Glutamate, GABA and NAA in treatment-resistant schizophrenia: A systematic review of the effect of clozapine and group differences between clozapine-responders and non-responders

IF 2.6 3区心理学 Q2 BEHAVIORAL SCIENCES

Behavioural Brain Research Pub Date : 2024-11-19 DOI:10.1016/j.bbr.2024.115338

Milo Wolfgang Pilgaard Kristensen , Bahast Biuk , Jimmi Nielsen , Kirsten Borup Bojesen , Mette Ødegaard Nielsen

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引用次数: 0

Abstract

Treatment-resistance in patients with schizophrenia is a major obstacle for improving outcome in patients, especially in those not gaining from clozapine. Novel research implies that glutamatergic and GABAergic abnormalities may be present in treatment-resistant patients, and preclinical research suggests that clozapine affects the GABAergic system. Moreover, clozapine may have a neuroprotective role.

To investigate these issues, we conducted a systematic review to evaluate the relationship between clozapine and in vivo measures of gamma-aminobutyric acid (GABA), glutamate (glu), and N-acetylaspartate (NAA) brain levels in treatment- and ultra-treatment-resistant schizophrenia patients (TRS and UTRS).

Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we included three longitudinal and six cross sectional studies utilizing proton magnetic resonance spectroscopy (H-MRS) that explored brain metabolite levels in clozapine-treated patients.

Findings were limited by a small number of studies and definite conclusions cannot be drawn, but the present studies may imply that clozapine reduces glutamate levels in striatal but not cortical areas, whereas glutamatergic metabolites and GABA levels may be increased in ACC in the combined group of TRS and UTRS. Clozapine may also increase NAA in cortical areas. Importantly, this review highlights the need for further clinical studies investigating the effect of clozapine on brain levels of glutamate, GABA, and NAA as well as metabolite group differences in patients with UTRS compared with TRS.

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耐药性精神分裂症中的谷氨酸、GABA 和 NAA：氯氮平疗效的系统回顾以及氯氮平应答者和非应答者之间的群体差异。

精神分裂症患者的耐药性是改善患者预后的一大障碍，尤其是那些没有从氯氮平中获益的患者。新的研究表明，耐药患者可能存在谷氨酸能和 GABA 能异常，而临床前研究表明，氯氮平可影响 GABA 能系统。此外，氯氮平可能具有神经保护作用。为了研究这些问题，我们进行了一项系统性综述，评估氯氮平与治疗耐药和超治疗耐药精神分裂症患者（TRS 和 UTRS）体内γ-氨基丁酸（GABA）、谷氨酸（glu）和 N-乙酰天冬氨酸（NAA）脑水平测量值之间的关系。根据系统综述和荟萃分析首选报告项目（PRISMA）指南，我们纳入了三项纵向研究和六项横断面研究，这些研究利用质子磁共振波谱（H-MRS）检测了氯氮平治疗患者的脑代谢物水平。研究结果因研究数量较少而受到限制，无法得出明确结论，但目前的研究可能意味着氯氮平降低了纹状体而非皮质区域的谷氨酸水平，而在 TRS 和 UTRS 合并组中，谷氨酸代谢物和 GABA 水平可能在 ACC 中升高。氯氮平也可能增加皮质区域的 NAA。重要的是，本综述强调有必要进一步开展临床研究，探讨氯氮平对谷氨酸、GABA 和 NAA 的影响，以及与 TRS 相比，UTRS 患者的代谢物组别差异。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Behavioural Brain Research 医学-行为科学

CiteScore

5.60

自引率

0.00%

发文量

383

审稿时长

61 days

期刊介绍： Behavioural Brain Research is an international, interdisciplinary journal dedicated to the publication of articles in the field of behavioural neuroscience, broadly defined. Contributions from the entire range of disciplines that comprise the neurosciences, behavioural sciences or cognitive sciences are appropriate, as long as the goal is to delineate the neural mechanisms underlying behaviour. Thus, studies may range from neurophysiological, neuroanatomical, neurochemical or neuropharmacological analysis of brain-behaviour relations, including the use of molecular genetic or behavioural genetic approaches, to studies that involve the use of brain imaging techniques, to neuroethological studies. Reports of original research, of major methodological advances, or of novel conceptual approaches are all encouraged. The journal will also consider critical reviews on selected topics.