Effective Connectivity of Right Amygdala Subregions Predicts Symptom Improvement Following 12-Week Pharmacological Therapy in Major Depressive Disorder

The low rates of treatment response still exist in the pharmacological therapy of major depressive disorder (MDD). Exploring an optimal neurological predictor of symptom improvement caused by pharmacotherapy is urgently needed for improving response to treatment. The amygdala is closely related to the pathological mechanism of MDD and is expected to be a predictor of the treatment. However, previous studies ignored the heterogeneousness and lateralization of amygdala. Therefore, this study mainly aimed to explore whether the right amygdala subregion function at baseline can predict symptom improvement after 12-week pharmacotherapy in MDD patients. We performed granger causality analysis (GCA) to identify abnormal effective connectivity (EC) of right amygdala subregions in MDD and compared the EC strength before and after 12-week pharmacological therapy. The results show that the abnormal EC mainly concentrated on the frontolimbic circuitry and default mode network (DMN). With relief of the clinical symptom, these abnormal ECs also change toward normalization. In addition, the EC strength of right amygdala subregions at baseline showed significant predictive ability for symptom improvement using a regularized least-squares regression predict model. These findings indicated that the EC of right amygdala subregions may be functionally related in symptom improvement of MDD. It may aid us to understand the neurological mechanism of pharmacotherapy and can be used as a promising predictor for symptom improvement in MDD.