Peripheral inflammation is associated with micro-structural and functional connectivity changes in depression-related brain networks

Kitzbichler, M. G. et al. (2021) Peripheral inflammation is associated with micro-structural and functional connectivity changes in depression-related brain networks. Molecular Psychiatry, 26(12), pp. 7346-7354. (doi: 10.1038/s41380-021-01272-1) (PMID:34535766) (PMCID:PMC8872995)

Abstract

Inflammation is associated with depressive symptoms and innate immune mechanisms are likely causal in some cases of major depression. Systemic inflammation also perturbs brain function and microstructure, though how these are related remains unclear. We recruited N = 46 healthy controls, and N = 83 depressed cases stratified by CRP (> 3 mg/L: N = 33; < 3 mg/L: N = 50). All completed clinical assessment, venous blood sampling for C-reactive protein (CRP) assay, and brain magnetic resonance imaging (MRI). Micro-structural MRI parameters including proton density (PD), a measure of tissue water content, were measured at 360 cortical and 16 subcortical regions. Resting-state fMRI time series were correlated to estimate functional connectivity between individual regions, as well as the sum of connectivity (weighted degree) of each region. Multiple tests for regional analysis were controlled by the false discovery rate (FDR = 5%). We found that CRP was significantly associated with PD in precuneus, posterior cingulate cortex (pC/pCC) and medial prefrontal cortex (mPFC); and with functional connectivity between pC/pCC, mPFC and hippocampus. Depression was associated with reduced weighted degree of pC/pCC, mPFC, and other nodes of the default mode network (DMN). Thus CRP-related increases in proton density—a plausible marker of extracellular oedema—and changes in functional connectivity were anatomically co-localised with DMN nodes that also demonstrated significantly reduced hubness in depression. We suggest that effects of peripheral inflammation on DMN node micro-structure and connectivity may mediate inflammatory effects on depression.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Cavanagh, Professor Jonathan and Mclean, Dr John
• Authors: Kitzbichler, M. G., Aruldass, A. R., Barker, G. J., Wood, T. C., Dowell, N. G., Hurley, S. A., McLean, J., Correia, M., Clarke, C., Pointon, L., Cavanagh, J., Cowen, P., Pariante, C., Cercignani, M., Bullmore, E. T., and Harrison, N. A.
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Mental Health and Wellbeing; 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: Molecular Psychiatry
• Publisher: Springer Nature
• ISSN: 1359-4184
• ISSN (Online): 1476-5578
• Published Online: 17 September 2021
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published in Molecular Psychiatry 26(12): 7346-7354
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
308675		Consortium of Neuroimmunology of Mood Disorders and Alzheimer's Disease	Jonathan Cavanagh	Wellcome Trust (WELLCOTR)	104025	III - Immunology