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.

Fig. 1

Flowchart of the study analyses in this work. MDD, major depressive disorder

Fig. 2

Heat plot of the differential metabolites in depression patients vs. healthy controls. drug-naive MDD drug-treated MDD healthy controls. MDD major depressive disorder

Fig. 3

ROC curves of inosine for a drug-naive MDD and b drug-treated MDD diagnosis. AUC area under the ROC curve, MDD major depressive disorder, ROC receiver-operating characteristic

Fig. 4

Perturbed metabolic pathways in drug-naive children and adolescents MDD and adults MDD subjects. Metabolites in red increased in the plasma, and metabolites in green decreased. ATP adenosine triphosphate, Fatty acids capric acid, cis-9-palmitoleic acid, dodecanoic acid, oleic acid, palmitic acid or stearic acid, MDD major depressive disorder, PUFAs eicosapentaenoic acid (EPA, ω-3) and arachidonic acid (AA, ω-6), SAM S-adenosylmethionine, TCA tricarboxylic acid cycle