Objectives First-line pharmacotherapy for major depressive disorder (MDD) is often insufficient. Mindfulness-based cognitive therapy (MBCT) is a promising adjunctive treatment, but its neurophysiological mechanisms are poorly understood. This study examined whether combining MBCT with treatment as usual (TAU) induces significant changes in cortical electrical activity in individuals with MDD. Method Sixty-six female participants with MDD were randomly assigned to MBCT + TAU (n = 36) or TAU (n = 30). The MBCT + TAU group completed an 8-week MBCT program alongside stable-dose citalopram (20 mg/day), while the TAU group received citalopram alone. The primary outcome was post-treatment score on the Beck Depression Inventory-II (BDI-II). Secondary outcomes included changes in power spectrum density (PSD) measured via EEG source localization using exact low-resolution electromagnetic tomography (eLORETA). Results Mean BDI score decreased from 28.08 (SD = 5.82) to 11.58 (SD = 2.57) in the MBCT + TAU group and from 27.37 (SD = 6.67) to 13.03 (SD = 3.18) in the TAU group. After adjusting for baseline scores, ANCOVA revealed a significant group effect on post-treatment BDI scores, F(1, 63) = 14.17, p < 0.001, partial η2 = 0.18. EEG analysis showed that, compared to TAU, the MBCT + TAU group exhibited significantly decreased theta power and increased upper alpha and low beta power post-treatment in regions suggestive of insula and frontal cortex involvement (corrected p < 0.05). Conclusions Combining MBCT with TAU reduces depressive symptoms and induces beneficial changes in cortical electrical activity in women with MDD. These findings support integrating MBCT into standard treatment protocols for MDD.

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