{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:44:03Z","timestamp":1790739843861,"version":"4.1.0"},"reference-count":30,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2015,4,8]],"date-time":"2015-04-08T00:00:00Z","timestamp":1428451200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Although antidepressants are generally effective in the treatment of major depressive disorder (MDD), it can still take weeks before patients feel the full antidepressant effects. Despite the efficacy of standard treatments, approximately two-thirds of patients with MDD fail to respond to pharmacotherapy. Therefore, the identification of blood biomarkers that can predict the treatment response to antidepressants would be highly useful in order to improve this situation. This article discusses inflammatory molecules  as predictive biomarkers for antidepressant responses to several classes of antidepressants, including the N-methyl-d-aspartate (NMDA) receptor antagonist ketamine.<\/jats:p>","DOI":"10.3390\/ijms16047796","type":"journal-article","created":{"date-parts":[[2015,4,8]],"date-time":"2015-04-08T11:23:46Z","timestamp":1428492226000},"page":"7796-7801","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":124,"title":["Inflammatory Biomarkers as Differential Predictors of Antidepressant Response"],"prefix":"10.3390","volume":"16","author":[{"given":"Kenji","family":"Hashimoto","sequence":"first","affiliation":[{"name":"Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health,  1-8-1 Inohana, Chiba 260-7680, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,4,8]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (WHO) Depression. Fact sheet No. 369\/October 2012. Available online: http:\/\/www.who.int\/mediacentre\/factsheets\/fs369\/en\/index.html."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1007\/s11920-010-0160-4","article-title":"Biomarkers to predict antidepressant response","volume":"12","author":"Leuchter","year":"2010","journal-title":"Curr. Psychiatry Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1007\/s00406-009-0093-2","article-title":"The role of proteomics in depression research","volume":"260","author":"Harris","year":"2010","journal-title":"Eur. Arch. Psychiatry Clin. Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.drudis.2014.02.002","article-title":"Are there meaningful biomarkers of treatment response for depression","volume":"19","author":"Breitenstein","year":"2014","journal-title":"Drug Discov. Today"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.brainresrev.2009.05.005","article-title":"Emerging role of glutamate in the pathophysiology of major depressive disorder","volume":"61","author":"Hashimoto","year":"2009","journal-title":"Brain Res. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1016\/j.biopsych.2008.11.029","article-title":"Inflammation and its discontents: The role of cytokines in the pathophysiology of major depression","volume":"65","author":"Miller","year":"2009","journal-title":"Biol. Psychiatry"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1001\/archgenpsychiatry.2010.161","article-title":"Inflammation, sanitation, and consternation: Loss of contact with coevolved, tolerogenic microorganisms and the pathophysiology and treatment of major depression","volume":"67","author":"Raison","year":"2010","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1038\/nrn2297","article-title":"From inflammation to sickness and depression: When the immune system subjugates the brain","volume":"9","author":"Dantzer","year":"2008","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/sj.mp.4002148","article-title":"Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice","volume":"14","author":"Lawson","year":"2009","journal-title":"Mol. Psychiatry"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"31","DOI":"10.9758\/cpn.2014.12.1.31","article-title":"Effects of brilliant blue G on serum tumor necrosis factor-\u03b1 levels and depression-like behavior in mice after lipopolysaccharide administration","volume":"12","author":"Ma","year":"2014","journal-title":"Clin. Psychopharmacol. Neurosci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/ijnp\/pyu077","article-title":"Antidepressant effects of TrkB ligands on depression-like behavior and dendritic changes in mice after inflammation","volume":"18","author":"Zhang","year":"2015","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1016\/j.pbb.2012.12.003","article-title":"Effects of antidepressants on alternations in serum cytokines and depressive-like behavior in mice after lipopolysaccharide administration","volume":"103","author":"Ohgi","year":"2013","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.biopsych.2009.09.033","article-title":"A meta-analysis of cytokines in major depression","volume":"67","author":"Dowlati","year":"2010","journal-title":"Biol. Psychiatry"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1038\/mp.2010.52","article-title":"Altered expression of genes involved in inflammation and apoptosis in frontal cortex in major depression","volume":"16","author":"Shelton","year":"2011","journal-title":"Mol. Psychiatry"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1097\/PSY.0b013e3181907c1b","article-title":"Associations of depression with C-reactive protein, IL-1, and IL-6: A meta-analysis","volume":"71","author":"Howren","year":"2009","journal-title":"Psychosom. