Functional resting state connectivity is differentially associated with IL-6 and TNF-α in depression and in healthy controls

Abstract Inflammatory processes have been implicated in the pathophysiology of depression. In human studies, inflammation has been shown to act as a critical disease modifier, promoting susceptibility to depression and modulating specific endophenotypes of depression. However, there is scant documen...

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Main Authors: Christian N. Schmitz, Gebhard Sammer, Elena Neumann, Carlo Blecker, Gerhard Gründer, Hana Adolphi, Eva Kathrin Lamadé, Bruno Pedraz-Petrozzi
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-85514-0
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author Christian N. Schmitz
Gebhard Sammer
Elena Neumann
Carlo Blecker
Gerhard Gründer
Hana Adolphi
Eva Kathrin Lamadé
Bruno Pedraz-Petrozzi
author_facet Christian N. Schmitz
Gebhard Sammer
Elena Neumann
Carlo Blecker
Gerhard Gründer
Hana Adolphi
Eva Kathrin Lamadé
Bruno Pedraz-Petrozzi
author_sort Christian N. Schmitz
collection DOAJ
description Abstract Inflammatory processes have been implicated in the pathophysiology of depression. In human studies, inflammation has been shown to act as a critical disease modifier, promoting susceptibility to depression and modulating specific endophenotypes of depression. However, there is scant documentation of how inflammatory processes are associated with neural activity in patients with depression. We therefore tested the hypothesis that the peripheral inflammation markers IL-6 and TNF-α correlate with neural resting state network functional connectivity in depression using functional magnetic resonance imaging (fMRI) and compared it with healthy controls. We used fMRI to investigate the functional connectivity (FC) of the resting state Default Mode Network (DMN) and Salience/Ventral Attention Network (SAL) and their association with the peripheral inflammation markers IL-6 and TNF-α in 25 patients with depression and compared it to 24 healthy subjects. Results of this imaging study revealed that both DMN and SAL resting state networks are differentially associated with distinct immunological pathways depending on whether a person has a depressive phenotype or is healthy. While the DMN FC correlated with the concentration of the cytokine IL-6 in healthy subjects, SAL FC’s connectivity correlated with the cytokine TNF-α's concentration. This study highlights the importance of peripheral inflammatory processes in depression and suggests a modulatory effect on neural resting state networks depending on the state of depression.
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spelling doaj-art-c42ced6d4fbd49bb9003635b8d7a115e2025-01-19T12:22:28ZengNature PortfolioScientific Reports2045-23222025-01-0115111110.1038/s41598-025-85514-0Functional resting state connectivity is differentially associated with IL-6 and TNF-α in depression and in healthy controlsChristian N. Schmitz0Gebhard Sammer1Elena Neumann2Carlo Blecker3Gerhard Gründer4Hana Adolphi5Eva Kathrin Lamadé6Bruno Pedraz-Petrozzi7Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of HeidelbergFaculty of Psychology and Sports Science, Justus-Liebig UniversityInternal Medicine and Rheumatology, Justus-Liebig UniversityBender Institute of Neuroimaging (BION), Faculty of Psychology and Sports Science, Justus-Liebig UniversityGerman Center for Mental Health (DZPG), Partner Site MannheimGerman Center for Mental Health (DZPG), Partner Site MannheimDepartment of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of HeidelbergDepartment of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of HeidelbergAbstract Inflammatory processes have been implicated in the pathophysiology of depression. In human studies, inflammation has been shown to act as a critical disease modifier, promoting susceptibility to depression and modulating specific endophenotypes of depression. However, there is scant documentation of how inflammatory processes are associated with neural activity in patients with depression. We therefore tested the hypothesis that the peripheral inflammation markers IL-6 and TNF-α correlate with neural resting state network functional connectivity in depression using functional magnetic resonance imaging (fMRI) and compared it with healthy controls. We used fMRI to investigate the functional connectivity (FC) of the resting state Default Mode Network (DMN) and Salience/Ventral Attention Network (SAL) and their association with the peripheral inflammation markers IL-6 and TNF-α in 25 patients with depression and compared it to 24 healthy subjects. Results of this imaging study revealed that both DMN and SAL resting state networks are differentially associated with distinct immunological pathways depending on whether a person has a depressive phenotype or is healthy. While the DMN FC correlated with the concentration of the cytokine IL-6 in healthy subjects, SAL FC’s connectivity correlated with the cytokine TNF-α's concentration. This study highlights the importance of peripheral inflammatory processes in depression and suggests a modulatory effect on neural resting state networks depending on the state of depression.https://doi.org/10.1038/s41598-025-85514-0
spellingShingle Christian N. Schmitz
Gebhard Sammer
Elena Neumann
Carlo Blecker
Gerhard Gründer
Hana Adolphi
Eva Kathrin Lamadé
Bruno Pedraz-Petrozzi
Functional resting state connectivity is differentially associated with IL-6 and TNF-α in depression and in healthy controls
Scientific Reports
title Functional resting state connectivity is differentially associated with IL-6 and TNF-α in depression and in healthy controls
title_full Functional resting state connectivity is differentially associated with IL-6 and TNF-α in depression and in healthy controls
title_fullStr Functional resting state connectivity is differentially associated with IL-6 and TNF-α in depression and in healthy controls
title_full_unstemmed Functional resting state connectivity is differentially associated with IL-6 and TNF-α in depression and in healthy controls
title_short Functional resting state connectivity is differentially associated with IL-6 and TNF-α in depression and in healthy controls
title_sort functional resting state connectivity is differentially associated with il 6 and tnf α in depression and in healthy controls
url https://doi.org/10.1038/s41598-025-85514-0
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