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Systemic inflammation also perturbs brain function and microstructure, though how these are related remains unclear. We recruited\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u200946 healthy controls, and\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u200983 depressed cases stratified by CRP (&gt;\u00a03\u2009mg\/L:\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u200933; &lt; 3\u2009mg\/L:\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u200950). 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\u2009=\u20095%). We found that CRP was significantly associated with PD in precuneus, posterior cingulate cortex (pC\/pCC) and medial prefrontal cortex (mPFC); and with\u00a0functional 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\u2014a plausible marker of extracellular oedema\u2014and 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.\n                  <\/jats:p>","DOI":"10.1038\/s41380-021-01272-1","type":"journal-article","created":{"date-parts":[[2021,9,17]],"date-time":"2021-09-17T10:03:45Z","timestamp":1631873025000},"page":"7346-7354","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":87,"title":["Peripheral inflammation is associated with micro-structural and functional connectivity changes in depression-related brain networks"],"prefix":"10.1038","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4494-0753","authenticated-orcid":false,"given":"Manfred G.","family":"Kitzbichler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athina R.","family":"Aruldass","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5214-7421","authenticated-orcid":false,"given":"Gareth J.","family":"Barker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7640-5520","authenticated-orcid":false,"given":"Tobias C.","family":"Wood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas G.","family":"Dowell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3965-9649","authenticated-orcid":false,"given":"Samuel A.","family":"Hurley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"McLean","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Correia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Clarke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Pointon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0640-8050","authenticated-orcid":false,"given":"Jonathan","family":"Cavanagh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5518-6138","authenticated-orcid":false,"given":"Phil","family":"Cowen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9132-5091","authenticated-orcid":false,"given":"Carmine","family":"Pariante","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4550-2456","authenticated-orcid":false,"given":"Mara","family":"Cercignani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Neuroimmunology of Mood Disorders and Alzheimer\u2019s Disease (NIMA) Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward T.","family":"Bullmore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9584-3769","authenticated-orcid":false,"given":"Neil A.","family":"Harrison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,17]]},"reference":[{"key":"1272_CR1","first-page":"280","volume":"137","author":"G Krueger","year":"2001","unstructured":"Krueger G, Koo J, Lebwohl M, Menter A, Stern RS, Rolstad T. 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