Brain network dysfunction and treatment-induced network reorganization in major depressive disorder

The present study aimed to investigate the characteristics of abnormal resting-state brain-network connectivity and the reorganization effects of antidepressant drug escitalopram oxalate treatment in patients with major depressive disorder (MDD), and to explore spatial correlations between brain network alterations and gene expression profiles. We employed a longitudinal study design to recruit 113 patients with MDD and 114 healthy controls (HCs) between November 2020 and October 2022. Clinical symptoms were assessed using the 17-item Hamilton Depression Scale (HAMD-17). Resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired using a Siemens 3.0 T MRI scanner. At baseline, patients with MDD exhibited significantly reduced functional connectivity (FC) within the default mode network (DMN) compared to HCs, along with significantly increased FC between the sensorimotor network (SMN) and both the frontoparietal network (FPN) and the salience network (SN) (False Discovery Rate, FDR-corrected, p < 0.05). Following treatment with escitalopram oxalate, MDD patients showed a significant enhancement in intra-DMN connectivity, as well as a significant reduction in SMN-FPN and SMN-SN connectivity (FDR-corrected, p < 0.05). Notably, the degree of increase in intra-DMN connectivity was significantly and negatively correlated with improvement in core depressive symptoms (r = - 0.305, p = 0.026), while the reduction in SMN-DMN connectivity was positively correlated with the alleviation of somatic symptoms (r = 0.362, p = 0.008). Further neuroimaging-guided transcriptomics analysis indicated that these alterations in brain network connectivity were linked to biological pathways, such as the Wnt signaling. In conclusion, our findings demonstrate a multidimensional imbalance in brain network connectivity in MDD and show that antidepressant treatment can partially ameliorate aberrant connectivity patterns. These neural changes are closely associated with symptomatic improvements, offering valuable imaging-based evidence for understanding the neurobiological mechanisms of MDD and informing the development of personalized treatment strategies.