Functional connectivity between the habenula and posterior default mode network contributes to the response of the duloxetine effect in major depressive disorder.

This study aims to investigate the functional connectivity (FC) changes of the habenula (Hb) among patients with major depressive disorder (MDD) after 12 weeks of duloxetine treatment (MDD12). Patients who were diagnosed with MDD for the first time and were drug-naïve were recruited at baseline as cases. Healthy controls (HCs) matched for sex, age, and education level were also recruited at the same time. At baseline, all participants underwent resting-state functional MRI. FC analyses were performed using the Hb seed region of interest, and three groups including HCs, MDD group and MDD12 group were compared using whole-brain voxel-wise comparisons. Compared to the HCs, the MDD group had decreased FC between the Hb and the right anterior cingulate cortex at baseline. Compared to the HCs, the FC between the Hb and the left medial superior frontal gyrus decreased in the MDD12 group. Additionally, the FC between the left precuneus, bilateral cuneus and Hb increased in the MDD12 group than that in the MDD group. No significant correlation was found between HDRS-17 and the FC between the Hb, bilateral cuneus, and the left precuneus in the MDD12 group. Our study suggests that the FC between the post-default mode network and Hb may be the treatment mechanism of duloxetine and the treatment mechanisms and the pathogenesis of depression may be independent of each other.