Brain network centrality following stress in adults with major depressive disorder and childhood trauma

Childhood trauma (CT) is a major risk factor for major depressive disorder (MDD), potentially via altered stress system development. Previous studies have shown stress-related changes in brain network function in clinical populations, but evidence in MDD with CT remains scarce. This study examined changes in functional brain networks in adults with MDD and CT during acute and delayed phases following stress.

Resting-state functional magnetic resonance imaging (fMRI) was acquired during acute (15 min) and delayed (135 min) stress phases following the Trier Social Stress Test in 66 adults with MDD and CT and 33 controls. Voxel-wise eigenvector centrality (EC) mapping quantified the network importance of eight functional brain networks. Subjective stress and affect were measured using visual analog scales.

Both groups showed significant subjective stress responses, with greater increases in tension in the MDD + CT group; affective reactivity did not differ. No significant changes in EC were observed between acute and delayed phases in any network, nor were there main effects of group or group × time interactions. Sensitivity analyses in severe MDD and multiple CT subtypes confirmed these null findings.

Network centrality did not differentiate individuals with MDD and CT from controls following stress, while subjective tension responses were higher in the MDD + CT group. These results suggest that global resting-state network centrality may not be a sensitive indicator of stress vulnerability following CT. Future multimodal studies incorporating task-based paradigms and biological markers are warranted to elucidate the neural and behavioral pathways linking MDD, CT, and stress reactivity.