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Altered peripheral immune profiles in treatment-resistant depression: response to ketamine and prediction of treatment outcome

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dc.contributor.authorKiraly, D. D.en
dc.contributor.authorHorn, S. R.en
dc.contributor.authorVan Dam, N. T.en
dc.contributor.authorCosti, S.en
dc.contributor.authorSchwartz, J.en
dc.contributor.authorKim-Schulze, S.en
dc.contributor.authorPatel, M.en
dc.contributor.authorHodes, Georgia E.en
dc.contributor.authorRusso, Scott J.en
dc.contributor.authorMerad, Miriamen
dc.contributor.authorIosifescu, D. V.en
dc.contributor.authorCharney, D. S.en
dc.contributor.authorMurrough, J.W.en
dc.contributor.departmentSchool of Neuroscienceen
dc.coverage.spatialUnited Statesen
dc.date.accessioned2018-02-13T16:19:24Zen
dc.date.available2018-02-13T16:19:24Zen
dc.date.issued2017-03-21en
dc.description.abstractA subset of patients with depression have elevated levels of inflammatory cytokines, and some studies demonstrate interaction between inflammatory factors and treatment outcome. However, most studies focus on only a narrow subset of factors in a patient sample. In the current study, we analyzed broad immune profiles in blood from patients with treatment-resistant depression (TRD) at baseline and following treatment with the glutamate modulator ketamine. Serum was analyzed from 26 healthy control and 33 actively depressed TRD patients free of antidepressant medication, and matched for age, sex and body mass index. All subjects provided baseline blood samples, and TRD subjects had additional blood draw at 4 and 24 h following intravenous infusion of ketamine (0.5 mg kg-1). Samples underwent multiplex analysis of 41 cytokines, chemokines and growth factors using quantitative immunoassay technology. Our a priori hypothesis was that TRD patients would show elevations in canonical pro-inflammatory cytokines; analyses demonstrated significant elevation of the pro-inflammatory cytokine interleukin-6. Further exploratory analyses revealed significant regulation of four additional soluble factors in patients with TRD. Several cytokines showed transient changes in level after ketamine, but none correlated with treatment response. Low pretreatment levels of fibroblast growth factor 2 were associated with ketamine treatment response. In sum, we found that patients with TRD demonstrate a unique pattern of increased inflammatory mediators, chemokines and colony-stimulating factors, providing support for the immune hypothesis of TRD. These patterns suggest novel treatment targets for the subset of patients with TRD who evidence dysregulated immune functioning.en
dc.description.versionPublished versionen
dc.identifier.doihttps://doi.org/10.1038/tp.2017.31en
dc.identifier.eissn2158-3188en
dc.identifier.issue3en
dc.identifier.orcidHodes, GE [0000-0002-1551-2178]en
dc.identifier.urihttp://hdl.handle.net/10919/82071en
dc.identifier.volume7en
dc.languageengen
dc.relation.urihttps://www.ncbi.nlm.nih.gov/pubmed/28323284en
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectAdulten
dc.subjectCase-Control Studiesen
dc.subjectChemokinesen
dc.subjectCytokinesen
dc.subjectDepressive Disorder, Majoren
dc.subjectDepressive Disorder, Treatment-Resistanten
dc.subjectExcitatory Amino Acid Antagonistsen
dc.subjectFemaleen
dc.subjectFibroblast Growth Factor 2en
dc.subjectHumansen
dc.subjectInflammationen
dc.subjectInfusions, Intravenousen
dc.subjectIntercellular Signaling Peptides and Proteinsen
dc.subjectInterleukin-1alphaen
dc.subjectInterleukin-1betaen
dc.subjectInterleukin-6en
dc.subjectKetamineen
dc.subjectMaleen
dc.subjectMiddle Ageden
dc.subjectPrognosisen
dc.subjectTreatment Outcomeen
dc.subjectTumor Necrosis Factor-alphaen
dc.titleAltered peripheral immune profiles in treatment-resistant depression: response to ketamine and prediction of treatment outcomeen
dc.title.serialTranslational Psychiatryen
dc.typeArticle - Refereeden
dc.type.otherJournal Articleen
dc.type.otherResearch Support, Non-U.S. Gov'ten
dc.type.otherResearch Support, N.I.H., Extramuralen
dcterms.dateAccepted2017-01-24en
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/Scienceen
pubs.organisational-group/Virginia Tech/Science/COS T&R Facultyen
pubs.organisational-group/Virginia Tech/Science/School of Neuroscienceen
pubs.organisational-group/Virginia Tech/University Research Institutesen
pubs.organisational-group/Virginia Tech/University Research Institutes/Fralin Life Sciencesen
pubs.organisational-group/Virginia Tech/University Research Institutes/Fralin Life Sciences/Fralin Affiliated Facultyen

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