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

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.