{
  "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.\n\nObjectivesThis 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.\n\nMethodsThis 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.\n\nResultsMDD 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.\n\nConclusionAdolescent 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.",
  "abstract_shown": true,
  "affiliations": [
    "University of Electronic Science and Technology of China"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "A. F. Almulla"
    },
    {
      "name": "P. Wang"
    },
    {
      "name": "H. Mao"
    },
    {
      "name": "Y. Zhang"
    },
    {
      "name": "J. Li"
    },
    {
      "name": "J. Chen"
    },
    {
      "name": "Y. Huang"
    },
    {
      "name": "Y. Zhang"
    },
    {
      "name": "M. Maes"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6805sfrbb9z5f.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.11.26365268",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.10.11.26365268v1.full",
  "id": "6805sfrbb9z5f",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.10.11.26365268v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "medrxiv",
      "psychiatry and clinical psychology"
    ],
    [
      "openalex",
      "2802|Stress Responses and Cortisol"
    ]
  ],
  "openalex": "W7221325431",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.10.11.26365268v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-11",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/6805sfrbb9z5f.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:49Z",
      "native_id": "10.64898/2026.10.11.26365268",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.10.11.26365268v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:psychiatry and clinical psychology",
      "subfield": "psychiatry"
    }
  ],
  "title": "Reduced Systemic Homeostatic and Endothelial Protective Capacity in Adolescent Major Depression: Associations with Early-Life Adversity and Clinical Phenotypes",
  "title_text": "Reduced Systemic Homeostatic and Endothelial Protective Capacity in Adolescent Major Depression: Associations with Early-Life Adversity and Clinical Phenotypes",
  "type": "preprint",
  "updated_at": "2026-10-30T12:20:49Z",
  "url": "https://research.draconitic.com/paper/6805sfrbb9z5f",
  "venue": "medRxiv",
  "versions": []
}