Functional connectivity changes between amygdala and prefrontal cortex after ECT are associated with improvement in distinct depressive symptoms

Electroconvulsive therapy (ECT) is one of the most effective treatments for treatment-resistant depression. However, the underlying mechanisms of action are not yet fully understood. The investigation of depression-specific networks using resting-state fMRI and the relation to differential symptom improvement might be an innovative approach providing new insights into the underlying processes. In this naturalistic study, we investigated the relationship between changes in resting-state functional connectivity (rsFC) and symptom improvement after ECT in 21 patients with treatment-resistant depression. We investigated rsFC before and after ECT and focused our analyses on FC changes directly related to symptom reduction and on FC at baseline to identify neural targets that might predict individual clinical responses to ECT. Additional analyses were performed to identify the direct relationship between rsFC change and symptom dimensions such as sadness, negative thoughts, detachment, and neurovegetative symptoms. An increase in rsFC between the left amygdala and left dorsolateral prefrontal cortex (DLPFC) after ECT was related to overall symptom reduction (Bonferroni-corrected p = 0.033) as well as to a reduction in specific symptoms such as sadness (r = 0.524, uncorrected p = 0.014), negative thoughts (r = 0.700, Bonferroni-corrected p = 0.002) and detachment (r = 0.663, p = 0.004), but not in neurovegetative symptoms. Furthermore, high baseline rsFC between the left amygdala and the right frontal pole (FP) predicted treatment outcome (uncorrected p = 0.039). We conclude that changes in FC in regions of the limbic-prefrontal network are associated with symptom improvement, particularly in affective and cognitive dimensions. Frontal-limbic connectivity has the potential to predict symptom improvement after ECT. Further research combining functional imaging biomarkers and a symptom-based approach might be promising. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00406-023-01552-7.