Development of clinical tests to predict the severity of depression or suicidal ideation.

• Project/Area Number: 18K07417
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Kyushu University
• Principal Investigator: Setoyama Daiki 九州大学, 大学病院, 助教 (30550850)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: うつ病 / バイオマーカー / うつ病患者の多様性 / 血しょう代謝物 / 性格層別化 / 治療効果判定 / トリプトファン・キヌレニン代謝 / 性格・パーソナリティ / 治療効果 / 遊離型 / トリプトファン・キヌレニン経路 / 質量分析 / 代謝物バイオマーカー / 遊離型代謝物 / 血しょう / 層別化

Outline of Final Research Achievements

In this study, we validated the plasma metabolite biomarkers of depression that we have previously reported with a new approach. It was found that when stratified by their personality of depressive patients the biomarker ability to distinguish from healthy subjects is dramatically improved in some personality groups. Furthermore, we validated the effect of biomarkers on the treatment response to repeated transcranial magnetic stimulation (rTMS), a non-invasive treatment for depressive patients. Finally, we discovered that some of the tryptophan/kynurenine metabolites, which are thought to be established biomarkers of depression, are detected in the plasma macroprotein fractions, and identified a newly tryptophan-carrying protein other than albumin.

Academic Significance and Societal Importance of the Research Achievements

うつ病を始めとするメンタルヘルス分野に対して、客観的な臨床検査法の開発が世界規模で望まれている。うつ病と一言でいっても、様々なタイプが存在する。現在の抗うつ薬の多くはトリプトファン経路の代謝物をターゲットにしているが、効果の発現には個人差があるとされる。我々の研究は、性格の違いにより、うつ病のバイオタイプが異なるため、それぞれに異なる治療戦略が必要であることを示唆する。今後の研究の発展により、性格検査や採血により一人一人のバイオタイプを事前に把握することによる個別化医療の実現が期待できる。

