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Dysregulations of amino acid metabolism and lipid metabolism in urine of children and adolescents with major depressive disorder: a case-control study

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Abstract

Rationale

The mechanisms underlying major depressive disorder (MDD) in children and adolescents are unclear. Metabolomics has been utilized to capture metabolic signatures of various psychiatric disorders; however, urinary metabolic profile of MDD in children and adolescents has not been studied.

Objectives

We analyzed urinary metabolites in children and adolescents with MDD to identify potential biomarkers and metabolic signatures.

Methods

Here, liquid chromatography-mass spectrometry was used to profile metabolites in urine samples from 192 subjects, comprising 80 individuals with antidepressant-naïve MDD (AN-MDD), 37 with antidepressant-treated MDD (AT-MDD) and 75 healthy controls (HC). We performed orthogonal partial least squares discriminant analysis to identify differential metabolites and employed logistic regression and receiver operating characteristic analysis to establish a diagnostic panel.

Results

In total, 143 and 71 differential metabolites were identified in AN-MDD and AT-MDD, respectively. These were primarily linked to lipid metabolism, molecular transport, and small molecule biochemistry. AN-MDD additionally exhibited dysregulated amino acid metabolism. Compared to HC, a diagnostic panel of seven metabolites displayed area under the receiver operating characteristic curves of 0.792 for AN-MDD, 0.828 for AT-MDD, and 0.799 for all MDD. Furthermore, the urinary metabolic profiles of children and adolescents with MDD significantly differed from those of adult MDD.

Conclusions

Our research suggests dysregulated amino acid metabolism and lipid metabolism in the urine of children and adolescents with MDD, similar to results in plasma metabolomics studies. This contributes to the comprehension of mechanisms underlying children and adolescents with MDD.

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Acknowledgements

We gratefully acknowledge the staff from the Department of Psychiatry and the Health Management Center, the First Affiliated Hospital of Chongqing Medical University (Chongqing, China), for their contributions to subject recruitment and sample collection.

Funding

This research was financially supported by the Major Program of Brain Science and Brain-Like Intelligence Technology (Grant No. 2022ZD0212900 to XZ), the National Natural Science Foundation of China (Grant No. 82271565 to XZ), the institutional funds from the Chongqing Science and Technology Commission (Grant No. cstc2020jcyj-jqX0024 to XZ), Shanghai Municipal Science and Technology Major Project (Grant No. 2019SHZDZX02 to ZZ), Shanghai Key Laboratory of Aging Studies (Grant No. 19DZ2260400 to ZZ), the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation (Grant No. GZB20230916 to TT), and the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation (Grant No. 2023TQ0398 to TT).

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  1. Yuanliang Jiang, Yuping Cai and Teng Teng contributed equally to this work.

Authors and Affiliations

  1. Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China

    Yuanliang Jiang, Teng Teng, Bangmin Yin, Xuemei Li, Xueer Liu, Jie Wang, Hongyan Wu & Xinyu Zhou

  2. Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China

    Yuping Cai & Zheng-Jiang Zhu

  3. Health Management Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China

    Xiaolin Wang

  4. Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China

    Ying Yu & Yuqian He

  5. Shanghai Key Laboratory of Aging Studies, Shanghai, China

    Zheng-Jiang Zhu

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  1. Yuanliang Jiang
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  2. Yuping Cai
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Contributions

XZ, ZZ, and YJ designed the research. YJ, TT, XW, XML, YY, XEL, JW, HW, and YH recruited subjects. ZZ, YJ, YC, TT, and BY analyzed the data. XZ, YJ, YC, and TT drafted the manuscript. XZ, and ZZ supervised the project. All authors contributed to the article and approved the submitted version.

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Correspondence to Zheng-Jiang Zhu or Xinyu Zhou.

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Xinyu Zhou and Zheng-Jiang Zhu jointly supervised this work.

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Jiang, Y., Cai, Y., Teng, T. et al. Dysregulations of amino acid metabolism and lipid metabolism in urine of children and adolescents with major depressive disorder: a case-control study. Psychopharmacology (2024). https://doi.org/10.1007/s00213-024-06590-0

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