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Mol Psychiatry. 2019 Oct;24(10):1478-1488. doi: 10.1038/s41380-018-0047-z. Epub 2018 Apr 20.

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

Author information

1
Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
2
Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
3
Department of Psychiatry, Children's Hospital of Chongqing Medical University, Chongqing, China.
4
Department of Child and Adolescent Psychiatry, Hôpital Pitié-Salpétrière, Institut des Systèmes Intelligents et Robotiques, Université Pierre et Marie Curie, Paris, France.
5
Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
6
Departments of Paediatrics and Psychiatry, University of Melbourne, Melbourne, Australia.
7
Centre for Youth Mental Health, University of Melbourne, Melbourne, Australia.
8
Department of Psychological Medicine, University of Auckland, Auckland, New Zealand.
9
UMRS 975, Pain Team, Site Pitie´-Salpeˆtrie're, Universite´ Pierre et Marie Curie-Paris 6, Paris, 75013, France.
10
Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK. andrea.cipriani@psych.ox.ac.uk.
11
Oxford Health NHS Foundation Trust, Oxford, UK. andrea.cipriani@psych.ox.ac.uk.
12
Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. xiepeng973@126.com.
13
Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China. xiepeng973@126.com.

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.

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