Combined Application of NMR- and GC-MS-Based Metabonomics Yields a Superior Urinary Biomarker Panel for Bipolar Disorder

Abstract

Bipolar disorder (BD) is a debilitating mental disorder that cannot be diagnosed by objective laboratory-based modalities. Our previous studies have independently used nuclear magnetic resonance (NMR)-based and gas chromatography-mass spectrometry (GC-MS)-based metabonomic methods to characterize the urinary metabolic profiles of BD subjects and healthy controls (HC). However, the combined application of NMR spectroscopy and GC-MS may identify a more comprehensive metabolite panel than any single metabonomic platform alone. Therefore, here we applied a dual platform (NMR spectroscopy and GC-MS) that generated a panel of five metabolite biomarkers for BD-four GC-MS-derived metabolites and one NMR-derived metabolite. This composite biomarker panel could effectively discriminate BD subjects from HC, achieving an area under receiver operating characteristic curve (AUC) values of 0.974 in a training set and 0.964 in a test set. Moreover, the diagnostic performance of this panel was significantly superior to the previous single platform-derived metabolite panels. Thus, the urinary biomarker panel identified here shows promise as an effective diagnostic tool for BD. These findings also demonstrate the complementary nature of NMR spectroscopy and GC-MS for metabonomic analysis, suggesting that the combination of NMR spectroscopy and GC-MS can identify a more comprehensive metabolite panel than applying each platform in isolation.

Recent Advances in NMR-Based Metabolomics

“…One study combined NMR and GC–MS platforms to generate a panel of five urinary metabolite biomarkers for Bipolar Disorder (BD) (four GC–MS-derived and one NMR-derived). 86 This composite biomarker panel discriminated BD subjects from healthy controls with impressive area under the receiver operating characteristic curve (AUC) values of 0.974 in a training set and 0.964 in a test set, which is significantly superior to the previous single platform-derived metabolite panels. Urinary metabolic profiles of renal transplant patients with major injury factors at critical stages following transplantation were investigated by combining NMR and GC–MS.…”

Efficacy of ketamine in the rapid treatment of major depressive disorder: a meta-analysis of randomized, double-blind, placebo-controlled studies

“…However, there are still no objective laboratory tests to help clinicians in the diagnosis of MDD, although many studies have been done to develop these tests 4–6. Our group has conducted many studies for identifying potential biomarkers for MDD diagnosis using metabolomics,7–9 which is used to identify novel biomarkers for various disease states 10–12. Another dilemma about the prevention and treatment of MDD is that no existing antidepressants could treat MDD patients with 100% response rate.…”

Perturbational Profiling of Metabolites in Patient Fibroblasts Implicates α-Aminoadipate as a Potential Biomarker for Bipolar Disorder

“…Such studies have suggested the possibility of identifying biomarkers for schizophrenia [47,48,49,50,51,52], major depressive disorder [53,54] and posttraumatic stress disorder [55], and have also been used to study medication-induced metabolic changes [56,57]. In bipolar disorder, metabolomic studies have been undertaken in urine samples to identify potential biomarkers [58,59,60,61]. We report our findings from unbiased metabolic profiling of fibroblasts from patients with bipolar disorder and healthy controls, under normal growth conditions as well as under physiologic perturbations.…”