Tryptophan metabolic profile is effective for preemptive medicine in depression symptoms

• Project/Area Number: 15H03086
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied health science
• Research Institution: Fujita Health University
• Principal Investigator: Saito Kuniaki 藤田保健衛生大学, 保健学研究科, 教授 (80262765)
• Co-Investigator(Kenkyū-buntansha): 山本 康子 藤田保健衛生大学, 医療科学部, 准教授 (00331869) ; 藤垣 英嗣 藤田保健衛生大学, 医療科学部, 講師 (00612631) ; 石川 浩章 藤田保健衛生大学, 保健学研究科, 准教授 (50321013)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥16,380,000 (Direct Cost: ¥12,600,000、Indirect Cost: ¥3,780,000); Fiscal Year 2017: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2016: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000)
• Keywords: 先制医療 / バイオマーカー / 抑うつ / トリプトファン代謝産物 / ビッグデータ解析 / ストレス / ビックデータ / メタボローム

Outline of Final Research Achievements

The risk for developing mental illnesses such as depression is caused by a combination of genetic, biological, environmental, and psychological factors. The Bio-Resources/Database are very important for the establishment of preemptive medicine and understanding the mechanisms of the developmental origins of mental illnesses. In the present study, we established the bio-resources/database comprising personal health records (PHR), such as individual health/medical records including daily diet, exercise, General Health Questionnaire (GHQ) and Center for Epidemiological Studies-Depression (CES-D), taken from the same individuals with bio-resources (the bank serum of the Resource Center for Health Science (RECHS)). With using these bio-resources/database, metabolomics analysis revealed that change in tryptophan metabolic profile correlated with the depression score, and we established the disease-specific marker in depression which enabled preemptive medicine.

Academic Significance and Societal Importance of the Research Achievements

本研究では、健康状態や食習慣、ストレス情報を含む環境因子等を電子情報として統合・管理する暦年的健常人データベースの構築を行った。また本データベースを用いた解析により、抑うつ病態における先制医療を可能とするためにトリプトファン代謝産物の変動が有効であることが示唆された。本研究により構築された暦年的健常人データベースは、今後も様々な疾患の先制医療を可能とする新規マーカー検索につながる検討であり、広く臨床に貢献できる検討であると考える。

