{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T18:03:16Z","timestamp":1793642596385,"version":"4.5.1"},"reference-count":52,"publisher":"Canadian Science Publishing","issue":"1","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.nrcresearchpress.com\/page\/about\/CorporateTextAndDataMining"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Psychiatry Neurosci"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p> Tryptophan metabolism via the kynurenine pathway is considered the link between the immune and endocrine systems. Dysregulation of serotonergic transmission can stem from the direct influence of interferon-\u03b1 on the activity of serotonergic receptors 5-HT<jats:sub>1A<\/jats:sub> and 5-HT<jats:sub>2A<\/jats:sub>, and from its indirect effect on tryptophan metabolism. Induction of the kynurenine pathway increases the concentration of neurotoxic kynurenine metabolites, and the activity of kynurenine derivatives is linked to the onset of depression. The aim of our study was to evaluate the relationships between depressive symptoms and kynurenine, tryptophan, anthranilic acid and kynurenic acid concentrations, indolamine 2,3-dioxygenase (IDO) activity and tryptophan availability to the brain. <\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p> The study followed a prospective longitudinal cohort design. We evaluated 101 patients with chronic hepatitis C who were treated with pegylated interferon-\u03b12a, and 40 controls who were awaiting treatment. We evaluated the relationships between total score on the Montgomery\u2013\u00c5sberg Depression Rating Scale and kynurenine, tryptophan, anthranilic acid and kynurenic acid concentrations, IDO activity and tryptophan availability to the brain. A logistic regression model was adapted for the diagnosis of major depressive disorder at each time point, taking into account changes in parameters of the kynurenine pathway between a given time point and the baseline measurement. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> Of the treated patients, 44% fulfilled the criteria for major depressive disorder at least once during the 24 weeks of treatment. Anthranilic acid concentrations were significantly increased compared to baseline for all time points except week 2. Tryptophan availability showed a significant decrease (\u03b2 = \u22120.09, p = 0.01) only in week 12 of treatment. Over time, kynurenine, tryptophan and anthranilic acid concentrations, as well as IDO activity and tryptophan availability to the brain, were significantly associated with total score on the Montgomery\u2013\u00c5sberg Depression Rating Scale. A logistic regression model revealed that participants with decreased tryptophan availability to the brain at 12 weeks of treatment and participants with increased anthranilic acid concentrations at week 24 of treatment were at increased risk for diagnosis of major depressive disorder (odds ratios 2.92 and 3.59, respectively). <\/jats:p><\/jats:sec><jats:sec><jats:title>Limitations<\/jats:title><jats:p> This study had an open-label design in a population receiving naturalistic treatment. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> The present study provides the first direct evidence of the role of anthranilic acid in the pathogenesis of inflammation-induced major depressive disorder during treatment for hepatitis C with pegylated interferon-\u03b12a. <\/jats:p><\/jats:sec>","DOI":"10.1503\/jpn.190139","type":"journal-article","created":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T15:45:42Z","timestamp":1614354342000},"page":"E166-E175","source":"Crossref","is-referenced-by-count":35,"title":["The role of anthranilic acid in the increase of depressive symptoms and major depressive disorder during treatment for hepatitis C with pegylated interferon-\u03b12a and oral ribavirin"],"prefix":"10.1139","volume":"46","author":[{"given":"Tomasz","family":"Pawlowski","sequence":"first","affiliation":[{"name":"From the Division of Psychotherapy and Psychosomatic Medicine, Department of Psychiatry, Wroclaw Medical University, Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dariusz","family":"Pawlak","sequence":"additional","affiliation":[{"name":"the