Reduced Systemic Homeostatic and Endothelial Protective Capacity in Adolescent Major Depression: Associations with Early-Life Adversity and Clinical Phenotypes
- 1University of Electronic Science and Technology of China
Abstract
BackgroundMajor depressive disorder (MDD) is a heterogeneous condition characterized by neuro-immune-metabolic-oxidative stress (NIMETOX) pathways. A systems-biology approach may help elucidate how these interconnected NIMETOX disturbances relate to early-life adversity and multidimensional clinical phenomes in adolescent MDD.
ObjectivesThis study aimed to define the peripheral metabolic, vascular, and acute-phase, oxidative, and lipid biomarker profiles of adolescent MDD and to investigate associations with ACEs and clinical phenotypes.
MethodsThis cross-sectional study recruited 80 adolescents with MDD and 53 matched healthy controls and assessed C-peptide and insulin, vascular tone markers, the acute-phase inflammatory axis, oxidative stress, and lipid profiles.
ResultsMDD adolescents exhibited significant reductions in C-peptide, NO, ApoE, ApoA1, HDL-C, albumin, and transferrin, together with increased ApoB/ApoA1 ratio. These biomarkers correlated significantly with family dysfunction, childhood trauma, bullying exposure, and maladaptive parenting. These biomarkers and stressors accounted for 46.2% to 61.2% of the variance in psychological resilience, and major affective, physiosomatic, self-injurious, suicidal, and self-regulation phenomes. ACEs and bullying exposure, together with relevant socio-demographic data, explained 10.5% to 28.4% of the variance in selected metabolic, vascular, and acute-phase biomarkers. Multivariable classification models showed adequate discrimination between MDD and healthy controls, achieving up to 88.5% classification accuracy and an AUC of 0.948.
ConclusionAdolescent MDD is characterized by coordinated reductions in negative acute-phase proteins, metabolic and lipoprotein protective factors, and endothelial NO, without overt CRP-defined inflammation or conventional dyslipidemia. These findings support a systems-biology model of impaired peripheral homeostatic protection associated with developmental adversity and multidimensional depressive phenomes.
Related
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BibTeX
@misc{almulla2026reduced,
title = {{Reduced Systemic Homeostatic and Endothelial Protective Capacity in Adolescent Major Depression: Associations with Early-Life Adversity and Clinical Phenotypes}},
author = {A. F. Almulla and P. Wang and H. Mao and Y. Zhang and J. Li and J. Chen and Y. Huang and Y. Zhang and M. Maes},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.11.26365268},
url = {https://www.medrxiv.org/content/10.64898/2026.10.11.26365268v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Reduced Systemic Homeostatic and Endothelial Protective Capacity in Adolescent Major Depression: Associations with Early-Life Adversity and Clinical Phenotypes
AU - A. F. Almulla
AU - P. Wang
AU - H. Mao
AU - Y. Zhang
AU - J. Li
AU - J. Chen
AU - Y. Huang
AU - Y. Zhang
AU - M. Maes
PY - 2026
DA - 2026/10/11
PB - medRxiv
DO - 10.64898/2026.10.11.26365268
UR - https://www.medrxiv.org/content/10.64898/2026.10.11.26365268v1
AB - BackgroundMajor depressive disorder (MDD) is a heterogeneous condition characterized by neuro-immune-metabolic-oxidative stress (NIMETOX) pathways. A systems-biology approach may help elucidate how these interconnected NIMETOX disturbances relate to early-life adversity and multidimensional clinical phenomes in adolescent MDD. ObjectivesThis study aimed to define the peripheral metabolic, vascular, and acute-phase, oxidative, and lipid biomarker profiles of adolescent MDD and to investigate associations with ACEs and clinical phenotypes. MethodsThis cross-sectional study recruited 80 adolescents with MDD and 53 matched healthy controls and assessed C-peptide and insulin, vascular tone markers, the acute-phase inflammatory axis, oxidative stress, and lipid profiles. ResultsMDD adolescents exhibited significant reductions in C-peptide, NO, ApoE, ApoA1, HDL-C, albumin, and transferrin, together with increased ApoB/ApoA1 ratio. These biomarkers correlated significantly with family dysfunction, childhood trauma, bullying exposure, and maladaptive parenting. These biomarkers and stressors accounted for 46.2% to 61.2% of the variance in psychological resilience, and major affective, physiosomatic, self-injurious, suicidal, and self-regulation phenomes. ACEs and bullying exposure, together with relevant socio-demographic data, explained 10.5% to 28.4% of the variance in selected metabolic, vascular, and acute-phase biomarkers. Multivariable classification models showed adequate discrimination between MDD and healthy controls, achieving up to 88.5% classification accuracy and an AUC of 0.948. ConclusionAdolescent MDD is characterized by coordinated reductions in negative acute-phase proteins, metabolic and lipoprotein protective factors, and endothelial NO, without overt CRP-defined inflammation or conventional dyslipidemia. These findings support a systems-biology model of impaired peripheral homeostatic protection associated with developmental adversity and multidimensional depressive phenomes.
ER -