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 brain-immune 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. keywords: functional connectivity, network-based statistics, peripheral inflammation, immune cells, depression.

Exploring the Impact of Maternal Early Life Adversity on Interoceptive Sensibility in Pregnancy: Implications for Prenatal Depression

“…While several differences exist between pregnancy-related depression and major depressive disorder that occurs at other stages of the lifespan (Batt et al, 2020), both are characterized by core negative affective symptoms involving low or irritable mood, as well as abnormalities across numerous physiological systems (Aruldass et al, 2021;Dowlati et al, 2010;Juruena, 2014;Lamers et al, 2013;Zeng et al, 2012). A compelling and empirically supported theory is that depression, and many depressive symptoms, are primarily characterized by an underlying issue of inefficient energy regulation (Allen et al, 2018;Barrett et al, 2016;Chan et al, 2019;Shaffer et al, 2022).…”