Department of Pharmacodynamics, Medical University of Bialystok, Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malgorzata","family":"Inglot","sequence":"additional","affiliation":[{"name":"the Department of Infectious Diseases, Liver Diseases and Acquired Immune Deficiency, Wroclaw Medical University, Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malgorzata","family":"Zalewska","sequence":"additional","affiliation":[{"name":"the Department of Infectious Diseases, Liver Diseases and Acquired Immune Deficiency, Wroclaw Medical University, Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"Marciniak","sequence":"additional","affiliation":[{"name":"the Department of Drugs Form Technology, Wroclaw Medical University, Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jolanta","family":"Bugajska","sequence":"additional","affiliation":[{"name":"the Clinical Biochemistry Department, Jagiellonian University College of Medicine, Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justyna","family":"Janocha-Litwin","sequence":"additional","affiliation":[{"name":"and the Department of Infectious Diseases and Hepatology, Wroclaw Medical University, Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof","family":"Malyszczak","sequence":"additional","affiliation":[{"name":"From the Division of Psychotherapy and Psychosomatic Medicine, Department of Psychiatry, Wroclaw Medical University, Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"155","reference":[{"key":"b1-46-1-e166\/b1-46-1-e166_1","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/S0140-6736(69)91140-4","volume":"1","author":"Lapin IP","year":"1969","journal-title":"Lancet"},{"key":"b2-46-1-e166\/b2-46-1-e166_1","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1097\/00004714-200202000-00014","volume":"22","author":"Bonaccorso S","year":"2002","journal-title":"J Clin Psychopharmacol"},{"key":"b3-46-1-e166\/b3-46-1-e166_1","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.jhep.2009.10.007","volume":"52","author":"Sch\u00e4fer A","year":"2010","journal-title":"J Hepatol"},{"key":"b4-46-1-e166\/b4-46-1-e166_1","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1023\/A:1020929415443","volume":"24","author":"Abe S","year":"1999","journal-title":"Neurochem Res"},{"key":"b5-46-1-e166\/b5-46-1-e166_1","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1038\/sj.mp.4000995","volume":"7","author":"Capuron L","year":"2002","journal-title":"Mol Psychiatry"},{"key":"b6-46-1-e166\/b6-46-1-e166_1","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1038\/sj.mp.4001600","volume":"10","author":"Wichers MC","year":"2005","journal-title":"Mol Psychiatry"},{"key":"b7-46-1-e166\/b7-46-1-e166_1","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1124\/jpet.111.189860","volume":"341","author":"Banerjee J","year":"2012","journal-title":"J Pharmacol Exp Ther"},{"key":"b8-46-1-e166\/b8-46-1-e166_1","first-page":"1","volume":"5","author":"Perez-De La Cruz V","year":"2012","journal-title":"Int J Tryptophan Res"},{"key":"b9-46-1-e166\/b9-46-1-e166_1","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.pnpbp.2013.08.008","volume":"48","author":"Myint AM","year":"2014","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"b10-46-1-e166\/b10-46-1-e166_1","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1038\/nrn2297","volume":"9","author":"Dantzer R","year":"2008","journal-title":"Nat Rev Neurosci"},{"key":"b11-46-1-e166\/b11-46-1-e166_1","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/0306-9877(91)90272-Z","volume":"35","author":"Smith RS","year":"1991","journal-title":"Med Hypotheses"},{"key":"b12-46-1-e166\/b12-46-1-e166_1","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.bbi.2015.06.001","volume":"49","author":"Haapakoski R","year":"2015","journal-title":"Brain Behav Immun"},{"key":"b13-46-1-e166\/b13-46-1-e166_1","first-page":"AMP074","volume":"135","author":"Huang M","year":"2017","journal-title":"Circulation"},{"key":"b14-46-1-e166\/b14-46-1-e166_1","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.neubiorev.2018.09.006","volume":"94","author":"Dooley LN","year":"2018","journal-title":"Neurosci Biobehav