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dc.contributor.authorLeday, Gwenaelen
dc.contributor.authorVertes, Petraen
dc.contributor.authorRichardson, Sen
dc.contributor.authorGreene, JRen
dc.contributor.authorRegan, Ten
dc.contributor.authorKhan, Sen
dc.contributor.authorHenderson, Ren
dc.contributor.authorFreeman, TCen
dc.contributor.authorPariante, CMen
dc.contributor.authorHarrison, NAen
dc.contributor.authorMRC Immunopsychiatry Consortium,en
dc.contributor.authorPerry, VHen
dc.contributor.authorDrevets, WCen
dc.contributor.authorWittenberg, GMen
dc.contributor.authorBullmore, Edwarden
dc.date.accessioned2017-07-27T11:57:59Z
dc.date.available2017-07-27T11:57:59Z
dc.date.issued2017-07-06en
dc.identifier.issn0006-3223
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/265752
dc.description.abstractBACKGROUND: Peripheral inflammation is often associated with major depressive disorder (MDD), and immunological biomarkers of depression remain a focus of investigation. METHODS: We used microarray data on whole blood from two independent case-control studies of MDD: the GlaxoSmithKline-High-Throughput Disease-specific target Identification Program [GSK-HiTDiP] study (113 patients and 57 healthy control subjects) and the Janssen-Brain Resource Company study (94 patients and 100 control subjects). Genome-wide differential gene expression analysis (18,863 probes) resulted in a p value for each gene in each study. A Bayesian method identified the largest p-value threshold (q = .025) associated with twice the number of genes differentially expressed in both studies compared with the number of coincidental case-control differences expected by chance. RESULTS: A total of 165 genes were differentially expressed in both studies with concordant direction of fold change. The 90 genes overexpressed (or UP genes) in MDD were significantly enriched for immune response to infection, were concentrated in a module of the gene coexpression network associated with innate immunity, and included clusters of genes with correlated expression in monocytes, monocyte-derived dendritic cells, and neutrophils. In contrast, the 75 genes underexpressed (or DOWN genes) in MDD were associated with the adaptive immune response and included clusters of genes with correlated expression in T cells, natural killer cells, and erythroblasts. Consistently, the MDD patients with overexpression of UP genes also had underexpression of DOWN genes (correlation > .70 in both studies). CONCLUSIONS: MDD was replicably associated with proinflammatory activation of the peripheral innate immune system, coupled with relative inactivation of the adaptive immune system, indicating the potential of transcriptional biomarkers for immunological stratification of patients with depression.
dc.languageengen
dc.language.isoenen
dc.publisherElsevier
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectAffymetrixen
dc.subjectBayesianen
dc.subjectBiomarkeren
dc.subjectInflammationen
dc.subjectSystemsen
dc.subjectTranscriptomeen
dc.titleReplicable and Coupled Changes in Innate and Adaptive Immune Gene Expression in Two Case-Control Studies of Blood Microarrays in Major Depressive Disorderen
dc.typeArticle
prism.publicationDate2017en
prism.publicationNameBiological Psychiatryen
dc.identifier.doi10.17863/CAM.11587
dcterms.dateAccepted2017-01-12en
rioxxterms.versionofrecord10.1016/j.biopsych.2017.01.021en
rioxxterms.versionVoRen
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2017-07-06en
dc.contributor.orcidLeday, Gwenael [0000-0002-3753-4060]
dc.contributor.orcidVertes, Petra [0000-0002-0992-3210]
dc.contributor.orcidBullmore, Edward [0000-0002-8955-8283]
dc.identifier.eissn1873-2402
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MR/L014815/1)
pubs.funder-project-idMRC (MR/K020706/1)


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