{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T23:41:26Z","timestamp":1784331686176,"version":"3.55.0"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,8,30]],"date-time":"2019-08-30T00:00:00Z","timestamp":1567123200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005205","name":"Janssen Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005205","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Bipolar Disorders"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Cytokines are thought to contribute to the pathogenesis of psychiatric symptoms by kynurenine pathway activation. Kynurenine metabolites affect neurotransmission and can cause neurotoxicity. We measured inflammatory markers in patients with bipolar disorder (BD) and studied their relation to kynurenine metabolites and mood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients with BD suffering from an acute mood episode were assigned to the depressive (n\u00a0=\u00a035) or (hypo)manic (n\u00a0=\u00a032) subgroup. Plasma levels of inflammatory markers [cytokines, C\u2010reactive protein] and kynurenine metabolites [tryptophan (TRP), kynurenine (KYN), 3\u2010hydroxykynurenine (3\u2010HK), quinolinic acid (QA), kynurenic acid (KYNA)] were measured on 6 time points during 8\u00a0months follow\u2010up. Biological marker levels in patients were compared to controls (n\u00a0=\u00a035) and correlated to scores on mood scales. Spearman correlations and linear mixed models were used for statistical analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty patients of the manic subgroup, 29 of the depressive subgroup, and 30 controls completed the study. The manic subgroup had a rapid remission of mood symptoms, but in the depressive subgroup subsyndromal symptoms persisted. No differences in inflammation were found between groups. A strong correlation between tumor necrosis factor\u2010<jats:italic>\u03b1<\/jats:italic> and KYN, KYN\/TRP, 3\u2010HK and QA (<jats:italic>\u03c1<\/jats:italic>\u00a0&gt;\u00a00.60) was specific for the manic group, but only at baseline (during mania). The depressive subgroup had a lower neuroprotective ratio (KYNA\/3\u2010HK, <jats:italic>P<\/jats:italic>\u00a0=\u00a0.0004) and a strong association between interferon\u2010y and kynurenine pathway activation (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.0001). KYNA was low in both patient groups versus controls throughout the whole follow\u2010up (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.0008).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Mania and chronic depressive symptoms in BD are accompanied by a strong interaction between inflammation and a potentially neurotoxic kynurenine metabolism.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bdi.12814","type":"journal-article","created":{"date-parts":[[2019,8,9]],"date-time":"2019-08-09T17:38:30Z","timestamp":1565372310000},"page":"59-69","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["A mood state\u2010specific interaction between kynurenine metabolism and inflammation is present in bipolar disorder"],"prefix":"10.1111","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2642-5774","authenticated-orcid":false,"given":"Seline","family":"van den Ameele","sequence":"first","affiliation":[{"name":"Collaborative Antwerp Psychiatric Research Institute (CAPRI), Faculty of Medicine and Health Sciences University of Antwerp Antwerp Belgium"},{"name":"Scientific Institute for Neuropsychiatric and Psychopharmacological Studies (SINAPS), University Psychiatric Hospital Duffel \u2010 VZW Emma\u00fcs Duffel Belgium"},{"name":"Department of Psychiatry CHU Brugmann Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander LN","family":"van Nuijs","sequence":"additional","affiliation":[{"name":"Toxicological Centre, Department of Pharmaceutical Sciences University of Antwerp Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Foon Yin","family":"Lai","sequence":"additional","affiliation":[{"name":"Toxicological Centre, Department of Pharmaceutical Sciences University of Antwerp Antwerp Belgium"},{"name":"Department of Aquatic Sciences and Assessment Swedish University of Agricultural Sciences (SLU) Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen","family":"Schuermans","sequence":"additional","affiliation":[{"name":"Collaborative Antwerp Psychiatric Research Institute (CAPRI), Faculty of Medicine and Health Sciences University of Antwerp Antwerp Belgium"},{"name":"Scientific Institute for Neuropsychiatric and Psychopharmacological Studies (SINAPS), University Psychiatric Hospital Duffel \u2010 VZW Emma\u00fcs Duffel Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Verkerk","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Biochemistry University of Antwerp Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"van Diermen","sequence":"additional","affiliation":[{"name":"Collaborative Antwerp Psychiatric Research Institute (CAPRI), Faculty of Medicine and Health Sciences University of Antwerp Antwerp Belgium"},{"name":"Scientific Institute for Neuropsychiatric and Psychopharmacological Studies (SINAPS), University Psychiatric Hospital Duffel \u2010 VZW Emma\u00fcs Duffel Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Violette","family":"Coppens","sequence":"additional","affiliation":[{"name":"Collaborative Antwerp Psychiatric Research Institute (CAPRI), Faculty of Medicine and Health Sciences University of Antwerp Antwerp Belgium"},{"name":"Scientific Institute for Neuropsychiatric and Psychopharmacological Studies (SINAPS), University Psychiatric Hospital Duffel \u2010 VZW Emma\u00fcs Duffel Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Fransen","sequence":"additional","affiliation":[{"name":"StatUa Centre for Statistics University of Antwerp Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"de Boer","sequence":"additional","affiliation":[{"name":"Janssen Research and Development A Division of Janssen Pharmaceutica N.V. Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten","family":"Timmers","sequence":"additional","affiliation":[{"name":"Janssen Research and Development A Division of Janssen Pharmaceutica N.V. Beerse Belgium"},{"name":"Reference Center for Biological Markers of Dementia (BIODEM), Institute Born\u2010Bunge University of Antwerp Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Sabbe","sequence":"additional","affiliation":[{"name":"Collaborative Antwerp Psychiatric Research Institute (CAPRI), Faculty of Medicine and Health Sciences University of Antwerp Antwerp Belgium"},{"name":"Scientific Institute for Neuropsychiatric and Psychopharmacological Studies (SINAPS), University Psychiatric Hospital Duffel \u2010 VZW Emma\u00fcs Duffel Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Morrens","sequence":"additional","affiliation":[{"name":"Collaborative Antwerp Psychiatric Research Institute (CAPRI), Faculty of Medicine and Health Sciences University of Antwerp Antwerp Belgium"},{"name":"Scientific Institute for Neuropsychiatric and Psychopharmacological Studies (SINAPS), University Psychiatric Hospital Duffel \u2010 VZW Emma\u00fcs Duffel Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,8,30]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2013.08.008"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3257"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1515\/bchm3.1989.370.2.1063"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2010.09.012"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161211795049552"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2015.02.011"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1503\/jpn.150226"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2016.05.020"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3223(01)01078-2"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2013.08.008"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2011.05.005"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-018-0038-4"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/bdi.12009"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2013.11"},{"key":"e_1_2_10_16_1","article-title":"A genome\u2010wide association study of kynurenic acid in cerebrospinal fluid: implications for psychosis and cognitive impairment in bipolar disorder","author":"Sellgren CM","year":"2015","journal-title":"Mol Psychiatry"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-019-0378-9"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2006.12.008"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2017.88"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2014.11.015"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0172699"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00406-016-0731-4"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2018.05.031"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2012.06.010"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2016.06.016"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2012.08.008"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4002148"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4000995"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4001600"},{"issue":"2","key":"e_1_2_10_30_1","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1503\/jpn.140126","article-title":"Increased levels of IL\u20106 in the cerebrospinal fluid of patients with chronic schizophrenia\u2013significance for activation of the kynurenine pathway","volume":"40","author":"Schwieler L","year":"2015","journal-title":"J Psychiatr Neurosci"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2014.03.013"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2004.02.001"},{"issue":"20","key":"e_1_2_10_33_1","first-page":"22","article-title":"The Mini\u2010International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM\u2010IV and ICD\u201010","volume":"59","author":"Sheehan DV","year":"1998","journal-title":"J Clin Psychiatr"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2044-8341.1959.tb00467.x"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.133.5.429"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2013.04.028"},{"key":"e_1_2_10_37_1","doi-asserted-by":"crossref","volume-title":"Guide to assessment scales in bipolar disorder.","author":"Vieta E","DOI":"10.1007\/978-1-907673-26-9"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/13.2.261"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2018.00250"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2015.02.007"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1089\/jir.1997.17.589"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/bdi.12291"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2010.10.001"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2017.04.015"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1097\/YCO.0b013e32835aa4b4"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/da.22084"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1991.tb03460.x"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2011.12.049"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/7854_2016_12"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2014.01.013"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2014.00098"}],"container-title":["Bipolar Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bdi.12814","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bdi.12814","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bdi.12814","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T20:57:16Z","timestamp":1694033836000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bdi.12814"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,30]]},"references-count":50,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,2]]}},"alternative-id":["10.1111\/bdi.12814"],"URL":"https:\/\/doi.org\/10.1111\/bdi.12814","archive":["Portico"],"relation":{},"ISSN":["1398-5647","1399-5618"],"issn-type":[{"value":"1398-5647","type":"print"},{"value":"1399-5618","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,30]]},"assertion":[{"value":"2019-08-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}