Rev"},{"key":"b15-46-1-e166\/b15-46-1-e166_1","doi-asserted-by":"crossref","first-page":"430","DOI":"10.3389\/fncel.2014.00430","volume":"8","author":"Calabrese F","year":"2014","journal-title":"Front Cell Neurosci"},{"key":"b16-46-1-e166\/b16-46-1-e166_1","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/7854_2016_13","volume":"31","author":"Felger JC","year":"2017","journal-title":"Curr Top Behav Neurosci"},{"key":"b17-46-1-e166\/b17-46-1-e166_1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/B978-0-12-811073-7.00003-9","volume-title":"Inflammation and immunity in depression","author":"Nikkheslat N","year":"2018"},{"key":"b18-46-1-e166\/b18-46-1-e166_1","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.jad.2004.04.002","volume":"82","author":"Loftis JM","year":"2004","journal-title":"J Affect Disord"},{"key":"b19-46-1-e166\/b19-46-1-e166_1","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/7854_2016_40","volume":"31","author":"Haroon E","year":"2017","journal-title":"Curr Top Behav Neurosci"},{"key":"b20-46-1-e166\/b20-46-1-e166_1","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/j.pnpbp.2010.12.017","volume":"35","author":"Maes M","year":"2011","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"b21-46-1-e166\/b21-46-1-e166_1","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.phrs.2010.10.009","volume":"63","author":"Comai S","year":"2011","journal-title":"Pharmacol Res"},{"key":"b22-46-1-e166\/b22-46-1-e166_1","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1038\/mp.2009.116","volume":"15","author":"Raison CL","year":"2010","journal-title":"Mol Psychiatry"},{"key":"b23-46-1-e166\/b23-46-1-e166_1","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1038\/sj.mp.4000995","volume":"7","author":"Capuron L","year":"2002","journal-title":"Mol Psychiatry"},{"key":"b24-46-1-e166\/b24-46-1-e166_1","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.jcv.2014.03.004","volume":"60","author":"Pawlowski T","year":"2014","journal-title":"J Clin Virol"},{"key":"b25-46-1-e166\/b25-46-1-e166_1","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1186\/s12879-015-1305-1","volume":"15","author":"Jab\u0142onska J","year":"2015","journal-title":"BMC Infect Dis"},{"key":"b26-46-1-e166\/b26-46-1-e166_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.psyneuen.2018.06.004","volume":"97","author":"Pawlowski T","year":"2018","journal-title":"Psychoneuroendocrinology"},{"key":"b27-46-1-e166\/b27-46-1-e166_1","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1001\/archpsyc.1990.01810180089012","volume":"47","author":"Wing JK","year":"1990","journal-title":"Arch Gen Psychiatry"},{"key":"b28-46-1-e166\/b28-46-1-e166_1","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1192\/bjp.134.4.382","volume":"134","author":"Montgomery SA","year":"1979","journal-title":"Br J Psychiatry"},{"key":"b29-46-1-e166\/b29-46-1-e166_1","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/0003-2697(88)90478-2","volume":"172","author":"Holmes EW","year":"1988","journal-title":"Anal Biochem"},{"key":"b30-46-1-e166\/b30-46-1-e166_1","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/0378-4347(95)00341-X","volume":"675","author":"Herve C","year":"1996","journal-title":"J Chromatogr B Biomed Appl"},{"key":"b31-46-1-e166\/b31-46-1-e166_1","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1620\/tjem.153.79","volume":"153","author":"Igari T","year":"1987","journal-title":"Tohoku J Exp Med"},{"key":"b32-46-1-e166\/b32-46-1-e166_1","doi-asserted-by":"crossref","first-page":"365","DOI":"10.15761\/IMM.1000169","volume":"2","author":"Oxenkrug G","year":"2015","journal-title":"Integr Mol Med"},{"key":"b33-46-1-e166\/b33-46-1-e166_1","first-page":"1059","volume":"4","author":"Oxenkrug G","year":"2016","journal-title":"Ann Psychiatry Ment Health"},{"key":"b34-46-1-e166\/b34-46-1-e166_1","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/S0014-5793(97)00374-8","volume":"408","author":"Toma S","year":"1997","journal-title":"FEBS Lett"},{"key":"b35-46-1-e166\/b35-46-1-e166_1","doi-asserted-by":"crossref","first-page":"2007","DOI":"10.1111\/j.1471-4159.1991.tb03460.x","volume":"56","author":"Fukui S","year":"1991","journal-title":"J