Research Products

• [Journal Article] Excess maternal fructose consumption impairs hippocampal function in offspring via epigenetic modification of BDNF promoter. (2018)
  • Author(s): Yamazaki M, Yamada H, Munetsuna E, Ishikawa H, Mizuno G, Mukuda T, Mouri A, Nabeshima T, Saito K, Suzuki K, Hashimoto S, Ohashi K.
  • Journal Title: FASEB J. Volume: 32 Issue: 5 Pages: 2549-2562
  • DOI: 10.1096/fj.201700783rr
  • Peer Reviewed / Open Access
• [Journal Article] Astroglial major histocompatibility complex class I following immune activation leads to behavioral and neuropathological changes. (2018)
  • Author(s): A Sobue, N Ito, T Nagai, W Shan, K Hada, Nakajima A, Y Murakami, A Mouri, Y Yamamoto, T Nabeshima, K Saito, K Yamada
  • Journal Title: Glia Volume: 66 Issue: 5 Pages: 1034-52
  • DOI: 10.1002/glia.23299
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Higher levels of progranulin in cerebrospinal fluid of patients with lymphoma and carcinoma with CNS metastasis (2018)
  • Author(s): Kimura Akio、Takemura Masao、Serrero Ginette、Yoshikura Nobuaki、Hayashi Yuichi、Saito Kuniaki、Inuzuka Takashi
  • Journal Title: Journal of Neuro-Oncology Volume: 137 Issue: 3 Pages: 455-462
  • DOI: 10.1007/s11060-017-2742-z
  • Peer Reviewed
• [Journal Article] Association between increased serum GP88 (progranulin) concentrations and prognosis in patients with malignant lymphomas. (2017)
  • Author(s): Yamamoto Y, Goto N, Takemura M, Yamasuge W, Yabe K, Takami T, Miyazaki T, Takeuchi T, Shiraki M, Shimizu M, Adachi S, Saito K, Shibata Y, Nakamura N, Hara T, Serrero G, Saito K, Tsurumi H.
  • Journal Title: Clin Chim Acta Volume: 473 Pages: 139-146
  • DOI: 10.1016/j.cca.2017.07.024
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Sake lees extract improves hepatic lipid accumulation in high fat diet-fed mice. (2017)
  • Author(s): Kubo H, Hoshi M, Matsumoto T, Irie M, Oura S, Tsutsumi H, Hata Y, Yamamoto Y, Saito K
  • Journal Title: Lipids Health Dis. Volume: 16(1) Issue: 1 Pages: 106-106
  • DOI: 10.1186/s12944-017-0501-y
  • Peer Reviewed / Open Access
• [Journal Article] Kynurenine 3-monooxygenase is implicated in antidepressants-responsive depressive-like behaviors and monoaminergic dysfunctions (2017)
  • Author(s): Tashiro T , Murakami Y , Mouri A , Imamura Y, Nabeshima T, Yamamoto, Y , Saito, K
  • Journal Title: BEHAVIOURAL BRAIN RESEARCH Volume: 317 Pages: 279-285
  • DOI: 10.1016/j.bbr.2016.09.050
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Effect of water-immersion restraint stress on tryptophan catabolism through the kynurenine pathway in rat tissues. (2017)
  • Author(s): Ohta Y, Kubo H, Yashiro K, Ohashi K, Tsuzuki Y, Wada N, Yamamoto Y, Saito K.
  • Journal Title: J Physiol Sci. Volume: 67(3) Issue: 3 Pages: 361-372
  • DOI: 10.1007/s12576-016-0467-y
  • NAID: 40021176369
  • Peer Reviewed
• [Journal Article] Effect of water-immersion restraint stress on tryptophan catabolism through the kynurenine pathway in rat tissues (2017)
  • Author(s): Ohta Y , Kubo H , Yashiro K , Ohashi K , Tsuzuki Y , Wada N , Yamamoto Y , Saito, K
  • Journal Title: JOURNAL OF PHYSIOLOGICAL SCIENCES Volume: 67 Pages: 361-372