Research Products

• [Int'l Joint Research] 上海交通大学新華病院/上海交通大学精神衛生中心(中国)
• [Journal Article] Personality classification enhances blood metabolome analysis and biotyping for major depressive disorders: two-species investigation (2021)
  • Author(s): Setoyama Daiki、Yoshino Atsuo、Takamura Masahiro、Okada Go、Iwata Masaaki、Tsunetomi Kyohei、Ohgidani Masahiro、Kuwano Nobuki、Yoshimoto Junichiro、Okamoto Yasumasa、Yamawaki Shigeto、Kanba Shigenobu、Kang Dongchon、Kato Takahiro A.
  • Journal Title: Journal of Affective Disorders Volume: 279 Pages: 20-30
  • DOI: 10.1016/j.jad.2020.09.118
  • Peer Reviewed / Open Access
• [Journal Article] Plasma acetylcholine and nicotinic acid are correlated with focused preference for photographed females in depressed males: an economic game study (2021)
  • Author(s): Kubo Hiroaki、Setoyama Daiki、Watabe Motoki、Ohgidani Masahiro、Hayakawa Kohei、Kuwano Nobuki、Sato-Kasai Mina、Katsuki Ryoko、Kanba Shigenobu、Kang Dongchon、Kato Takahiro A.
  • Journal Title: Scientific Reports Volume: 11 Issue: 1 Pages: 2199-2199
  • DOI: 10.1038/s41598-020-75115-4
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The changes in kynurenine metabolites induced by rTMS in treatment-resistant depression: A pilot study (2021)
  • Author(s): Tateishi H, Setoyama D, Kang D, Matsushima J, Kojima R, Fujii Y, Mawatari S, Kikuchi J, Sakemura Y, Fukuchi J, Shiraishi T, Maekawa T, Kato TA, Asami T, Mizoguchi Y, Monji A.
  • Journal Title: J Psychiatr Res . Volume: 138 Pages: 194-199
  • DOI: 10.1016/j.jpsychires.2021.04.009
  • Peer Reviewed / Open Access
• [Journal Article] Beta-hydroxybutyrate, an endogenous NLRP3 inflammasome inhibitor, attenuates anxiety-related behavior in a rodent post-traumatic stress disorder model (2020)
  • Author(s): Yamanashi Takehiko、Iwata Masaaki、Shibushita Midori、Tsunetomi Kyohei、Nagata Mayu、Kajitani Naofumi、Miura Akihiko、Matsuo Ryoichi、Nishiguchi Tsuyoshi、Kato Takahiro A.、Setoyama Daiki、Shirayama Yukihiko、Watanabe Ken、Shinozaki Gen、Kaneko Koichi
  • Journal Title: Scientific Reports Volume: 10 Issue: 1 Pages: 21629-21629
  • DOI: 10.1038/s41598-020-78410-2
  • Peer Reviewed / Open Access
• [Journal Article] Kynurenic acid is a potential overlapped biomarker between diagnosis and treatment response for depression from metabolome analysis. (2020)
  • Author(s): Erabi H, Okada G, Shibasaki C, Setoyama D, Kang D, Takamura M, Yoshino A, Fuchikami M, Kurata A, Kato TA, Yamawaki S, Okamoto Y.
  • Journal Title: Sci Rep. Volume: 10(1) Issue: 1 Pages: 16822-16822
  • DOI: 10.1038/s41598-020-73918-z
  • Peer Reviewed / Open Access
• [Journal Article] Suicide and Microglia: Recent Findings and Future Perspectives Based on Human Studies (2019)
  • Author(s): Suzuki H, Ohgidani M, Kuwano N, Chrétien F, Lorin de la Grandmaison G, Onaya M, Tominaga I, Setoyama D, Kang D, Mimura M, Kanba S, Kato TA*
  • Journal Title: Frontiers in Cellular Neuroscience Volume: 13 Pages: 31-31
  • DOI: 10.3389/fncel.2019.00031
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Development and validation of the 22-item Tarumi's modern-type depression trait scale; Avoidance of social roles, Complaint and low Self-esteem (TACS-22) (2019)
  • Author(s): Kato TA, Katsuki R, Kubo H, Shimokawa N, Sato-Kasai M, Hayakawa K, Kuwano N, Umene-akano W, Tateno M, Setoyama D, Kang D, Watabe M, Sakamoto S, Teo AR, Kanba S
  • Journal Title: Psychiatry and clinical neurosciences Volume: in press Issue: 8 Pages: 448-457
  • DOI: 10.1111/pcn.12842
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Tryptophan-kynurenine and lipid related metabolites as blood biomarkers for first-episode drug-naive patients with major depressive disorder: an exploratory pilot case-control study. (2018)
  • Author(s): Kuwano N, Kato TA, Setoyama D, Sato-Kasai M, Shimokawa N, Hayakawa K, Ohgidani M, Sagata N, Kubo H, Kishimoto J, Kang D, Kanba S
  • Journal Title: Journal of Affective Disorders Volume: 231 Pages: 74-82
  • DOI: 10.1016/j.jad.2018.01.014
  • Peer Reviewed
• [Presentation] 個々人のパーソナリティを加味したLCMSによる血液うつ病バイオマーカー研究 (2019)
  • Author(s): 瀬戸山大樹
  • Organizer: 第51回日本臨床検査自動化学会
• [Presentation] うつ病バイオマーカー探索のための血しょう代謝物の層別化解析法の提案 (2018)
  • Author(s): 瀬戸山大樹
  • Organizer: 第５8回臨床化学会年次学術集会
• [Presentation] 「強く自殺したい」と思うひとを検査で見つけたい-自殺念慮に相関する血液LC-MS解析 (2018)
  • Author(s): 瀬戸山大樹
  • Organizer: 第５０回日本臨床検査自動化学会
• [Presentation] メンタルヘルスの臨床検査における質量分析の役割 (2018)
  • Author(s): 瀬戸山大樹
  • Organizer: 第５8回臨床化学会年次学術集会
  • Invited
• [Book] 精神科（心療内科）診断バイオマーカー－うつ病の血液バイオマーカー開発の試み－ (2020)
  • Author(s): 瀬戸山大樹、加藤隆弘
  • Publisher: 科学評論社