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Updated: Feb 5, 2026

MRI-guided dmPFC-rTMS as a Treatment for Treatment-resistant Major Depressive Disorder
Published on: August 11, 2015
Longitudinal brain volume changes in major depressive disorder
Dilara Yüksel1, Jennifer Engelen2, Verena Schuster2
1Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Rudolf-Bultmann-Str. 8, 35039, Marburg, Germany. dilara.yueksel@med.uni-marburg.de.
Abstract:
Patients with major depressive disorder (MDD) exhibit gray matter volume (GMV) reductions in limbic regions. Clinical variables-such as the number of depressive episodes-seem to affect volume alterations. It is unclear whether the observed cross-sectional GMV abnormalities in MDD change over time, and whether there is a longitudinal relationship between GMV changes and the course of disorder. We investigated T1 structural MRI images of 54 healthy control (HC) and 37 MDD patients in a 3-Tesla-MRI with a follow-up interval of 3 years. The Cat12 toolbox was used to analyze longitudinal data (p < 0.05, FWE-corrected, whole-brain analysis; flexible factorial design). Interaction effects indicated increasing GMV in MDD in the bilateral amygdala, and decreasing GMV in the right thalamus between T1 and T2. Further analyses comparing patients with a mild course of disorder (MCD; 0-1 depressive episode during the follow-up) to patients with a severe course of disorder (SCD; > 1 depressive episode during the follow-up) revealed increasing amygdalar volume in MCD. Our study confirms structural alterations in limbic regions in MDD patients and an association between these impairments and the course of disorder. Thus, we assume that the reported volumetric alterations in the left amygdala (i.e. volumetric normalization) are reversible and apparently driven by the clinical phenotype. Hence, these results support the assumption that the severity and progression of disease influences amygdalar GMV changes in MDD or vice versa.
Insights
Major depressive disorder (MDD) patients show reversible gray matter volume changes in the amygdala, linked to the disorder's course. These findings suggest disease severity influences brain structure over time.
Area of Science:
- Neuroimaging
- Psychiatry
- Neuroscience
Background:
- Major depressive disorder (MDD) is associated with gray matter volume (GMV) reductions in limbic regions.
- Clinical factors like depressive episode count may influence GMV alterations.
- Longitudinal changes in GMV and their relationship to MDD progression remain unclear.
Purpose of the Study:
- To investigate longitudinal GMV changes in MDD patients over a 3-year period.
- To explore the relationship between GMV alterations and the course of the disorder.
- To determine if structural abnormalities in MDD are dynamic and influenced by clinical phenotype.
Main Methods:
- Utilized T1 structural MRI scans from 54 healthy controls (HC) and 37 MDD patients.
- Employed a 3-Tesla MRI scanner with a 3-year follow-up interval.
- Analyzed longitudinal data using the Cat12 toolbox with whole-brain analysis (FWE-corrected, p<0.05).
Main Results:
- MDD patients showed increasing GMV in the bilateral amygdala and decreasing GMV in the right thalamus over 3 years.
- Patients with a mild course of disorder (MCD) exhibited increased amygdalar volume.
- A significant association was found between GMV changes and the course of MDD.
Conclusions:
- Structural alterations in limbic regions are confirmed in MDD patients.
- Volumetric changes in the amygdala appear reversible and linked to the clinical course of MDD.
- Disease severity and progression significantly influence amygdalar GMV changes in MDD.
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