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.
Background
Heart failure (HF) is associated with ventricular dyssynchrony and energetic inefficiency, which can be alleviated by cardiac resynchronization therapy (CRT). The aim of this study was to determine the metabolomic signature in HF and its prognostic value for the response to CRT.
Methods
This prospective study consisted of 24 patients undergoing CRT for advanced HF and 10 control patients who underwent catheter ablation for supraventricular arrhythmia but not CRT. Blood samples were collected before and 3 months after CRT. Metabolomic profiling of plasma samples was performed using gas chromatography–mass spectrometry and nuclear magnetic resonance.
Results
The plasma metabolomic profile was altered in the HF patients, with a distinct panel of metabolites, including Krebs cycle and lipid, amino acid, and nucleotide metabolism. CRT improved the metabolic profile. The succinate/glutamate ratio, an index of Krebs cycle activity, improved from 0.58±0.13 to 2.84±0.60 (P<.05). The glucose/palmitate ratio, an indicator of the balance between glycolytic and fatty acid metabolism, increased from 0.96±0.05 to 1.54±0.09 (P<.01). Compared with the nonresponders to CRT, the responders had a distinct baseline plasma metabolomic profile, including higher isoleucine, phenylalanine, leucine, glucose, and valine levels and lower glutamate levels at baseline (P<.05).
Conclusion
CRT improves plasma metabolomic profile of HF patients indicating harmonization of myocardial energy substrate metabolism. CRT responders may have a favorable metabolic profile as a potential biomarker for predicting CRT outcome.
2DS is a feasible approach to assess regional ventricular systolic function in the fetal hearts and it can be used to examine cardiac systolic function in GDM fetuses with good glycemic control.
BackgroundSchizophrenia is a widespread and debilitating mental disorder. However, the underlying molecular mechanism of schizophrenia remains largely unknown and no objective laboratory tests are available to diagnose this disorder. The aim of the present study was to characterize the alternations of glucose metabolites and identify potential diagnostic biomarkers for schizophrenia.MethodsGas chromatography/mass spectrometry based targeted metabolomic method was used to quantify the levels of 13 glucose metabolites in peripheral blood mononuclear cells (PBMCs) derived from healthy controls, schizophrenia and major depression subjects (n = 55 for each group).ResultsThe majority (84.6%) of glucose metabolites were significantly disturbed in schizophrenia subjects, while only two (15.4%) glucose metabolites were differently expressed in depression subjects relative to healthy controls in both training set (n = 35/group) and test set (n = 20/group). Antipsychotics had only a subtle effect on glucose metabolism pathway. Moreover, ribose 5-phosphate in PBMCs showed a high diagnostic performance for first-episode drug-naïve schizophrenia subjects.ConclusionThese findings suggested disturbance of glucose metabolism may be implicated in onset of schizophrenia and could aid in development of diagnostic tool for this disorder.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0540-y) contains supplementary material, which is available to authorized users.
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