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

Childhood trauma (CT), defined as emotional, physical or sexual abuse or emotional or physical neglect before the age of 18, is a major risk factor for major depressive disorder (MDD), potentially via altered stress system development. Among individuals with MDD, CT is linked to widespread alterations in resting-state functional connectivity, including reduced functional connectivity and altered brain network properties within the prefrontal-limbic-thalamic-cerebellar circuit [1, 2] and increased functional connectivity within the default mode network [3]. However, prior research has predominantly focused on fronto-limbic circuits, either in the absence of a stressor or exclusively during the acute stress response, while data on changes in whole-brain resting-state functional connectivity over time following stress induction in this population is lacking. Therefore, this study examined stress-response network dynamics in individuals with MDD and CT by assessing changes in network centrality based on resting-state functional magnetic resonance imaging scans during acute and delayed stress phases following a standardized stress induction paradigm compared to healthy individuals without CT.

Resting-state functional magnetic resonance imaging (fMRI) was acquired during acute (15 min post-stressor) and delayed (135 min post-stressor) stress phases following the Trier Social Stress Test (TSST) in 66 adults with MDD and CT and 33 controls. Subjective stress and affect were measured using visual analog scales. Network centrality was primarily assessed using eigenvector centrality (EC), a graph-theoretic measure that captures the importance of a node within a network by considering both its direct connections and the extent to which those nodes are connected within the network (i.e., their centrality) [4, 5]. In addition, degree centrality (DC) was computed as a simpler centrality measure that reflects a node’s direct connections without taking into account the connections to its neighboring nodes [4]. Voxel-wise EC and DC mapping quantified the network importance of eight functional brain networks.

Both groups showed significant subjective stress responses, with greater increases in tension in the MDD with CT group as compared to controls. While both groups reported increased negative affect following stress, reactivity did not differ between groups. 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. Consistently, no significant changes in DC across time were observed for any network within either group, nor any group × time interactions. However, DC was significantly lower in the MDD with CT group compared to controls across all eight networks.

No stress-related changes in large-scale resting-state network centrality were observed, suggesting that this global measure may not be a sensitive indicator of stress-related vulnerability in MDD and CT. However, subjective stress responses and overall DC did distinguish groups, underscoring the value of studying CT within a broader, multimodal context. Future studies incorporating task-based paradigms and biological markers are warranted to elucidate the neural and behavioral pathways linking MDD, CT, and stress reactivity.

References

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