Glutamatergic Neurometabolite Levels in Patients With Ultra-Treatment-Resistant Schizophrenia: A Cross-Sectional 3T Proton Magnetic Resonance Spectroscopy Study
Glutamatergic Neurometabolite Levels in Patients With Ultra-Treatment-Resistant Schizophrenia: A Cross-Sectional 3T Proton Magnetic Resonance Spectroscopy Study
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DOI：
10.1016/j.biopsych.2018.09.009
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发表时间：
2019-04-01
影响因子：
10.6
通讯作者：
Graff-Guerrero, Ariel
中科院分区：
文献类型：
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作者：
Iwata, Yusuke;Nakajima, Shinichiro;Graff-Guerrero, Ariel
背景资料：就抗精神病药物治疗反应而言，精神分裂症患者可分为3组：1）对非氯氮平（非CLZ）抗精神病药物和CLZ均耐药（超耐药精神分裂症[URS]），2）对非CLZ抗精神病药物耐药但对CLZ有反应的精神分裂症[非URS]），3）对一线抗精神病药物有反应（非耐药精神分裂症）。本研究的目的是比较这三个患者组和健康对照组之间的谷氨酸能神经代谢物水平使用质子磁共振spectroscopic.Methods：谷氨酸和谷氨酸+谷氨酰胺水平进行了评估，在尾状核，背侧前扣带皮层（dACC），背外侧前额叶皮质使用3 T质子磁共振波谱（点分辨光谱，回波时间= 35毫秒）。结果：共纳入100例受试者，其中URS患者26例，非URS患者27例，非难治性精神分裂症患者21例，健康对照组26例。ACC谷氨酸+谷氨酰胺水平检测到组间差异（F3，96 = 2.93，p = 0.038）; URS患者的dACC谷氨酸+谷氨酰胺水平高于健康对照受试者（p = 0.038）。尾状核或背外侧前额叶cortex.Conclusions：与以往的研究表明，较高的ACC谷氨酸水平的患者治疗难治性精神分裂症，这项研究表明，较高水平的ACC谷氨酸代谢产物可能是共同的生物学特性的抗精神病药物，包括CLZ的治疗抗性。
Background: In terms of antipsychotic treatment response, patients with schizophrenia can be classified into three groups: 1) treatment resistant to both non-clozapine (non-CLZ) antipsychotics and CLZ (ultra-treatment-resistant schizophrenia [URS]), 2) treatment resistant to non-CLZ antipsychotics but CLZ-responsive schizophrenia [non-URS]), and 3) responsive to first-line antipsychotics (non-treatment-resistant schizophrenia). This study aimed to compare glutamatergic neurometabolite levels among these three patient groups and healthy control subjects using proton magnetic resonance spectroscopy.Methods: Glutamate and glutamate+glutamine levels were assessed in the caudate, the dorsal anterior cingulate cortex (dACC), and the dorsolateral prefrontal cortex using 3T proton magnetic resonance spectroscopy (point-resolved spectroscopy, echo time = 35 ms). Glutamatergic neurometabolite levels were compared between the groups.Results: A total of 100 participants were included, consisting of 26 patients with URS, 27 patients with non-URS, 21 patients with non-treatment-resistant schizophrenia, and 26 healthy control subjects. Group differences were detected in ACC glutamate+glutamine levels (F3,96 = 2.93, p = .038); patients with URS showed higher dACC glutamate+glutamine levels than healthy control subjects (p = .038). There were no group differences in the caudate or dorsolateral prefrontal cortex.Conclusions: Taken together with previous studies that demonstrated higher ACC glutamate levels in patients with treatment-resistant schizophrenia, this study suggests that higher levels of ACC glutamatergic metabolites may be among the shared biological characteristics of treatment resistance to antipsychotics, including CLZ.