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

Research output: Contribution to journalArticlepeer-review

Wellcome Trust Consortium for Neuroimmunology of Mood Disorders and Alzheimer's Disease (NIMA)

Original languageEnglish
Pages (from-to)299-309
Number of pages11
JournalBrain, Behavior, and Immunity
PublishedNov 2021

Bibliographical note

Funding Information: This study was funded by an award from the Wellcome Trust (grant number: 104025/Z/14/Z) for the Neuroimmunology of Mood Disorders and Alzheimer’s Disease (NIMA) Consortium in partnership with Janssen, GlaxoSmithKline, Lundbeck and Pfizer. Additional support was provided by the National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at Cambridge (Mental Health and Cell Phenotyping Hub), the NIHR BRC at South London and Maudsley NHS Foundation Trust and King’s College London, and an NIHR Senior Investigator award (to ETB). Publisher Copyright: © 2021 Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors


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.

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