Neurochem"},{"key":"b36-46-1-e166\/b36-46-1-e166_1","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/7854_2016_6","volume":"31","author":"Dantzer R","year":"2017","journal-title":"Curr Top Behav Neurosci"},{"key":"b37-46-1-e166\/b37-46-1-e166_1","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1111\/j.1432-1033.1996.0460u.x","volume":"239","author":"Alberati-Giani D","year":"1996","journal-title":"Eur J Biochem"},{"key":"b38-46-1-e166\/b38-46-1-e166_1","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1111\/j.1471-4159.1990.tb04553.x","volume":"55","author":"Baran H","year":"1990","journal-title":"J Neurochem"},{"key":"b39-46-1-e166\/b39-46-1-e166_1","doi-asserted-by":"crossref","first-page":"36554","DOI":"10.1074\/jbc.M113.503813","volume":"288","author":"Giorgini F","year":"2013","journal-title":"J Biol Chem"},{"key":"b40-46-1-e166\/b40-46-1-e166_1","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/s10571-006-9124-y","volume":"27","author":"Schuck PF","year":"2007","journal-title":"Cell Mol Neurobiol"},{"key":"b41-46-1-e166\/b41-46-1-e166_1","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.schres.2017.02.025","volume":"187","author":"Shimamoto A","year":"2017","journal-title":"Schizophr Res"},{"key":"b42-46-1-e166\/b42-46-1-e166_1","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.neuroscience.2017.09.049","volume":"370","author":"Petschner P","year":"2018","journal-title":"Neuroscience"},{"key":"b43-46-1-e166\/b43-46-1-e166_1","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.jad.2017.06.001","volume":"233","author":"Kageyama Y","year":"2018","journal-title":"J Affect Disord"},{"key":"b44-46-1-e166\/b44-46-1-e166_1","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1111\/j.1440-1681.2008.05077.x","volume":"36","author":"Mackay GM","year":"2009","journal-title":"Clin Exp Pharmacol Physiol"},{"key":"b45-46-1-e166\/b45-46-1-e166_1","doi-asserted-by":"crossref","first-page":"5249","DOI":"10.1128\/IAI.73.8.5249-5251.2005","volume":"73","author":"Clark CJ","year":"2005","journal-title":"Infect Immun"},{"key":"b46-46-1-e166\/b46-46-1-e166_1","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.bbr.2016.09.050","volume":"317","author":"Tashiro T","year":"2017","journal-title":"Behav Brain Res"},{"key":"b47-46-1-e166\/b47-46-1-e166_1","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1046\/j.1471-4159.2002.00955.x","volume":"82","author":"Kita T","year":"2002","journal-title":"J Neurochem"},{"key":"b48-46-1-e166\/b48-46-1-e166_1","doi-asserted-by":"crossref","first-page":"12884","DOI":"10.1523\/JNEUROSCI.4101-07.2007","volume":"27","author":"Guillemin GJ","year":"2007","journal-title":"J Neurosci"},{"key":"b49-46-1-e166\/b49-46-1-e166_1","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1007\/s00424-005-1487-2","volume":"451","author":"Pajor AM","year":"2006","journal-title":"Pflugers Arch"},{"key":"b50-46-1-e166\/b50-46-1-e166_1","doi-asserted-by":"crossref","first-page":"51","DOI":"10.4137\/IJTR.S4282","volume":"3","author":"Darlington LG","year":"2010","journal-title":"Int J Tryptophan Res"},{"key":"b51-46-1-e166\/b51-46-1-e166_1","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.jad.2006.07.013","volume":"98","author":"Myint AM","year":"2007","journal-title":"J Affect Disord"},{"key":"b52-46-1-e166\/b52-46-1-e166_1","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.bbi.2017.10.012","volume":"69","author":"Rantala MJ","year":"2018","journal-title":"Brain Behav Immun"}],"container-title":["Journal of Psychiatry and Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdnsciencepub.com\/doi\/full-xml\/10.1503\/jpn.190139","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdnsciencepub.com\/doi\/pdf\/10.1503\/jpn.190139","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T20:00:26Z","timestamp":1757620826000},"score":1,"resource":{"primary":{"URL":"https:\/\/cdnsciencepub.com\/doi\/10.1503\/jpn.190139"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":52,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["10.1503\/jpn.190139"],"URL":"https:\/\/doi.org\/10.1503\/jpn.190139","relation":{},"ISSN":["1180-4882","1488-2434"],"issn-type":[{"value":"1180-4882","type":"print"},{"value":"1488-2434","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1]]}}}