Plasma Lipidomic Features of Adolescent Major Depressive Disorder and Lipid Changes After Fluoxetine Treatment
- 1Department of Psychiatry, Key Laboratory of Major Brain Disease and Aging Research (Ministry of Education), The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Abstract
Background
Major depressive disorder (MDD) in adolescents is a major public health concern, yet objective biological markers and treatment-related metabolic changes remain insufficiently understood. This study aimed to characterize plasma lipidomic alterations in adolescent MDD and explore lipid changes associated with fluoxetine treatment.Methods
This study enrolled 75 adolescents with MDD and 75 matched healthy controls (HCs). Among the adolescents with MDD, 44 had paired baseline and week-8 plasma samples available and were included in the longitudinal analysis. Plasma lipidomic profiles were analyzed using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS).Results
A total of 865 lipid species were detected. Compared with HCs, adolescents with MDD showed distinct plasma lipidomic profiles, with 82 differentially abundant lipid species identified, primarily involving triglycerides, lysophospholipids, free fatty acids, membrane phospholipids, and sphingolipids. Among the machine-learning models, logistic regression showed the highest discriminative performance, with a pooled out-of-fold AUC of 0.85 (95% CI, 0.79-0.91). Longitudinal analysis identified 21 lipid species meeting the differential criteria following fluoxetine treatment, mainly involving triglycerides and bile acid-related metabolites. Integrative pathway and target analyses suggested that fluoxetine-associated lipid changes may involve neurotransmitter signaling, inflammatory lipid metabolism, PI3K-Akt signaling, and nuclear receptor-related pathways.Conclusion
This study characterizes alterations in plasma lipid metabolism in adolescent MDD and the lipidomic changes following fluoxetine treatment, providing new lipidomic evidence for candidate lipid signatures and potential treatment-associated biological pathways.Trial registration
ClinicalTrials.gov, NCT05814640. Registered 20 February 2023, https://clinicaltrials.gov/study/NCT05814640.
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BibTeX
@article{liu2026plasma,
title = {{Plasma Lipidomic Features of Adolescent Major Depressive Disorder and Lipid Changes After Fluoxetine Treatment}},
author = {Chenxi Liu and Yao Li and Hanchen Hou and Jiamei Guo and Bingjie Qin and Xiaoxia Xu and Yuqian He and Tingting Lei and Fei Chen and Lige Zhang and Quanbing Liu and Li Gao and Jiaqi Shi and Haoran Xing and Teng Teng and Tian Qiu and Xinyu Zhou},
journal = {CNS neuroscience \& therapeutics},
year = {2026},
month = oct,
doi = {10.1002/cns.71202},
url = {https://europepmc.org/article/PMC/PMC13718314},
note = {CC BY},
}
RIS
TY - JOUR
TI - Plasma Lipidomic Features of Adolescent Major Depressive Disorder and Lipid Changes After Fluoxetine Treatment
AU - Chenxi Liu
AU - Yao Li
AU - Hanchen Hou
AU - Jiamei Guo
AU - Bingjie Qin
AU - Xiaoxia Xu
AU - Yuqian He
AU - Tingting Lei
AU - Fei Chen
AU - Lige Zhang
AU - Quanbing Liu
AU - Li Gao
AU - Jiaqi Shi
AU - Haoran Xing
AU - Teng Teng
AU - Tian Qiu
AU - Xinyu Zhou
PY - 2026
DA - 2026/10/29
JO - CNS neuroscience & therapeutics
DO - 10.1002/cns.71202
UR - https://europepmc.org/article/PMC/PMC13718314
AB - Background Major depressive disorder (MDD) in adolescents is a major public health concern, yet objective biological markers and treatment-related metabolic changes remain insufficiently understood. This study aimed to characterize plasma lipidomic alterations in adolescent MDD and explore lipid changes associated with fluoxetine treatment.Methods This study enrolled 75 adolescents with MDD and 75 matched healthy controls (HCs). Among the adolescents with MDD, 44 had paired baseline and week-8 plasma samples available and were included in the longitudinal analysis. Plasma lipidomic profiles were analyzed using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS).Results A total of 865 lipid species were detected. Compared with HCs, adolescents with MDD showed distinct plasma lipidomic profiles, with 82 differentially abundant lipid species identified, primarily involving triglycerides, lysophospholipids, free fatty acids, membrane phospholipids, and sphingolipids. Among the machine-learning models, logistic regression showed the highest discriminative performance, with a pooled out-of-fold AUC of 0.85 (95% CI, 0.79-0.91). Longitudinal analysis identified 21 lipid species meeting the differential criteria following fluoxetine treatment, mainly involving triglycerides and bile acid-related metabolites. Integrative pathway and target analyses suggested that fluoxetine-associated lipid changes may involve neurotransmitter signaling, inflammatory lipid metabolism, PI3K-Akt signaling, and nuclear receptor-related pathways.Conclusion This study characterizes alterations in plasma lipid metabolism in adolescent MDD and the lipidomic changes following fluoxetine treatment, providing new lipidomic evidence for candidate lipid signatures and potential treatment-associated biological pathways.Trial registration ClinicalTrials.gov, NCT05814640. Registered 20 February 2023, https://clinicaltrials.gov/study/NCT05814640.
SN - 1755-5930
SN - 1755-5949
ER -