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dc.contributor.authorWittenberg, Gayle M
dc.contributor.authorGreene, Jon
dc.contributor.authorVértes, Petra E
dc.contributor.authorDrevets, Wayne C
dc.contributor.authorBullmore, Edward T
dc.date.accessioned2020-05-07T23:30:13Z
dc.date.available2020-05-07T23:30:13Z
dc.date.issued2020-10-15
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. METHODS: We searched for all case-control studies on major depressive disorder that reported microarray or RNA sequencing measurements on whole blood or peripheral blood mononuclear cells. Primary datasets were reanalyzed, 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 (N = 1754 depressed cases and N = 1145 healthy controls). Fifty-two genes were called significant by 2 of the primary studies (published overlap list). After harmonization of analysis across 8 accessible datasets (n = 1706 cases, n = 1098 controls), 272 genes were coincidentally listed in the top 3% most differentially expressed genes in 2 or more studies of whole blood or peripheral blood mononuclear cells with concordant direction of effect (harmonized overlap list). By meta-analysis of standardized mean difference across 4 studies of whole-blood samples (n = 1567 cases, n = 954 controls), 343 genes were found with false discovery rate <5% (standardized mean difference meta-analysis list). These 3 lists intersected significantly. Genes abnormally expressed in major depressive disorder were enriched for innate immune-related functions, coded for nonrandom protein-protein interaction networks, and coexpressed 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-Electronic
dc.languageeng
dc.publisherElsevier BV
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectNeutrophils
dc.subjectLeukocytes, Mononuclear
dc.subjectHumans
dc.subjectCase-Control Studies
dc.subjectGene Expression Profiling
dc.subjectDepressive Disorder, Major
dc.subjectGene Expression Regulation
dc.subjectGene Regulatory Networks
dc.subjectImmunity, Innate
dc.subjectTranscriptome
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.
dc.typeArticle
prism.endingPage637
prism.issueIdentifier8
prism.publicationDate2020
prism.publicationNameBiol Psychiatry
prism.startingPage625
prism.volume88
dc.identifier.doi10.17863/CAM.52210
dcterms.dateAccepted2020-05-03
rioxxterms.versionofrecord10.1016/j.biopsych.2020.05.006
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2020-10
dc.contributor.orcidVertes, Petra [0000-0002-0992-3210]
dc.contributor.orcidBullmore, Edward [0000-0002-8955-8283]
dc.identifier.eissn1873-2402
rioxxterms.typeJournal Article/Review
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-idMedical Research Council (MC_G0802534)
pubs.funder-project-idMedical Research Council (MR/L014815/1)
pubs.funder-project-idMQ: Transforming Mental Health (MQ17-24 Vertes)
cam.issuedOnline2020-05-13
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