The Monoamine–Glutamate Continuum of Depression: A Neurobiological Framework for Precision Psychiatry
Pietro Carmellini·Andrea Fagiolini·Alessandro Cuomo·Maria Beatrice Rescalli·Mario Pinzi·Afendra Dourmas
Background/Objectives: Major depressive disorder (MDD) remains a leading cause of disability worldwide and exhibits substantial biological heterogeneity that is not adequately captured by current symptom-based diagnostic systems. While the classical monoamine hypothesis has historically guided antidepressant development, it does not fully account for variability in treatment response, delayed therapeutic onset, or the persistence of cognitive and anhedonic symptoms. Converging evidence from mole