The multi-algorithm machine learning approach identified a consensus three-gene diagnostic panel comprising SLC4A1, IGF1, and MMP9, which achieved a high classification accuracy with an Area Under the Curve (AUC) of 0.867.<h4>Conclusion</h4>This study delineates a systemic molecular landscape of adolescent MDD defined by the coexistence of hypoxic compensation and neurotrophic/remodeling failure. This evidence concerns the gene IGF1 and major depressive disorder.