  • NAID: 40021176369
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Increased cerebrospinal fluid progranulin correlates with interleukin-6 in the acute phase of neuromyelitis optica spectrum disorder. (2017)
  • Author(s): Kimura A, Takemura M, Saito K, Serrero G, Yoshikura N, Hayashi Y, Inuzuka T.
  • Journal Title: JOURNAL OF NEUROIMMUNOLOGY Volume: 305 Pages: 175-181
  • DOI: 10.1016/j.jneuroim.2017.01.006
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Absence of kynurenine 3-monooxygenase reduces mortality of acute viral myocarditis in mice (2017)
  • Author(s): Kubo H, Hoshi M, Mouri A, Tashita C, Yamamoto Y, Nabeshima T, Saito K.
  • Journal Title: IMMUNOLOGY LETTERS Volume: 181 Pages: 94-100
  • DOI: 10.1016/j.imlet.2016.11.012
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Association between naturally occurring anti-amyloid β autoantibodies and medial temporal lobe atrophy in Alzheimer's disease (2017)
  • Author(s): .Kimura A, Takemura M, Saito K, Yoshikura N, Hayashi Y, Inuzuka T.
  • Journal Title: J NEUROL NEUROSUR PSYCHIATRY Volume: 88 Issue: 2 Pages: 126-131
  • DOI: 10.1136/jnnp-2016-313476
  • Peer Reviewed / Open Access
• [Journal Article] Serum concentrations of l-kynurenine predict clinical outcomes of patients with peripheral T-cell lymphoma, not otherwise specified. (2016)
  • Author(s): Shibata Y, Hara T, Matsumoto T, Nakamura N, Nakamura H, Ninomiya S, Kitagawa J, Goto N, Nannya Y, Ito H, Kito Y, Miyazaki T, Takeuchi T, Saito K, Seishima M, Takami T, Moriwaki H, Shimizu M, Tsurumi H.
  • Journal Title: Hematological Oncology Volume: - Issue: 4 Pages: 637-644
  • DOI: 10.1002/hon.2318
  • Peer Reviewed / Open Access
• [Journal Article] L-Tryptophan-kynurenine pathway enzymes are therapeutic target for neuropsychiatric diseases: Focus on cell type differences. (2016)
  • Author(s): Fujigaki H, Yamamoto Y, Saito K
  • Journal Title: Neuropharmacology. Volume: 印刷中 Pages: 264-274
  • DOI: 10.1016/j.neuropharm.2016.01.011
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Depressive symptoms as a side effect of Interferon-α therapy induced by induction of indoleamine 2,3-dioxygenase 1. (2016)
  • Author(s): Murakami Y, Ishibashi T, Tomita E, Imamura Y, Tashiro T, Watcharanurak K, Nishikawa M, Takahashi Y, Takakura Y, Mitani S, Fujigaki H, Ohta Y, Kubo H, Mamiya T, Nabeshima T, Kim HC, Yamamoto Y, Saito K.
  • Journal Title: SCIENTIFIC REPORTS Volume: 6 Issue: 1 Pages: 29920-29920
  • DOI: 10.1038/srep29920
  • NAID: 120006323748
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] L-Tryptophan-kynurenine pathway enzymes are therapeutic target for neuropsychiatric diseases: Focus on cell type differences. Neuropharmacology. (2016)
  • Author(s): Fujigaki H, Yamamoto Y, Saito K.
  • Journal Title: j.neuropharm. Volume: S0028-3908(16) Pages: 30011-9
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Prognostic value of the combination of serum l-kynurenine level and indoleamine 2,3-dioxygenase mRNA expression in acute myeloid leukemia. (2016)
  • Author(s): Hara T, Matsumoto T, Shibata Y, Nakamura N, Nakamura H, Ninomiya S, Kitagawa J, Nannya Y, Shimizu M, Ito H, Saito K, Tsurumi H.
