Effects of tryptophan metabolites on IFN-induced depressive symptoms

2013 Fiscal Year Final Research Report

• Project/Area Number: 24790552
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Laboratory medicine
• Research Institution: Kyoto University
• Principal Investigator: MURAKAMI Yuki 京都大学, 医学(系)研究科(研究院), 研究員 (50580106)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: トリプトファン代謝 / 副作用 / 薬物誘発性抑うつ / 発症予測

Research Abstract

The therapy for chronic hepatitis C (HCV) using interferon is currently recommended, however, psychiatric disorders such as depression are frequent in HCV patients during the therapy. Many researchers propose indoleamine 2,3-dioxygenase (IDO) 1, which is one of first rate-limiting enzyme of the kynurenine pathway, and IDO1-mediated tryptophan (TRP) metabolites be implicated in the development of IFN-induced depression. In this study, we measured TRP and its metabolites and investigated correlations between TRP metabolites and depression induced by IFN therapy. Following IFN therapy, the concentration of serum TRP was reduced, while some TRP metabolites were increased, then returned to baseline values after the end of the therapy. The ratio of TRP and metabolites were significantly increased under the therapy, especially with depression. We speculate that the indexing, combination between some TRP metabolites, is effective in prediction of the depression induced by IFN therapy.

Research Products

• [Journal Article] Indoleamine 2,3-dioxygenase 1 modulates the immuneresponse; the new therapeutic targets of this drug (2013)
  • Author(s): Yamamoto Y, Murakami Y, Hoshi M, Saito K
  • Journal Title: Nihon Yakurigaku Zasshi Volume: 142(2) Pages: 85-8
  • Peer Reviewed
• [Journal Article] Species and cell types difference in tryptophan metabolism (2013)
  • Author(s): Murakami Y, Saito K
  • Journal Title: Int J Tryptophan Res Volume: 1 Pages: 47-54
  • Peer Reviewed
• [Journal Article] Remarkable role of indoleamine 2,3-dioxygenase and tryptophan metabolites in infectious disease : potential role in macrophage-mediated inflammatory diseases (2013)
  • Author(s): Murakami Y, Hoshi M, Imamura Y, Arioka Y, Yamamoto Y, Saito K
  • Journal Title: Mediators Inflamm Volume: 2013 Pages: 1-9
  • Peer Reviewed
• [Journal Article] Matrix metalloproteinase-9 triggers the gap junction impairment and somatosensory neuronal dysfunction in septic encephalopathy (2013)
  • Author(s): Wang H, Imamura Y, Matsumoto N, Yoshikawa N, Nakagawa J, Yamakawa K, Yamada T, Murakami Y, Mitani S, Jin T, Ogura H,Shimazu T, Seiyama A
  • Journal Title: Biochem Parmacol Volume: 2(1) Pages: 1-7
  • Peer Reviewed
• [Journal Article] Studies on Tissue and Cellular Distribution of Indoleamine 2,3-Dioxygenase 2 : The Absence of IDO1 Upregulates IDO2 Expression in the Epididymis (2012)
  • Author(s): Fukunaga M, Yamamoto Y, Kawasoe M, Arioka Y, Murakami Y, Hoshi M, Saito K
  • Journal Title: J Histochem Cytochem Volume: 60(11) Pages: 854-60
  • Peer Reviewed
• [Journal Article] Regulation of Systemic Inflammation in Sepsis (2012)
  • Author(s): Imamura Y, Yoshikawa N, Murakami Y, Mitani S, Seiyama A. Inflammation and Brain
  • Journal Title: Biochem & Pharmacol Volume: 1 Pages: 127
  • Peer Reviewed
• [Journal Article] Tortella FC.Brain oxygen tension monitoring following penetrating ballistic-like brain injury in rats (2012)
  • Author(s): Murakami Y, Wei G, Yang X, Lu XC, Leung LY, Shear DA
  • Journal Title: J Neurosci Methods Volume: 203(1) Pages: 115-21
  • Peer Reviewed
• [Journal Article] Inhibition of increased indoleamine 2,3-dioxygenase activity attenuates Toxoplasma gondii replication in the lung during acute infection (2012)
  • Author(s): Murakami Y, Hoshi M, Hara A, Takemura M, Arioka Y, Yamamoto Y, Matsunami H, Funato T, Seishima M, Saito K
  • Journal Title: Cytokine Volume: 59(2) Pages: 245-51
  • Peer Reviewed
• [Presentation] 先制医療の実現に向けたコホート研究・バイオマーカー研究の推進」に関する一報 (2014)
  • Author(s): 三谷智子、松波英寿、林慎、竹村正男、村上由希、今村行雄、松岡彩加、山本梨絵、山田南実、加奈山憲代、山本康子、松尾雄志、斉藤邦明
  • Organizer: 日本疫学会第24回学術総会
  • Place of Presentation: 東北大学
  • Year and Date: 20140100
• [Presentation] Species difference in Tryptophan metabolism (2013)
  • Author(s): Murakami Y, Saito K
  • Organizer: The 13th satellite symposium of the Japanese Society for Tryptophan Research
  • Place of Presentation: Queensland, Australia
  • Year and Date: 20131100
• [Presentation] インターフェロン誘発性抑うつ発症時のトリプトファン代謝産物動態解析 (2013)
  • Author(s): 村上由希、石橋貴明、安藤量基、富田栄一、竹村正男、山本康子、齋藤邦明
  • Organizer: 日本トリプトファン研究会第35回学術集会
  • Place of Presentation: 京都大学
  • Year and Date: 20130900
• [Book] Septic Encephalopathy (2013)
  • Author(s): Imamura Y, Hori S, Matsumoto N, Yamakawa K, Nakagawa J, Shimazaki J, Wang H, Itou J, Murakami Y, Mitani S, Ogura H, Shimazu T, Seiyam A
  • Publisher: NOVA Publishers
• [Book] Tumor Necrosis Factor-Alpha Related Signal Pathways and Neuronal Diseases (2013)
  • Author(s): Murakami Y, Imamura Y, Mitani S, Hoshi M, Arioka Y, Yamamoto Y, Seiyama A, Saito K
  • Publisher: NOVA Publishers