{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T23:27:29Z","timestamp":1792106849624,"version":"4.4.0"},"reference-count":36,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,3,12]],"date-time":"2020-03-12T00:00:00Z","timestamp":1583971200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropsychopharm Rep"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>A substantial proportion of major depressive disorder patients are treatment\u2010resistant to antidepressant therapy, who require augmentation drugs, or other treatments including electroconvulsive therapy or transcranial magnetic stimulation. Identifying treatment\u2010resistant major depressive disorder patients before the actual administration of antidepressant is, however, often difficult. Accordingly, the serum biomarker to identify treatment\u2010resistant patients will be helpful in clinical settings. This study aims to clarify the appropriate biomarkers for identification of treatment\u2010resistant major depressive disorder.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>Given that immune\u2010inflammatory processes are involved in the pathogenesis of major depressive disorder, it is possible that certain cytokine\u2010related molecules could serve as clinically useful biomarkers of treatment\u2010resistant major depressive disorder patients. In this study, we measured serum levels of tumor necrosis factor\u2010\u03b1, interleukin 6, and soluble interleukin 6 receptor after major depressive disorder patients underwent antidepressant therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The serum level of soluble interleukin 6 receptor, but not interleukin 6 or tumor necrosis factor\u2010\u03b1, was significantly higher in treatment\u2010resistant major depressive disorder patients than in remitted patients, suggesting that serum soluble interleukin 6 receptor could be a good biomarker of treatment\u2010resistant major depressive disorder. Receiver operating characteristic analysis confirmed that serum soluble interleukin\u20106 receptor level measurement was useful for identification of treatment\u2010resistant major depressive disorder patients. Multiple regression analysis using the serum levels of the aforementioned cytokines as explanatory variables and the Quick Inventory of Depressive Symptomatology\u2010Self Report score (QIDS\u2010SR<jats:sub>16<\/jats:sub>) as a target variable showed that only serum soluble interleukin\u20106 receptor level could explain the severity of major depressive disorder.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Based on these results, we recommend measurement of serum soluble interleukin\u20106 receptor level to discriminate treatment\u2010resistant major depressive disorder patients. High serum soluble interleukin\u20106 receptor level is associated with the pathogenesis of treatment\u2010resistant major depressive disorder, suggesting the involvement of the interleukin 6 trans\u2010signaling system in onset of treatment\u2010resistant major depressive disorder.<\/jats:p><\/jats:sec>","DOI":"10.1002\/npr2.12100","type":"journal-article","created":{"date-parts":[[2020,3,12]],"date-time":"2020-03-12T07:50:51Z","timestamp":1583999451000},"page":"130-137","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Serum level of soluble interleukin 6 receptor is a useful biomarker for identification of treatment\u2010resistant major depressive disorder"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5906-1121","authenticated-orcid":false,"given":"Katsuhiko","family":"Yamasaki","sequence":"first","affiliation":[{"name":"Department of Neuropsychiatry The Institute of Health and Welfare Kensho\u2010kai Medical Corporation Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9293-553X","authenticated-orcid":false,"given":"Tomonori","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"SRL Inc. 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