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1016\/j.jad.2013.06.004","article-title":"CRP, IL-6 and depression: A systematic review and meta-analysis of longitudinal studies","volume":"150","author":"Valkanova","year":"2013","journal-title":"J. Affect. Disord."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1176\/appi.ajp.2014.14010094","article-title":"An inflammatory biomarker as a differential predictor of outcome of depression treatment with escitalopram and nortriptyline","volume":"171","author":"Uher","year":"2014","journal-title":"Am. J. Psychiatry"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"97","DOI":"10.2174\/157015912800604542","article-title":"Immunomodulation mechanism of antidepressants: Interactions between serotonin\/norepinephrine balance and Th1\/Th2 balance","volume":"10","author":"Martino","year":"2012","journal-title":"Curr. Neuropharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1586\/ern.10.176","article-title":"Role of the mTOR signaling pathway in the rapid antidepressant action of ketamine","volume":"11","author":"Hashimoto","year":"2011","journal-title":"Expert Rev. Neurother."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.biopsych.2012.05.003","article-title":"Ketamine for depression: Where do we go from here","volume":"72","author":"Zarate","year":"2012","journal-title":"Biol. Psychiatry"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1016\/j.biopsych.2013.03.026","article-title":"Rapid-acting glutamtergic antidepressants: The path to ketamine and beyond","volume":"73","author":"Krystal","year":"2013","journal-title":"Biol. Psychiatry"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1016\/j.biopsych.2012.11.031","article-title":"Human biomarkers of rapid antidepressant effects","volume":"73","author":"Zarate","year":"2013","journal-title":"Biol. Psychiatry"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1007\/s00406-013-0399-y","article-title":"Glutamate modulators as potential therapeutic drugs in schizophrenia and affective disorders","volume":"263","author":"Hashimoto","year":"2013","journal-title":"Eur. Arch. Psychiatry Clin. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"72","DOI":"10.9758\/cpn.2014.12.1.72","article-title":"The R-stereoisomer of ketamine as an alternative for ketamine for treatment-resistant major depression","volume":"12","author":"Hashimoto","year":"2014","journal-title":"Clin. Psychopharmacol. Neurosci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1007\/s00213-014-3543-0","article-title":"Rapid antidepressant effects and abuse liability of ketamine","volume":"231","author":"Yang","year":"2014","journal-title":"Psychopharmacology (Berl.)"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1037\/a0038550","article-title":"A brief history of the development of antidepressant drugs: From monoamines to glutamate","volume":"23","author":"Hillhouse","year":"2015","journal-title":"Exp. Clin. Psychopharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"De Wilde, K.E., Levitch, C.F., Murrough, J.W., Mathew, S.J., and Iosifescu, D.V. (2015). The promise of ketamine for treatment-resistant depression: Current evidence and future directions. Ann. N. Y. Acad. Sci.","DOI":"10.1111\/nyas.12646"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Abdallah, C.G., Averill, L.A., and Krystal, J.H. (2015). Ketamine as a promising prototype for a new generation of rapid-acting antidepressants. Ann. N. Y. Acad. Sci.","DOI":"10.1111\/nyas.12718"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4081","DOI":"10.1007\/s00213-014-3735-7","article-title":"Blood D-serine levels as a predictive biomarker for the rapid antidepressant effects of the NMDA receptor antagonist ketamine","volume":"231","author":"Hashimoto","year":"2014","journal-title":"Psychopharmacology (Berl.)"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e19","DOI":"10.1016\/j.biopsych.2014.06.021","article-title":"Serum interleukin-6 is a predictive biomarker for ketamine\u2019s antidepressant effect in treatment-resistant patients with major depression","volume":"77","author":"Yang","year":"2015","journal-title":"Biol. Psychiatry"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/16\/4\/7796\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:44:24Z","timestamp":1760215464000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/16\/4\/7796"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,4,8]]},"references-count":30,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2015,4]]}},"alternative-id":["ijms16047796"],"URL":"https:\/\/doi.org\/10.3390\/ijms16047796","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,4,8]]}}}