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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.

SUBMITTER: Zhou X

PROVIDER: S-EPMC6756100 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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

Zhou Xinyu X Liu Lanxiang L Lan Xinghui X Cohen David D Zhang Yuqing Y Ravindran Arun V AV Yuan Shuai S Zheng Peng P Coghill David D Yang Lining L Hetrick Sarah E SE Jiang Xiaofeng X Benoliel Jean-Jacques JJ Cipriani Andrea A Xie Peng P

Molecular psychiatry 20180420 10

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 pathwa ...[more]

PMID: 29679072

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Project description:This study aims to examine the association of whole blood n-3 and n-6 polyunsaturated fatty acids (PUFA) with insulin resistance (IR) in children. Whole blood fatty acids were measured in 705 children aged 2-9 years of the European IDEFICS/I.Family cohort using gas chromatography in units of weight percentage of all detected fatty acids (%wt/wt). IR was determined by the Homeostasis Model Assessment for IR (HOMA). Mixed effect models were used to assess the associations between selected baseline PUFA and HOMA z-scores at baseline and after 2- and 6-year follow-ups using models with basic and additional confounder adjustment as well as stratified by sex and weight status. In the basic model, α-linolenic (β = 1.46 SD/%wt/wt, p = 0.006) and eicosapentaenoic acid (β = 1.17 SD/%wt/wt, p = 0.001) were positively associated with baseline HOMA z-score. In the stratified analyses, α-linolenic acid was positively associated with HOMA z-score in girls only (β = 1.98 SD/%wt/wt, p = 0.006) and arachidonic acid was inversely associated with baseline HOMA in thin/normal-weight children (β = - 0.13 SD/%wt/wt, p = 0.0063). In the fully adjusted model, no statistically significant associations were seen.Conclusions: Our overall results do not indicate a protective role of higher blood n-3 PUFA or an adverse role of higher blood arachidonic acid proportion on the risk of IR. What is Known: •Intervention studies reported a beneficial effect of n-3 PUFA supplementation on insulin resistance compared with placebo while observational studies in cildren are inconclusive. •Studies have shown a positive association of n-6 arachidonic acid and insulin resistance indicating an adverse role of arachidonic acid. What is New: •Cross-sectional and longitudinal analyses based on circulating blood fatty acid concentrations in a large cohort of European children and adolescents. •Overall results do not support a protective role of n-3 PUFA or an adverse role of arachidonic acid in insulin resistance.

Dataset Information

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

Publications

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

Similar Datasets

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