Limbic gray matter increases in response to cognitive-behavioral therapy in major depressive disorder

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Abstract

Major depressive disorder (MDD) is related to volumetric decreases in (cortico-)limbic brain regions. In contrast to pharmacological and electroconvulsive therapy, little is known about the brain structural effects of psychotherapy and potential links to symptom improvements. In a naturalistic longitudinal study using structural magnetic resonance tomography, gray matter volume (GMV) and clinical measures were assessed in 30 outpatients with MDD before and after 20 cognitive-behavioral therapy (CBT) sessions. Data from 30 healthy controls was acquired. Region-of-interest analyses revealed significant GMV increases within patients for the right anterior hippocampus and the bilateral amygdala, resulting in a significant group-by-time interaction for the left amygdala (p ≤ 0.022). Simultaneously, analyses revealed volumetric decreases in the right posterior hippocampus (p = 0.016). While there were no associations with overall symptom improvement, right amygdala volume increases were slightly associated with improvements in identifying feelings (rs = 0.321, p = 0.042). Together, findings show an impact of CBT not only on psychopathology but also on brain structure. The connection between CBT-related increased amygdala GMV and improved emotion identification emphasizes the role of improvements in emotional awareness.

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Zwiky, E., Borgers, T., Klug, M., König, P., Schöniger, K., Selle, J., … Redlich, R. (2025). Limbic gray matter increases in response to cognitive-behavioral therapy in major depressive disorder. Translational Psychiatry, 15(1). https://doi.org/10.1038/s41398-025-03545-7

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