Cognitive behavioral therapy may have a rehabilitative, not normalizing, effect on functional connectivity in adolescent depression

Abstract

Background: Whether the differences in brain structure and function, characteristic of adult major depressive disorder (MDD¹), are present in adolescent MDD is still unclear, but it has been shown that cognitive behavioral therapy (CBT²) affects resting-state functional connectivity in both adult and adolescent MDD patients, with the claim that CBT has a normalizing effect on MDD-related functional disruption, but this has not been directly tested.

Methods: 128 adolescent MDD patients and 40 adolescent controls were enrolled in the study. We investigated pre-treatment differences in cortical thickness, white matter volume, and resting-state functional connectivity. We also investigated the longitudinal effects of CBT on resting-state functional connectivity, and the relationship between pre-treatment functional disruption and CBT-related changes to resting-state functional connectivity was assessed by the correlation of pre-treatment cross-sectional effects and longitudinal CBT-related effects across multiple brain regions.

Results: Patients had greater cortical thickness and white matter volume within fronto-limbic regions of the brain. Patients had greater pre-treatment resting-state functional connectivity within the default-mode, fronto-limbic, central-executive, and salience networks. CBT increased resting-state functional connectivity of the subgenual anterior cingulate and amygdala seeds with predominantly frontal regions. Regions showing the greatest pre-treatment functional disruption showed the weakest CBT-related changes.

Limitations: For ethical reasons, there was no placebo group.

Conclusions: Adolescent MDD is associated with structural and functional differences also seen in adult patients. CBT-related changes in resting-state functional connectivity do not appear to show a normalizing effect, but instead indicate rehabilitative effects on resting-state functional connectivity.

Keywords: Adolescent depression; CBT; Cortical thickness; MRI; Resting-state functional connectivity; White matter volume.