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通过氢核磁共振对精神分裂症患者血清进行代谢组学和脂质组学分析,揭示了潜在的外周诊断生物标志物。

Metabolomics and lipidomics analyses by H nuclear magnetic resonance of schizophrenia patient serum reveal potential peripheral biomarkers for diagnosis.

作者信息

Tasic Ljubica, Pontes João G M, Carvalho Michelle S, Cruz Guilherme, Dal Mas Carolines, Sethi Sumit, Pedrini Mariana, Rizzo Lucas B, Zeni-Graiff Maiara, Asevedo Elson, Lacerda Acioly L T, Bressan Rodrigo A, Poppi Ronei Jesus, Brietzke Elisa, Hayashi Mirian A F

机构信息

Department of Organic Chemistry, Institute of Chemistry, Universidade Estadual de Campinas (UNICAMP), Campinas, Brazil.

Department of Organic Chemistry, Institute of Chemistry, Universidade Estadual de Campinas (UNICAMP), Campinas, Brazil.

出版信息

Schizophr Res. 2017 Jul;185:182-189. doi: 10.1016/j.schres.2016.12.024. Epub 2016 Dec 29.

Abstract

Using H NMR-based metabolomics in association to chemometrics analysis, we analyzed here the metabolic differences between schizophrenia patients (SCZ) compared to healthy controls (HCs). HCs and SCZ patients underwent clinical interview using the Structured Clinical Interview for DSM Disorders (SCID). SCZ patients were further assessed by Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale, Global Assessment of Functioning Scale (GAF), and Clinical Global Impressions Scale (CGI). Using the principal component analysis (PCA) and supervised partial least-squares discriminate analysis (PLS-DA) in obtained NMR data, a clear group separation between HCs and SCZ patients was achieved. Interestingly, all metabolite compounds identified as exclusively present in the SCZ group, except for the gamma-aminobutyric acid (GABA), were never previously associated with mental disorders. Although the initial perception of an absence of obvious biological link among the different key molecules exclusively observed in each group, and no identification of any specific pathway yet, the present work represents an important contribution for the identification of potential biomarkers to inform diagnosis, as it was possible to completely separate the affected SCZ patients from HCs, with no outliers or exceptions. In addition, the data presented here reinforced the role of the modulation of glycolysis pathway and the loss of GABA interneuron/hyperglutamate hypothesis in SCZ.

摘要

我们运用基于氢核磁共振波谱的代谢组学技术并结合化学计量学分析,在此分析了精神分裂症患者(SCZ)与健康对照者(HCs)之间的代谢差异。HCs和SCZ患者使用《精神疾病诊断与统计手册》障碍的结构化临床访谈(SCID)进行临床访谈。SCZ患者进一步通过阳性和阴性症状量表(PANSS)、卡尔加里抑郁量表、功能总体评定量表(GAF)和临床总体印象量表(CGI)进行评估。在获得的核磁共振数据中使用主成分分析(PCA)和监督偏最小二乘判别分析(PLS-DA),实现了HCs和SCZ患者之间明显的分组区分。有趣的是,除γ-氨基丁酸(GABA)外,所有被鉴定为仅存在于SCZ组中的代谢物化合物以前从未与精神障碍相关联。尽管最初认为在每组中专门观察到的不同关键分子之间不存在明显的生物学联系,并且尚未确定任何特定途径,但目前的工作对于识别潜在的生物标志物以指导诊断具有重要贡献,因为有可能将受影响的SCZ患者与HCs完全分开,没有异常值或例外情况。此外,此处呈现的数据强化了糖酵解途径调节以及GABA中间神经元丧失/高谷氨酸假说在SCZ中的作用。

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