Aruldass, A. R. et al. (2021) Dysconnectivity of a brain functional network was associated with blood inflammatory markers in depression. Brain, Behavior, and Immunity, 98, pp. 299-309. (doi: 10.1016/j.bbi.2021.08.226) (PMID:34450247)
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Abstract
Objective: There is increasing evidence for a subgroup of major depressive disorder (MDD) associated with heightened peripheral blood inflammatory markers. In this study, we aimed to understand the mechanistic brain-immune axis in inflammation-linked depression by investigating associations between functional connectivity (FC) of brain networks and peripheral blood immune markers in depression. Methods: Resting-state functional magnetic resonance imaging (fMRI) and peripheral blood inflammatory markers (C-reactive protein; CRP, interleukin-6; IL-6 and immune cells) were collected on N = 46 healthy controls (HC; CRP ≤ 3 mg/L) and N = 83 cases of depression, stratified further into low CRP cases (loCRP cases; ≤ 3 mg/L; N = 50) and high CRP cases (hiCRP cases; > 3 mg/L; N = 33). In a two-part analysis, network-based statistics (NBS) was firstly used to ascertain whole-brain FC differences in HC vs hiCRP cases. Secondly, we investigated the association between this network of interconnected brain regions and continuous measures of peripheral CRP (N = 83), IL-6 (N = 72), neutrophils and CD4+ T-cells (N = 36) in depression cases only. Results: Case-control NBS testing revealed a single network of abnormally attenuated FC in the high CRP depression cases compared to healthy controls. Connections within this network were mainly between brain regions located in the left insula/frontal operculum and posterior cingulate cortex, which were assigned to ventral attention and default mode canonical fMRI networks respectively. Within-group analysis across all depression cases, secondarily demonstrated that FC within the identified network significantly negatively scaled with CRP, IL-6 and neutrophils. Conclusions: The findings suggest that inflammation is associated with disruption 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 pathogenesis of inflammation-linked depression.
| Item Type: | Articles |
|---|---|
| Keywords: | Depression, network-based statistics, inflammation, functional connectivity. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Cavanagh, Professor Jonathan |
| Authors: | Aruldass, A. R., Kitzbichler, M. G., Morgan, S. E., Lim, S., Lynall, M.-E., Turner, L., Vertes, P., Cavanagh, J., Cowen, P., Pariante, C. M., Harrison, N. A., and Bullmore, E. T. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Research Centre: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology |
| Journal Name: | Brain, Behavior, and Immunity |
| Publisher: | Elsevier |
| ISSN: | 0889-1591 |
| ISSN (Online): | 1090-2139 |
| Published Online: | 25 August 2021 |
| Copyright Holders: | Copyright © 2021 The Authors |
| First Published: | First published in Brain, Behavior, and Immunity 98: 299-309 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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