Replicable Connectivity and Spectral Alterations of Functional Networks in Major Depression

Major depressive disorder (MDD) is usually characterized in functional MRI through connectivity alone, often in samples too small to resolve its modest effects. Here we applied multi-scale, template-guided independent component analysis to resting-state data from the multi-site MDD-DIRECT cohort and jointly examined the connectivity, spectral content and spatial composition of 105 intrinsic brain networks. Differences between patients and controls were widespread, small and structured: cerebello-subcortical coupling was reduced, subcortical--somatomotor coupling was increased, and spectral power shifted from lower to higher frequencies, most prominently in the thalamus, which also showed the most altered connectivity. Spatial composition differed in every network examined. In a smaller independent cohort, the direction of effect agreed for 95% of significant connections, 78% of significant spectral effects and 77% of the largest spatial-composition effects. Depression therefore alters several distinct properties of intrinsic networks, consistently across cohorts and most prominently in the thalamus.