Chronicity moderates the impact of severity on Central Executive - Default Mode Network functional interactions in Depression

Neuroimaging has revealed that major depression is underpinned by dysfunctional brain networks, with symptom variability stemming from altered interactions within and between brain regions. While the effect of depression severity is well-studied, the effect of depression duration (chronicity) is relatively neglected, despite its clinical significance. This study examined how severity, chronicity, and their interaction affect brain network connectivity and grey matter volume. Forty-six patients (31 females, mean age 40.5) were assessed using whole-brain network modeling and voxel-based morphometry (VBM). Severity was measured via the Hamilton Depression Rating Scale, and chronicity was defined as an episode lasting over 24 months. The key finding was that chronicity moderated the impact of severity on functional connectivity between the Central Executive Network (CEN) and the precuneus (part of the Default Mode Network, DMN). Chronic versus non-chronic patients showed opposite patterns. Non-chronic patients showed stronger CEN-Default Mode Precuneus connectivity at low severity and weaker at high severity; chronic patients showed the reverse. This study reveals a novel impact of chronicity on CEN-DMN interactions, a neglected moderator of brain-symptom severity correlations in depression.