Childhood abuse influences clinical features of major depressive disorder by modulating the functional network of the right amygdala subregions

Abstract

Childhood trauma and the amygdala play essential roles in major depressive disorder (MDD) mechanisms. However, the neurobiological mechanism among them remains unclear. Therefore, we explored the relationship among the amygdala subregion's abnormal functional connectivity (FC), clinical features, and childhood trauma in MDD. We obtained resting-state functional magnetic resonance imaging (fMRI) in 115 MDD patients and 91 well-matched healthy controls (HC). Amygdala subregions were defined according to the Human Brainnetome Atlas. The case vs. control difference in FCs was extracted. After controlling for age, sex, and education years, the mediations between the detected abnormal FCs and clinical features were analyzed, including the onset age of MDD and the Hamilton Depression Scale-24 (HAMD-24) reductive rate. Compared with HC subjects, we found, only the right amygdala subregions, namely the right medial amygdala (mAmyg.R) and the right lateral amygdala (lAmyg.R), showed a significant decrease in whole-brain FCs in MDD patients. Only childhood abuse experiences were significantly associated with amygdala subregion connectivity and clinical features in MDD patients. Additionally, The FCs between the mAmyg.R and extensive frontal, temporal, and subcortical regions mediated between the early life abuses and disease onset or treatment outcome. The findings indicate that the abnormal connectivity of the right amygdala subregions is involved in MDD's pathogenesis and clinical characteristics.