Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India.
Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India.
Psychiatry Res Neuroimaging. 2020 Jun 30;300:111080. doi: 10.1016/j.pscychresns.2020.111080. Epub 2020 Apr 3.
Nearly a third to half of schizophrenia patients are non-responsive to first-line antipsychotics and are labelled treatment resistant schizophrenia (TRS). Neurochemical abnormalities in TRS may not be dopaminergic but possibly glutamate (Glu) related. Studies that have examined glutamatergic abnormalities using proton magnetic resonance spectroscopy (H-MRS) in TRS, have showed inconsistent results. Hence, we conducted a meta-analysis of H-MRS studies comparing levels of Glu-and its metabolites in the brains of TRS and non-treatment resistant schizophrenia (nTRS) patients. Four eligible studies were included in the analysis. Summary effect size for the group difference between TRS (n = 101, including Ultra-TRS) and nTRS (n = 61) in Glu-levels in the anterior cingulate cortex (ACC) as measured with Hedges's g was 0.21 (95% CI: -0.42 to 0.85; p = 0.5) suggesting absence of significant difference. However, on leave one out analysis, one iteration showed significant difference in Glu-levels between the groups (Hedges's g = 0.46; p = 0.02) with higher Glu-levels in TRS implying significant effect of a single study on the effect size. The higher ACC Glu-in TRS was not associated with symptom severity or antipsychotic administration, indicating a possible trait abnormality. The limited number of datasets comparing Glu-metabolites in other brain regions are narratively described. Our analysis is limited by the significant heterogeneity between studies. Further longitudinal, prospective studies are needed to confirm higher Glu-metabolite levels in ACC in TRS and explore this potential trait abnormality.
大约三分之一到一半的精神分裂症患者对一线抗精神病药物没有反应，被标记为治疗抵抗性精神分裂症（TRS）。TRS 中的神经化学异常可能不是多巴胺能的，而是谷氨酸（Glu）相关的。使用质子磁共振波谱（H-MRS）检查 TRS 中谷氨酸异常的研究结果不一致。因此，我们对比较 TRS（n=101，包括 Ultra-TRS）和非治疗抵抗性精神分裂症（nTRS）患者大脑中 Glu 及其代谢物水平的 H-MRS 研究进行了荟萃分析。有 4 项符合条件的研究纳入了分析。用 Hedges 的 g 测量的 ACC 中 Glu 水平的 TRS 组（n=101，包括 Ultra-TRS）和 nTRS 组（n=61）之间的组间差异的汇总效应大小为 0.21（95%CI：-0.42 至 0.85；p=0.5），表明无显著差异。然而，在逐一剔除分析中，有一次迭代显示两组之间的 Glu 水平存在显著差异（Hedges 的 g=0.46；p=0.02），TRS 中的 Glu 水平较高，这意味着单个研究对效应大小的影响显著。TRS 中较高的 ACC Glu 与症状严重程度或抗精神病药物治疗无关，表明可能存在特质异常。比较其他脑区 Glu 代谢物的数据集数量较少，故进行描述性叙述。我们的分析受到研究之间显著异质性的限制。需要进一步进行纵向、前瞻性研究以确认 TRS 中 ACC 中较高的 Glu 代谢物水平，并探讨这种潜在的特质异常。
