Reductions in limbic activity during negative emotion processing following cognitive-behavioural therapy in depressive disorders

Cognitive-behavioural therapy (CBT) is a first-line treatment for depressive disorders. Currently, research on the neurobiological mechanisms driving CBT remains limited. Given the heterogeneity in CBT response, investigating the neurobiological effects of CBT may improve prediction of response and treatments. In this naturalistic study, 59 patients with depressive disorders were investigated before and after 20 CBT sessions using a negative emotion processing paradigm during fMRI, clinical interviews, and depressive symptom questionnaires. Healthy controls (n=60) were also assessed twice within an equivalent time interval. Based on affective state changes during CBT, patients were divided into subgroups (n=40 responder, n=19 non-responder). Changes in brain activity and clinical outcome were examined using group × time ANOVAs for limbic areas and at whole-brain level. Patients showed significant hippocampal and dorsal anterior cingulate cortex activity decreases during negative emotion processing post-CBT (pFWE≤.024), with no changes observed in healthy controls. Hippocampal activity decreases were driven by responder (pFWE≤.020) and correlated with symptom improvement (r=.293, p=.024). Responder also exhibited higher pre-treatment hippocampal activity (pFWE=.017). CBT led to reduced activity in emotion processing regions in patients with depressive disorders, with changes in hippocampal activity linked to CBT response. This suggests depression-specific brain activity improves after successful CBT, possibly due to corrected biased emotion processing mediated by altered activity within key areas of emotion processing. Aligning with cognitive depression models, these changes could disrupt the cycle of negative emotion processing, low mood, and brain changes. Furthermore, heightened pre-treatment hippocampal activity may function as a predictive marker for CBT response.