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MRI-guided dmPFC-rTMS as a Treatment for Treatment-resistant Major Depressive Disorder

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Treatment-characteristic brain structural changes in depression: A multi-center longitudinal observational study.

Momoko Hatakoshi¹, Naoya Oishi², Yujiro Yoshihara¹

¹Department of Psychiatry, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Journal of Affective Disorders

|July 15, 2026

Summary

Brain structure changes during depression treatment vary by method. Electroconvulsive therapy (ECT) and antidepressant medication (ADM) showed gray matter volume (GMV) increases, unlike cognitive behavioral therapy (CBT) or repetitive transcranial magnetic stimulation (rTMS).

Keywords:

Biomarker Depressive disorder Gray matter volume Insula Longitudinal Neuroimaging Treatment-related

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Area of Science:

Neuroscience
Neuroimaging
Psychiatry

Background:

The neurobiological underpinnings of depression remission across different treatments are not well understood.
Investigating temporal gray matter volume (GMV) changes offers insight into treatment-specific effects.

Purpose of the Study:

To examine longitudinal GMV changes in depression patients undergoing four distinct treatment modalities: antidepressant medication (ADM), cognitive behavioral therapy (CBT), electroconvulsive therapy (ECT), and repetitive transcranial magnetic stimulation (rTMS).
To correlate GMV alterations with clinical symptom changes.

Main Methods:

A multi-center, longitudinal observational study involving 155 depression patients and 152 healthy controls.
Magnetic resonance imaging (MRI) and clinical assessments were conducted at pre-treatment, post-treatment, and 6-month follow-up.
Voxel-based morphometry analyzed baseline GMV differences and longitudinal changes, with ComBat harmonization for scanner effects.

Main Results:

Depression patients initially had lower GMV in the hippocampus, amygdala, thalamus, insula, and middle frontal gyrus compared to controls.
ECT and ADM groups exhibited significant GMV changes; ECT showed increases in the hippocampus, amygdala, and insula, while ADM showed transient insular changes.
No significant GMV changes were observed in CBT or rTMS groups. Later-phase insular GMV reduction in ADM correlated with symptom worsening.

Conclusions:

Despite clinical improvement across all treatments, distinct patterns of structural brain changes were observed, suggesting modality-specific neurobiological effects.
Later-phase insular GMV reduction may serve as a potential biomarker for long-term treatment response in antidepressant medication therapy.