Variability and magnitude of brain glutamate levels in schizophrenia: a meta and mega-analysis.
Variability and magnitude of brain glutamate levels in schizophrenia: a meta and mega-analysis.
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DOI：
10.1038/s41380-023-01991-7
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发表时间：
2023-05
影响因子：
11
通讯作者：
Egerton, Alice
中科院分区：
文献类型：
--
作者：
Merritt, Kate;McCutcheon, Robert;Aleman, Andre;Ashley, Sarah;Beck, Katherine;Block, Wolfgang;Bloemen, Oswald J. N.;Borgan, Faith;Boules, Christiana;Bustillo, Juan R.;Capizzano, Aristides;Coughlin, Jennifer Q.;David, Anthony;de la Fuente-Sandoval, Camilo;Demjaha, Arsime;Dempster, Kara;Do, Kim;Du, Fei E.;Falkai, Peter;Galinska-Skok, Beata;Gallinat, Juergen;Gasparovic, Charles;Ginestet, Cedric E.;Goto, Naoki;Graff-Guerrero, Ariel;Ho, Beng-Choon;Howes, Oliver;Jauhar, Sameer;Jeon, Peter;Kato, Tadafumi;Kaufmann, Charles A.;Kegeles, Lawrence S.;Keshavan, Matcheri S.;Kim, Sang-Young;King, Bridget;Kunugi, Hiroshi;Lauriello, J.;Leon-Ortiz, Pablo;Liemburg, Edith;Mcilwain, Meghan;Modinos, Gemma;Mouchlianitis, Elias;Nakamura, Jun;Nenadic, Igor;Ongur, Dost;Ota, Miho;Palaniyappan, Lena E.;Pantelis, Christos;Patel, Tulsi F.;Plitman, Eric;Posporelis, Sotirios R.;Purdon, Scot;Reichenbach, Juergen R.;Renshaw, Perry C.;Reyes-Madrigal, Francisco;Russell, Bruce A.;Sawa, Akira;Schaefer, Martin;Shungu, Dikoma C.;Smesny, Stefan;Stanley, Jeffrey;Stone, James G.;Szulc, Agata;Taylor, Reggie;Thakkar, Katharine N.;Theberge, Jean J.;Tibbo, Philip;van Amelsvoort, Therese;Walecki, Jerzy;Williamson, Peter;Wood, Stephen;Xin, Lijing;Yamasue, Hidenori;McGuire, Philip K.;Egerton, Alice
谷氨酸能功能障碍与精神分裂症的病理学有关，但这在患者之间的程度可能不同。目前尚不清楚精神分裂症患者谷氨酸盐的个体间变异性是否大于一般人群。我们进行了荟萃分析，以评估（1）患者相对于对照组的谷氨酸测量值的变异性（对数变异系数比：CVR）;（2）使用Hedges g的标准化平均差异（SMD）;（3）个体水平谷氨酸数据的模态分布（Hartigan单峰浸渍检验）。检索MEDLINE和EMBASE数据库，从开始到2022年9月，寻找报告精神分裂症中谷氨酸、谷氨酰胺或Glx的质子磁共振波谱（1H-MRS）研究。纳入了123项研究，报告了8256例患者和7532例对照。与对照组相比，患者内侧额叶皮层中的多巴胺能代谢物表现出更大的变异性，（MFC，谷氨酸：CVR = 0.15，p < 0.001;谷氨酰胺：CVR = 0.15，p = 0.003; Glx：CVR = 0.11，p = 0.002），背外侧前额叶皮层（谷氨酰胺：CVR = 0.14，p = 0.05; Glx：CVR = 0.25，p < 0.001）和丘脑（谷氨酸：CVR = 0.16，p = 0.008; Glx：CVR = 0.19，p = 0.008）。在年轻、症状更多的患者中进行的研究与基底神经节的更大变异性相关（BG谷氨酸与年龄：z =-0.03，p = 0.003，症状：z = 0.007，p = 0.02）和颞叶（谷氨酸与年龄：z =-0.03，p = 0.02），而对年龄较大、症状较明显的患者进行的研究与MFC的变异性较大相关。（谷氨酸与年龄：z = 0.01，p = 0.02，谷氨酰胺与症状：z = 0.01，p = 0.02）。对于个体患者数据，大多数研究显示，多巴胺能代谢物呈单峰分布。平均差异的荟萃分析发现，与对照组相比，患者的MFC谷氨酸盐较低（g =-0.15，p = 0.03），丘脑谷氨酰胺较高（g = 0.53，p < 0.001），BG Glx较高（g = 0.28，p < 0.001）。相对于对照组，患者中男性比例与MFC谷氨酸盐（z =-0.02，p < 0.001）和额叶白色Glx（z =-0.03，p = 0.02）呈负相关。患者PANSS总评分与BG（z = 0.01，p = 0.01）和颞叶（z = 0.05，p = 0.008）中的谷氨酸SMD呈正相关。进一步研究精神分裂症中更大的谷氨酸能代谢物变异性及其临床后果的机制可能会为未来治疗策略的患者亚组识别提供信息。
Glutamatergic dysfunction is implicated in schizophrenia pathoaetiology, but this may vary in extent between patients. It is unclear whether inter-individual variability in glutamate is greater in schizophrenia than the general population. We conducted meta-analyses to assess (1) variability of glutamate measures in patients relative to controls (log coefficient of variation ratio: CVR); (2) standardised mean differences (SMD) using Hedges g; (3) modal distribution of individual-level glutamate data (Hartigan’s unimodality dip test). MEDLINE and EMBASE databases were searched from inception to September 2022 for proton magnetic resonance spectroscopy (1H-MRS) studies reporting glutamate, glutamine or Glx in schizophrenia. 123 studies reporting on 8256 patients and 7532 controls were included. Compared with controls, patients demonstrated greater variability in glutamatergic metabolites in the medial frontal cortex (MFC, glutamate: CVR = 0.15, p < 0.001; glutamine: CVR = 0.15, p = 0.003; Glx: CVR = 0.11, p = 0.002), dorsolateral prefrontal cortex (glutamine: CVR = 0.14, p = 0.05; Glx: CVR = 0.25, p < 0.001) and thalamus (glutamate: CVR = 0.16, p = 0.008; Glx: CVR = 0.19, p = 0.008). Studies in younger, more symptomatic patients were associated with greater variability in the basal ganglia (BG glutamate with age: z = −0.03, p = 0.003, symptoms: z = 0.007, p = 0.02) and temporal lobe (glutamate with age: z = −0.03, p = 0.02), while studies with older, more symptomatic patients associated with greater variability in MFC (glutamate with age: z = 0.01, p = 0.02, glutamine with symptoms: z = 0.01, p = 0.02). For individual patient data, most studies showed a unimodal distribution of glutamatergic metabolites. Meta-analysis of mean differences found lower MFC glutamate (g = −0.15, p = 0.03), higher thalamic glutamine (g = 0.53, p < 0.001) and higher BG Glx in patients relative to controls (g = 0.28, p < 0.001). Proportion of males was negatively associated with MFC glutamate (z = −0.02, p < 0.001) and frontal white matter Glx (z = −0.03, p = 0.02) in patients relative to controls. Patient PANSS total score was positively associated with glutamate SMD in BG (z = 0.01, p = 0.01) and temporal lobe (z = 0.05, p = 0.008). Further research into the mechanisms underlying greater glutamatergic metabolite variability in schizophrenia and their clinical consequences may inform the identification of patient subgroups for future treatment strategies.
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影响因子：
4.5
作者：
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作者：
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