  • Journal Title: Leuk Lymphoma. Volume: 13 Pages: 1-4
  • Peer Reviewed
• [Presentation] Depressive symptoms and L-Tryptophan -Kynurenine pathway metabolism focus on neuro-inflammation. (2017)
  • Author(s): Kuniaki Saito
  • Organizer: The 5th Congress of Asian College pof Neuropsychopharmacology
  • Int'l Joint Research
• [Presentation] 脳神経疾患における治療標的としてのトリプトファン-キヌレニン代謝酵素 (2017)
  • Author(s): 齋藤邦明
  • Organizer: 第23回脳の医学・生物学研究会
• [Presentation] アストログリアにおけるMHCIの発現とその行動学的・神経病理学的影響 (2017)
  • Author(s): 祖父江顕,伊藤教道,羽田和弘,中島晶,村上由希,毛利彰宏,山本康子,鍋島俊隆,齋藤邦明,永井拓,山田清文
  • Organizer: 第39回日本生物学的精神医学会・第47回日本神経精神薬理学会 合同年会
• [Presentation] Kynurenine 3-monooxygenase遺伝子R452C変異解析の基礎的検討． (2017)
  • Author(s): 藤垣英嗣、吉田幸弘、山本康子、齋藤邦明
  • Organizer: 第57回日本臨床化学会年次学術集会
• [Presentation] 酵素法を用いたキヌレニン定量法の開発． (2017)
  • Author(s): 吉田幸弘、藤垣英嗣、山本康子、齋藤邦明
  • Organizer: 第57回日本臨床化学会年次学術集会
• [Presentation] RA患者の血中インフリキシマブ濃度測定の意義 (2017)
  • Author(s): 竹村正男、佐藤正夫、伊藤弘養、 清島 満、齋藤邦明
  • Organizer: 第64回日本臨床検査医学会学術集会
• [Presentation] Kynurenine aminotransferase 2を用いたキヌレニン測定法の開発． (2017)
  • Author(s): 吉田幸弘、藤垣英嗣、山﨑杏佳、山本康子、齋藤邦明
  • Organizer: 第38回日本トリプトファン研究会学術集
• [Presentation] 先制医療の実現のために ～次世代創薬・診断薬開発～ (2017)
  • Author(s): 齋藤邦明
  • Organizer: 臨床検査薬協会・技術委員会総会
  • Place of Presentation: ヒューリックカンファレンスルーム(東京
  • Invited
• [Presentation] 周産期における抑うつにおけるトリプトファン代謝関連分子の変化 (2016)
  • Author(s): 勅使河原知明、久保緋紗子、毛利彰宏、鍋島俊隆、尾崎紀夫、山本康子、齋藤邦明
  • Organizer: 第56回日本臨床化学会学術大会
  • Place of Presentation: 熊本県民交流館パレア(熊本）
• [Presentation] 周産期における抑うつにおけるユビキチン化セロトニントランスポーターの変化 (2016)
  • Author(s): 毛利彰宏、椎野智子、勅使河原知明、山本康子、野田幸裕、尾崎紀夫、齋藤邦明、鍋島俊隆 「
  • Organizer: 第56回日本臨床化学会学術大会
  • Place of Presentation: 熊本県民交流館パレア(熊本）
• [Presentation] マウス致死性敗血症モデルにおけるインドールアミン酸素添加酵素の役割について」 (2016)
  • Author(s): 星雅人、久保緋紗子、毛利彰宏、勅使河原知明、山菅和可菜、和田直也、山本康子、鍋島俊隆、毛利彰宏
  • Organizer: 第37回日本トリプトファン研究開学術集会
  • Place of Presentation: 東京農業大学
• [Presentation] Absence of kynurenine 3-monooxygebase reduces mortality of accute viral myocarditis in mice (2016)
  • Author(s): 久保緋紗子、星雅人、毛利彰宏、田下智栄子、勅使河原知明、山菅和可菜、和田直也、山本康子、鍋島俊隆、毛利彰宏
  • Organizer: 第37回日本トリプトファン研究開学術集会
  • Place of Presentation: 東京農業大学
• [Presentation] 先制医療を実現するためのバイオバンク (2015)
  • Author(s): 斉藤邦明
  • Organizer: 第62回日本臨床検査医学会学術集会
  • Place of Presentation: 長良川国際会議場（岐阜）
  • Year and Date: 2015-11-21
• [Presentation] 健常時からの暦年的バイオバンクの活用 -代謝変容に着目したバイオマーカー検索- (2015)
  • Author(s): 斉藤邦明
  • Organizer: 第55回日本臨床化学会年次学術集会
  • Place of Presentation: 大阪大学コンベンションセンター（吹田市）
  • Year and Date: 2015-10-31
• [Presentation] The role of L-tryptophan metabolism via indoleamine 2,3-dioxygenase on cytokine-induced depressive symptoms (2015)
  • Author(s): Saito K
  • Organizer: ISTRY conference Symposium Pathology III
  • Place of Presentation: Grand Rapids（ USA）
  • Year and Date: 2015-09-16
  • Int'l Joint Research / Invited
• [Presentation] 先制医療実現のために ー不健康を科学するー (2015)
  • Author(s): 斉藤邦明
  • Organizer: 日本健康科学会第31回学術集会・次期学術集会長講演
  • Place of Presentation: ホテルグランドヒル市ヶ谷（東京）
  • Year and Date: 2015-08-21
  • Invited
• [Patent(Industrial Property Rights)] 精神疾患の判定方法 (2018)
  • Inventor(s): 2018
  • Industrial Property Rights Holder: 小畠 伸三
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2018-051017
  • Filing Date: 2018