Kynurenine pathway modulates dynamic network instability and depression severity in major depressive disorder

This study investigates changes in dynamic functional connectivity (dFC) within the default mode, salience, and central executive networks in adults with Major Depressive Disorder (MDD). Additionally, it seeks to explore the associations between these alterations and kynurenine pathway metabolites, as well as their impact on depression severity.

Resting-state functional magnetic resonance imaging was used to assess dFC in 53 MDD patients and 58 matched healthy controls. Plasma levels of kynurenine (KYN), kynurenic acid, and quinolinic acid were measured. Analyses were conducted to identify differences in dFC metrics and to examine correlations among dFC, KYN metabolites, and depression severity.

Four distinct dFC states were identified, and MDD patients exhibited a higher frequency of state transitions compared to healthy controls (MDD: 13.49 ± 3.25 vs. HC: 10.98 ± 3.81, p < 0.001). Additionally, plasma KYN levels were found to be negatively correlated with transition frequency in MDD patients (r = -0.333, p = 0.015). Importantly, KYN levels significantly moderated the relationship between the number of state transitions and depression severity (B = -0.018, SE = 0.005, p < 0.001).

MDD patients experience more frequent state changes in the triple network's dynamic functional connectivity, and the interaction between KYN levels and dynamic network instability significantly affects depression severity.