Predicting responses of neuromodulation and psychotherapies for major depressive disorder: A coordinate-based meta-analysis of functional magnetic resonance imaging studies

This meta-analysis synthesized resting-state functional connectivity (FC) patterns associated with treatment responses in Major Depressive Disorder (MDD). We evaluated studies from 2013 to 2023 that reported pre-treatment FC (i.e., ‘biomarker’ analysis) and/or treatment-induced FC alterations (i.e., ‘longitudinal effects’) in three treatments (i.e., transcranial magnetic stimulation, electroconvulsive therapy, psychotherapy), and further associated these patterns with gene expression, neurotransmitter distributions, and symptomatology. From 57 studies covering 1726 patients, the ‘biomarker’ results revealed significant rs-FC patterns in the Default Mode Network (DMN) and Frontoparietal Network (FPN). ‘Longitudinal effects’ were characterized by altered DMN connectivity. Psychotherapy primarily affected the visual network and DMN. Gene expression profiles explained 38.5 % and 56.0 % of the variance in ‘biomarker’ and ‘longitudinal’ results, respectively. The meta-analysis correlated with neurotransmitter distributions (e.g., serotonin, dopamine) and MDD-related terms (‘interaction’, ‘emotional’, ‘negative’). These findings indicate that baseline FC within the DMN and FPN is crucial for predicting treatment responses, and the core mechanisms may involve restoring the DMN. This work may enhance our understanding of MDD pathophysiology and help guide personalized interventions.