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Towards Objective Major Depressive Disorder Detection: a Systematic Review and Meta-Analysis of Diagnostic Biomarkers
Zain-Ul-Abideen Gulbaz1, Shaper Mirza2, Sadiq Naveed3,4,5
1Electrical Engineering Department, Lahore University of Management Sciences, Lahore, Pakistan.
The Psychiatric Quarterly
|October 24, 2025
Summary
Identifying reliable diagnostic biomarkers for major depressive disorder (MDD) is crucial. This review highlights Interleukin-6, BDNF, cortisol, and TNF-α as promising biomarkers, though further validation is needed for clinical use.
Area of Science:
- Biomarker Discovery
- Neuroscience
- Psychiatry
Background:
- Reliable diagnostic biomarkers for major depressive disorder (MDD) are currently lacking.
- Current diagnostic methods for MDD rely heavily on clinical observation and subjective criteria.
Purpose of the Study:
- To systematically review and quantify promising diagnostic biomarkers for MDD in bodily fluids.
- To identify biomarkers with potential for clinical application in diagnosing major depressive disorder.
Main Methods:
- Comprehensive electronic literature search (PubMed, PsycINFO, ScienceDirect, Google Scholar) from 2013-2023.
- Inclusion of studies on adult human participants comparing MDD patients with healthy controls using bodily fluid biomarkers.
- Exclusion of studies on comorbid illnesses, animal models, and neuroimaging.
Main Results:
- 312 diagnostic biomarkers for MDD were identified from 175 studies.
- Interleukin-6 (IL-6), Brain-Derived Neurotrophic Factor (BDNF), cortisol, C-reactive protein (CRP), and Tumor Necrosis Factor-alpha (TNF-α) were the most frequent biomarkers.
- Meta-analysis confirmed significant associations between IL-6, BDNF, cortisol, and TNF-α with MDD.
Conclusions:
- IL-6, BDNF, cortisol, and TNF-α show potential as diagnostic biomarkers for MDD.
- Further validation across diverse populations is essential for clinical implementation.
- Future research should focus on biomarker panels and standardized methodologies to improve MDD diagnostic accuracy.
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