Liu Mei-Ling, Zheng Peng, Liu Zhao, Xu Yi, Mu Jun, Guo Jing, Huang Ting, Meng Hua-Qing, Xie Peng
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, P. R. China 400016.
Mol Biosyst. 2014 Jul 29;10(9):2398-406. doi: 10.1039/c4mb00157e.
Schizophrenia is a debilitating mental disorder. Currently, the lack of disease biomarkers to support objective laboratory tests constitutes a bottleneck in the clinical diagnosis of schizophrenia. Here, a gas chromatography-mass spectrometry (GC-MS) based metabolomic approach was applied to characterize the metabolic profile of schizophrenia subjects (n = 69) and healthy controls (n = 85) in peripheral blood mononuclear cells (PBMCs) to identify and validate biomarkers for schizophrenia. Multivariate statistical analysis was used to visualize group discrimination and to identify differentially expressed metabolites in schizophrenia subjects relative to healthy controls. The multivariate statistical analysis demonstrated that the schizophrenia group was significantly distinguishable from the control group. In total, 18 metabolites responsible for the discrimination between the two groups were identified. These differential metabolites were mainly involved in energy metabolism, oxidative stress and neurotransmitter metabolism. A simplified panel of PBMC metabolites consisting of pyroglutamic acid, sorbitol and tocopherol-α was identified as an effective diagnostic tool, yielding an area under the receiver operating characteristic curve (AUC) of 0.82 in the training samples (45 schizophrenia subjects and 50 healthy controls) and 0.71 in the test samples (24 schizophrenic patients and 35 healthy controls). Taken together, these findings help to develop diagnostic tools for schizophrenia.
精神分裂症是一种使人衰弱的精神障碍。目前，缺乏支持客观实验室检测的疾病生物标志物构成了精神分裂症临床诊断的瓶颈。在此，基于气相色谱-质谱联用（GC-MS）的代谢组学方法被用于表征精神分裂症患者（n = 69）和健康对照者（n = 85）外周血单核细胞（PBMCs）的代谢谱，以识别和验证精神分裂症的生物标志物。多变量统计分析用于直观显示组间差异，并识别精神分裂症患者相对于健康对照者中差异表达的代谢物。多变量统计分析表明，精神分裂症组与对照组有显著差异。总共鉴定出18种导致两组间差异的代谢物。这些差异代谢物主要参与能量代谢、氧化应激和神经递质代谢。由焦谷氨酸、山梨醇和α-生育酚组成的简化PBMC代谢物组被确定为一种有效的诊断工具，在训练样本（45例精神分裂症患者和50例健康对照者）中的受试者工作特征曲线下面积（AUC）为0.82，在测试样本（24例精神分裂症患者和35例健康对照者）中为0.71。综上所述，这些发现有助于开发精神分裂症的诊断工具。
