Dysconnectivity of a brain functional network was associated with blood inflammatory markers in depression

Abstract Objective There is increasing evidence for a subgroup of major depressive disorder (MDD) associated with heightened peripheral blood inflammatory markers. In this study, the authors sought to understand the mechanistic brainimmune axis in inflammation-linked depression by investigating associations between functional connectivity (FC) of brain networks and peripheral inflammation in depression. Methods Resting-state functional magnetic resonance imaging (fMRI) and peripheral blood immune marker data (C-reactive protein; CRP, interleukin-6; IL-6 and immune cells) were collected on N=46 healthy controls (HC; CRP ≤ 3mg/L) and N=83 cases of MDD, stratified further into low CRP (loCRP MDD; ≤ 3 mg/L; N=50) and high CRP (hiCRP MDD; > 3 mg/L; N=33). In a two-part analysis, network-based statistics (NBS) was firstly performed to ascertain FC differences via HC vs hiCRP MDD comparison. Association between this network of interconnected brain regions and peripheral CRP (N=83), IL-6 (N=72), neutrophils and CD4+ T-cells (N=36) were then examined in MDD cases only. Results Case-control NBS testing revealed a single network of abnormally attenuated FC in hiCRP MDD, chiefly comprising default mode network (DMN) and ventral attentional network (VA) coupled regions, anatomically connecting the insula/frontal-operculum and posterior cingulate cortex (PCC). Across all MDD cases, FC within the identified network scaled negatively with CRP, IL-6, and neutrophils. Conclusions The findings suggest that inflammation is associated with attenuation of functional connectivity within a brain network deemed critical for interoceptive signalling, e.g. accurate communication of peripheral bodily signals such as immune states to the brain, with implications for the etiology of inflammation-linked depression.