Improve cognition of depressive patients through the regulation of basal ganglia connectivity: Combined medication using Shuganjieyu capsule.

Shuganjieyu capsule (Shugan) is a combined extract of Hypericum perforatum (HP) and Eleutherococcus senticosus (ES). Both HP and ES have been proven effective in the treatment of depression and impaired cognition. However, for mild to moderate depression (MMD), the treatment effect and underlying mechanism by combining both HP and ES are largely unknown. Here, we aim to evaluate the therapeutic effects on impaired cognition using Shugan, a combined medication of HP and ES. Resting-state magnetic resonance imaging (MRI) data and cognitive assessment have been collected from 54 healthy controls and 55 MMD patients that have been undergoing 8-week Shugan-treatment. The functional connectivity (FC) and brain region volume changes of the basal ganglia seeded circuit have been measured, and their relation with the cognitive assessment score was calculated. After that, a literature-based pathway analysis has been conducted to explore the biological relations among Shugan, brain regions, and depression. Compared to healthy controls, MMD patients demonstrated a significantly higher FC (P= 0.0025) between right ventral caudate (vCa) and left orbitofrontal cortex (OFC), which was decreased after the treatment (P < 0.001). A volume of the right caudate, which is increased in MMD, has also been reduced by Shugan treatment (P= 0.017). Importantly, the cognitive scores were strongly correlated with both Shugan treatment and the FC between vCa and OFC (r= 0.321, P= 0.02). Besides, we identified multiple signaling pathways, through which Shugan might improve the cognition of MMD patients. Our results support the therapeutic effects of Shugan on cognition in MMD, which may be realized partly through the regulation within two brain regions, vCa and OFC.