A Reproducible Neurobiology of Depressive Rumination

Depressive Rumination (DR), which involves a repetitive focus on ones distress, has been linked to alterations in functional connectivity of the triple-network, consisting of Default-Mode, Salience, and Executive Control networks. A structural basis for these functional alterations that can dually explain DRs persistence as a stable trait remains unexplored, however. Using diffusion and functional MRI, we investigated multimodal relationships between DR severity, white-matter (WM) microstructure, and resting-state functional connectivity in depressed adults, and then directly replicated our results in a phenotypically-matched, independent sample (total N = 78). Among the fully-replicated findings, DR severity was associated with: (a) global microstructure of the right Superior Longitudinal Fasciculus and local microstructure of distributed primary-fiber and crossing-fiber WM; (b) a functional connectivity imbalance of segregation and integration within the triple-network; and (c) multi-layer associations between these microstructural and functional connectivity biomarkers. Taken together, our results provide the first reproducible evidence for a multivariate microstructural-functional basis of rumination in the depressed brain.