Polyunsaturated fatty acids metabolism, purine metabolism and inosine as potential independent diagnostic biomarkers for major depressive disorder in children and adolescents

Abstract

Major depressive disorder (MDD) in children and adolescents is a recurrent and disabling condition globally but its pathophysiology remains poorly elucidated and there are limited effective treatments available. We performed metabolic profiling of plasma samples based on ultra-high-performance liquid chromatography equipped with quadrupole time-offlight mass spectrometry to explore the potential biomarkers of depression in children and adolescents with MDD. We identified several perturbed pathways, including fatty acid metabolism-particularly the polyunsaturated fatty acids metabolism, and purine metabolism-that were associated with MDD in these young patients. In addition, inosine was shown as a potential independent diagnostic biomarker for MDD, achieving an area under the ROC curve of 0.999 in discriminating drug-naive MDD patients and 0.866 in discriminating drug-treated MDD from healthy controls. Moreover, we found evidence for differences in the pathophysiology of MDD in children and adolescents to that of adult MDD, specifically with tryptophan metabolism. Through metabolomic analysis, we have identified links between a framework of metabolic perturbations and the pathophysiology and diagnostic biomarker of child and adolescent MDD.

Purinergic Signaling and Related Biomarkers in Depression

“…Data demonstrated lower levels of both inosine and guanosine, as well as higher levels of xanthine. A recent study carried out a metabolic profiling of plasma samples to explore the potential biomarkers of major depressive disorder in children and adolescents [103]. Authors identified several abnormal pathways, including purine metabolism, and highlighted that inosine might be a possible independent diagnostic biomarker of depression, achieving an area under the receiver operating characteristic curve of 0.999 and 0.866 in the identification of drug-naïve and drug-treated subjects with major depressive disorder, respectively.…”

High rumen degradable starch decreased goat milk fat via trans-10, cis-12 conjugated linoleic acid-mediated downregulation of lipogenesis genes, particularly, INSIG1

“…Approximately 100 μL of plasma was preprocessed for metabolomic analyses. The derivatives of the sample were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS), and the acquired data were processed as described in a previous study [28]. Metabolic profiling of mammary venous plasma was performed using an ultrahigh-performance liquid chromatography (UHPLC) instrument (1290 Infinity LC, Agilent Technologies) coupled to triple time-of-flight mass spectrometer (AB Sciex TripleTOF 5600) at Shanghai Applied Protein Technology Co., Ltd. Metabolic pathway analysis of the identified metabolites in MRDS vs. LRDS, HRDS vs. LRDS and HRDS vs. MRDS were determined using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database (http://www.genome.jp/kegg/).…”

Gut Microbiota Is the Key to the Antidepressant Effect of Chaihu-Shu-Gan-San

“…It is also an important pyridine bacterial secondary metabolite [20]. In addition, H8 is an intermediate in the metabolism of adenosine, which plays a role in energy transfer as ATP and serves as a strong pro-inflammatory danger signal targeting specifically gram-positive bacteria [21]; meanwhile, H8 is a potential independent diagnostic biomarker for major depressive disorder (MDD) in children and adolescents [22]. Although we found the above results interesting, further study to explore the direct relationship of these two metabolites to CSGS effects related to gut microbiota is necessary.…”