Impact of inflammation on white matter integrity and functional connectivity in chronic major depressive disorder.

Publication date: Jul 07, 2025

Inflammation is increasingly recognized as a pathophysiologic component of major depressive disorder (MDD). Concurrently, depressive episode chronicity has emerged as a significant predictor of adverse long-term outcomes. Utilizing data from the Predictors of Remission in Depression to Individual and Combined Treatments (PReDICT) study, our analysis included 201 participants who completed C-reactive protein (CRP) sampling and diffusion-weighted imaging scans, of whom 120 participants had usable functional magnetic resonance imaging scans. Chronicity was classified as the presence of a current depressive episode ≥2 years in duration. We examined the impact of inflammation on brain structure and function in MDD, focusing specifically on differences related to chronicity, as well as the interactions between inflammation, functional, and structural alterations. No significant correlations were observed between CRP concentrations and either functional connectivity (FC) or fractional anisotropy (FA). In chronic, but not non-chronic, MDD patients, higher CRP concentrations were associated with lower FA in several neural pathways, including cingulum and frontal aslant tracts. Significant CRP by MDD chronicity interactions were also observed for FC within the default mode network (DMN) and the salience network (SN). Moreover, mediation analyses demonstrated both direct and FA-mediated effects of CRP on FC within the SN in chronic patients. Interactions based on depressive episode chronicity between CRP and neurobiological function, potentially mediated by reductions in WM integrity, suggest a potential pathophysiological process in some chronic MDD patients. The differences in FC suggest specific compensatory adjustments within DMN and SN among chronic MDD patients.

Semantics

Original Article