Cognitive Behavioral Therapy Lowers Elevated Functional Connectivity in Depressed Adolescents

Imaging studies have implicated altered functional connectivity in adults with major depressive disorder (MDD). Whether similar dysfunction is present in adolescent patients is unclear. The degree of resting-state functional connectivity (rsFC) may reflect abnormalities within emotional (‘hot’) and cognitive control (‘cold’) neural systems. Here, we investigate rsFC of these systems in adolescent patients and changes following cognitive behavioral therapy (CBT). Functional Magnetic Resonance Imaging (fMRI) was acquired from adolescent patients before CBT, and 24-weeks later following completed therapy. Similar data were obtained from control participants. Cross-sectional Cohort: From 82 patients and 34 controls at baseline, rsFC of the amygdala, anterior cingulate cortex (ACC), and pre-frontal cortex (PFC) was calculated for comparison. Longitudinal Cohort: From 17 patients and 30 controls with longitudinal data, treatment effects were tested on rsFC. Patients demonstrated significantly greater rsFC to left amygdala, bilateral supragenual ACC, but not with PFC. Treatment effects were observed in right insula connected to left supragenual ACC, with baseline case-control differences reduced. rsFC changes were significantly correlated with changes in depression severity. Depressed adolescents exhibited heightened connectivity in regions of ‘hot’ emotional processing, known to be associated with depression, where treatment exposure exerted positive effects, without concomitant differences in areas of ‘cold’ cognition. •Adjunct study to a large randomized multicentre UK trial of conversational therapies•Robust pre-processing methods reduced head motion artefacts, improving upon those undertaken by the majority of studies.•Aberrant processing in ‘hot’ limbic regions without reductions in cognitive control in ‘cold’ prefrontal regions was found.•Elevated limbic functional connectivity in patients was lowered towards values seen in controls following CBT. This study demonstrates that unlike depressed adults, adolescents have aberrant brain connectivity in regions associated with emotional processing without concomitant differences in areas associated with cognitive control. Moreover, cognitive behavioral therapy restored such aberrant brain connectivity. The brain is thus malleable to conversational therapy, with the degree of change related to improvement in symptoms. This gives the hope that kindling effects – whereby episodes of illness increase vulnerability t