Multi-brain network functional connectivity in major depressive disorder: a fMRI systematic review of mechanisms and clinical translation.

Major Depressive Disorder (MDD) poses significant health risks, yet diagnosis lacks objective biomarkers. This systematic review synthesizes functional Magnetic Resonance Imaging (fMRI) studies (2020-2025, n = 52) on functional connectivity (FC) in MDD. We found robust FC alterations within and between core networks (Default Mode, Salience, Central Executive), linked to rumination, emotion dysregulation, and cognitive deficits. These alterations varied with suicidal ideation, comorbidities, childhood trauma, and biological sex. Treatments (antidepressants, rTMS, ECT) demonstrated distinct normalization effects on specific networks. This review consolidates evidence for MDD as a "network interaction disorder," moving beyond single-network foci. It highlights the translational potential of fMRI-based FC for refining diagnosis, personalizing treatment, and provides a novel integrative framework for future researches.