Neural basis of GAD improvement following a mindfulness-based intervention and antidepressant treatment: an analysis from a randomized controlled trial

BACKGROUND: The brain mechanisms underlying patient improvement after interventions remain poorly understood. Identifying the shared and distinct neural pathway between improvement mechanisms across distinct treatment modalities might improve our understanding of brain-behavior relationships and inform personalized approaches. AIMS: To investigate the neural correlations of symptom improvement in Generalized Anxiety Disorder (GAD) by examining changes in brain functional connectivity (FC) following two distinct treatments: mindfulness (body-in-mind training, BMT) and fluoxetine (FLX). METHOD: Twenty GAD patients from a randomized clinical trial underwent resting-state fMRI before and after their respective interventions. FC of the amygdala with the prefrontal cortex, Default Mode (DMN), and Salience Network (SN) was analyzed. Regression analyses assessed the relationship between symptom improvement and amygdala-related FC changes. RESULTS: Increased FC between the left amygdala and right orbitofrontal cortex (OFC) was found after the interventions and associated with symptom improvement. Treatment-specific patterns of connectivity emerged: in the BMT group, symptom improvement correlated with amygdala connectivity to the DMN and SN, whereas in the FLX group, improvement was linked to amygdala-OFC coupling. However, interaction analysis did not reveal significant differences between groups. CONCLUSION: Symptom improvement in GAD may involve enhanced functional coupling between brain regions and circuits critical for emotional regulation, self-referential processing, and stimulus selection, particularly between the left amygdala and right OFC. Larger sample studies are needed to elucidate treatment-specific neural mechanisms and refine personalized therapeutic strategies.