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dc.contributor.authorWittenberg, Gayle Men
dc.contributor.authorGreene, Jonen
dc.contributor.authorVertes, Petraen
dc.contributor.authorDrevets, Wayne Cen
dc.contributor.authorBullmore, Edwarden
dc.date.accessioned2020-05-07T23:30:13Z
dc.date.available2020-05-07T23:30:13Z
dc.date.issued2020-10en
dc.identifier.issn0006-3223
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/305128
dc.description.abstractBackground: Whole genome transcription has been measured in peripheral blood samples as a candidate biomarker of inflammation associated with major depressive disorder (MDD). Methods: We searched for all MDD case-control studies that reported microarray or RNAseq measurements on whole blood or peripheral blood mononuclear cells (PBMCs). Primary datasets were re-analysed, when openly accessible, to estimate case-control differences, and to evaluate the functional roles of differentially expressed gene lists, by technically harmonized methods. Results: We found 10 eligible studies, comprising N=1,754 depressed cases and N=1,145 healthy controls. 52 genes were called significant by two of the primary studies (published overlap list). After harmonization of analysis across 8 accessible datasets (N=1,706 cases, 1,098 controls), 272 genes were coincidentally listed in the top 3% most differentially expressed genes in two or more studies of whole blood or PBMCs with concordant direction-of-effect (harmonized overlap list). By meta-analysis of standardized mean difference (SMD) across 4 studies of whole blood samples (N=1,567 cases, 954 controls), 343 genes were found with false discovery rate < 5% (SMD meta-analysis list). These 3 lists intersected significantly. Genes abnormally expressed in MDD were enriched for innate immune related functions, coded for non-random protein-protein interaction networks, and co-expressed in the normative transcriptome module specialized for innate immune and neutrophil functions. Conclusions: Quantitative review of existing case-control data provided robust evidence for abnormal expression of gene networks important for the regulation and implementation of innate immune response. Further development of white blood cell transcriptional biomarkers for inflamed depression seems warranted.
dc.description.sponsorshipNIHR
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.publisherElsevier
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectNeutrophilsen
dc.subjectLeukocytes, Mononuclearen
dc.subjectHumansen
dc.subjectCase-Control Studiesen
dc.subjectGene Expression Profilingen
dc.subjectDepressive Disorder, Majoren
dc.subjectGene Expression Regulationen
dc.subjectGene Regulatory Networksen
dc.subjectImmunity, Innateen
dc.subjectTranscriptomeen
dc.titleMajor Depressive Disorder Is Associated With Differential Expression of Innate Immune and Neutrophil-Related Gene Networks in Peripheral Blood: A Quantitative Review of Whole-Genome Transcriptional Data From Case-Control Studies.en
dc.typeArticle
prism.endingPage637
prism.issueIdentifier8en
prism.publicationDate2020en
prism.publicationNameBiological psychiatryen
prism.startingPage625
prism.volume88en
dc.identifier.doi10.17863/CAM.52210
dcterms.dateAccepted2020-05-03en
rioxxterms.versionofrecord10.1016/j.biopsych.2020.05.006en
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2020-10en
dc.contributor.orcidVértes, Petra [0000-0002-0992-3210]
dc.contributor.orcidBullmore, Edward [0000-0002-8955-8283]
dc.identifier.eissn1873-2402
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (146281)
pubs.funder-project-idDepartment of Health (via National Institute for Health Research (NIHR)) (156239)
pubs.funder-project-idMRC (MC_G0802534)
pubs.funder-project-idMRC (MR/L014815/1)
pubs.funder-project-idMQ: Transforming Mental Health (MQ17-24 Vertes)
cam.orpheus.successTue May 26 08:16:44 BST 2020 - Embargo updated*
cam.orpheus.counter2*
rioxxterms.freetoread.startdate2021-05-31


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Attribution-NonCommercial-NoDerivatives 4.0 International
Except where otherwise noted, this item's licence is described as Attribution-NonCommercial-NoDerivatives 4.0 International