Spectroscopy.
Glutamate and Gamma-Aminobutyric Acid Abnormalities in Antipsychotic-Naïve Patients With Schizophrenia: Evidence From Empirical and Meta-analytic Studies Using Magnetic Resonance Spectroscopy.
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DOI：
10.1016/j.biopsych.2020.11.005
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发表时间：
2021-02-01
影响因子：
10.6
通讯作者：
Reid MA
中科院分区：
文献类型：
--
作者：
Reid MA
谷氨酸和GABA（γ-氨基丁酸），主要的兴奋性和抑制性神经递质，分别在认知过程中发挥关键作用。来自临床前、尸检和人类神经影像学研究的证据表明，谷氨酸和GABA参与了精神病和精神分裂症的病理生理学。用于治疗精神分裂症的抗精神病药物主要是多巴胺拮抗剂，通常治疗阳性症状，对认知缺陷影响不大，这可能特别使人衰弱并导致功能结局不良。因此，谷氨酸能和GABA能系统是开发新药物的有希望的靶点。磁共振波谱（MRS）可以测量体内谷氨酸和GABA，因此它是研究人员寻求更好地了解精神分裂症病理生理学的有用工具。在最新一期的《生物精神病学》中，Bojesen等人的原始研究。(1)以及Kaminski et al. (2)强调了MRS对于进一步了解精神分裂症谱系障碍中谷氨酸和GABA功能障碍以及认知缺陷的本质的价值。Bojesen等人。(1)研究了一个大的抗精神病药物初治的精神分裂症和其他精神障碍患者群体中认知功能和神经代谢物之间的关系。他们使用3 T MRS测量前扣带皮层（ACC）和左丘脑中的GABA代谢物，然后研究这些代谢物与注意力、工作记忆和病前智力指标之间的关系。他们发现精神分裂症和精神病患者ACC中的GABA较低，精神分裂症患者亚组中丘脑中的谷氨酸较高，并且ACC谷氨酸加谷氨酰胺（Glx）与患者和对照组的工作记忆呈正相关。
Glutamate and GABA (gamma-aminobutyric acid), the major excitatory and inhibitory neurotransmitters, respectively, play key roles in cognitive processes. Converging evidence from preclinical, postmortem, and human neuroimaging studies indicates that glutamate and GABA are involved in the pathophysiology of psychosis and schizophrenia. Antipsychotic medications used to treat schizophrenia are primarily dopamine antagonists and generally treat the positive symptoms with little effect on cognitive deficits, which can be especially debilitating and lead to poor functional outcomes. Consequently, the glutamatergic and GABAergic systems are promising targets for the development of novel medications. Magnetic resonance spectroscopy (MRS) can measure glutamate and GABA in vivo, so it is a useful tool for researchers seeking to better understand the pathophysiology of schizophrenia. In the current issue of Biological Psychiatry, original research by Bojesen et al.(1) and a meta-analysis by Kaminski et al.(2) highlight the value of MRS to further our understanding of the nature of glutamate and GABA dysfunction and cognitive deficits in schizophrenia spectrum disorders.Bojesen et al.(1) investigated the relationship between cognitive function and neurometabolites in a large group of antipsychotic-naïve patients with schizophrenia and other psychotic disorders. They used 3T MRS to measure glutamatergic metabolites in the anterior cingulate cortex (ACC) and the left thalamus as well as GABA in the ACC. They then examined associations between these metabolites and measures of attention, working memory, and premorbid intelligence. They found lower GABA in the ACC of patients with schizophrenia and psychosis, higher glutamate in the thalamus in the subgroup of patients with schizophrenia, and a positive relationship between ACC glutamate plus glutamine (Glx) and working memory in the pooled group of patients and control subjects.
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