Antidepressant effects of intermittent theta-burst stimulation are associated with lower baseline regional gray matter volumes and surface areas in prefrontal cortex

Journal article

Introduction: Major depressive disorder (MDD) is a leading cause of disability worldwide. Intermittent theta-burst stimulation (iTBS) is an effective neuromodulation treatment for MDD, yet treatment response varies and its mechanisms remain unclear. Individual differences in cortical morphology in regions linked to depression may influence treatment outcomes.

Objective: To investigate whether baseline cortical morphology, specifically gray matter volumes (GMV), surface area (SA) and cortical thickness (CT) of the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC), are predictive to clinical response to a validated iTBS treatment for MDD.

Methods: As part of the BRAEN-MAP trial, fifty-nine patients with MDD underwent daily iTBS sessions targeting the left DLPFC. Depressive symptoms were assessed weekly using the 17-item Hamilton Depression Rating Scale (HDRS-17). Pretreatment structural MRI data were processed with FreeSurfer to extract GMV, SA, and CT from bilateral DLPFC and ACC. Associations with symptom improvement were tested using mixed linear models.

Results: Fifty patients (mean age = 39.98 years, SD=10.79; 84.6% female) were included in the analysis. HDRS-17 scores decreased from 18.23 (SD=2.67) to 8.0 (SD=5.1) after six weeks. Smaller baseline GMV in the left DLPFC (area p9-46v) and right pregenual ACC (area s32), as well as reduced SA in bilateral DLPFC (p9-46v, 8C, a9-46v, 46, 8Av, i6.8) and ACC subregions (s32, d32, 25, a32pr), were significantly associated with greater symptom improvement. No associations were found for CT.

Conclusion: A significant association between individual cortical morphology and depression improvement after iTBS was seen, showing that variations in pretreatment cortical structure may influence neuromodulation treatment efficacy.

Authors: Cavendish, BA; Suen, P; da Silva, PHR; Sarrazin, V; Baptista, M

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Journal: Journal of Psychiatric Research
• Volume: 193
• Pages: 179-187
• Publication date: 2025-11-07
• Acceptance date: 2025-11-07
• DOI: 10.1016/j.jpsychires.2025.11.006
• EISSN: 1879-1379
• ISSN: 0022-3956
• Language: English
• Keywords: major depressive disorder; intermittent theta-burst stimulation; cortical morphology; gray matter volume; cortical thickness; surface area