{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:35:57Z","timestamp":1790357757459,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2014,8,11]],"date-time":"2014-08-11T00:00:00Z","timestamp":1407715200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001868","name":"National Science Council, Taiwan","doi-asserted-by":"crossref","award":["NSC98-2314-B-038-020-MY3"],"award-info":[{"award-number":["NSC98-2314-B-038-020-MY3"]}],"id":[{"id":"10.13039\/501100001868","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bipolar Disorders"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>A proinflammatory phase with various immunomodulatory mechanisms has been noted in bipolar mania and major depression. Weight gain and increased production of leptin may be associated with immunomodulation and insulin resistance in bipolar disorder. However, immunomodulation and its linkage with leptin and insulin in the depressive episode of bipolar disorder remain unclear. We investigated alterations in inflammatory markers and their relationship with leptin and insulin levels in patients with phases of bipolar disorder from acute depression to full remission.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Thirty\u2010two physically healthy bipolar I depressed patients aged &lt;45\u00a0years and age\u2010 and sex\u2010matched healthy controls participated in this study. We measured their circulating levels of leptin, insulin, high\u2010sensitivity C\u2010reactive protein (hs\u2010CRP), soluble interleukin\u20102 receptor (<jats:styled-content style=\"fixed-case\">sIL<\/jats:styled-content>\u20102R), soluble interleukin\u20106 receptor (<jats:styled-content style=\"fixed-case\">sIL<\/jats:styled-content>\u20106R), soluble tumor necrosis factor receptor 1 (<jats:styled-content style=\"fixed-case\">sTNF<\/jats:styled-content>\u2010R1), and interleukin\u20101 receptor antagonist (IL\u20101Ra) in three phases, i.e., acute depression, subsequent partial remission, and full remission.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In acute depression, subsequent partial remission, and full remission, patients with bipolar disorder had significantly higher mean levels of hs\u2010CRP, IL\u20101Ra,<jats:styled-content style=\"fixed-case\">sTNF<\/jats:styled-content>\u2010R1, and<jats:styled-content style=\"fixed-case\">sIL<\/jats:styled-content>\u20102R compared with control subjects. The IL\u20101Ra and<jats:styled-content style=\"fixed-case\">sTNF<\/jats:styled-content>\u2010R1 levels in various affective phases were significantly correlated to body mass index, leptin level, circulating lipids, and medication status. The<jats:styled-content style=\"fixed-case\">sIL<\/jats:styled-content>\u20102R levels in the three affective phases were all independent of other inflammatory markers and clinical and laboratory variables. Patients showed no alteration of<jats:styled-content style=\"fixed-case\">sIL<\/jats:styled-content>\u20106R levels through the depressive episode.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Patients with bipolar disorder in depressive episodes may exhibit persistent inflammation with elevated levels of hs\u2010CRP, IL\u20101Ra,<jats:styled-content style=\"fixed-case\">sTNF<\/jats:styled-content>\u2010R1, and<jats:styled-content style=\"fixed-case\">sIL<\/jats:styled-content>\u20102R but not<jats:styled-content style=\"fixed-case\">sIL<\/jats:styled-content>\u20106R from the acute phases to full remission. Only<jats:styled-content style=\"fixed-case\">sIL<\/jats:styled-content>\u20102R production seems to be tightly linked with the pathophysiology of bipolar depression and is independent of insulin and leptin levels.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bdi.12240","type":"journal-article","created":{"date-parts":[[2014,8,11]],"date-time":"2014-08-11T12:32:58Z","timestamp":1407760378000},"page":"800-808","source":"Crossref","is-referenced-by-count":41,"title":["Persistent inflammation and its relationship to leptin and insulin in phases of bipolar disorder from acute depression to full remission"],"prefix":"10.1111","volume":"16","author":[{"given":"Shang\u2010Ying","family":"Tsai","sequence":"first","affiliation":[{"name":"Department of Psychiatry School of Medicine College of Medicine Taipei Medical University Taipei Taiwan"},{"name":"Department of Psychiatry and Psychiatric Research Center Taipei Medical University Hospital Taipei 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