Searching for the suicide-related blood biomarker and suicide risk

• Project/Area Number: 15K19239
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hygiene and public health
• Research Institution: National Center of Neurology and Psychiatry (2016-2018); Hirosaki University (2015)
• Principal Investigator: Tsuchimine Shoko 国立研究開発法人国立精神・神経医療研究センター, 神経研究所 疾病研究第三部, 科研費研究員 (60649044)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 血中バイオマーカー / うつ病 / 人格特性 / 遺伝子多型 / 自殺 / バイオマーカー / 抗うつ薬 / CREB / pCREB / オレキシン / 躁うつ病 / 脳由来神経栄養因子 / 多価不飽和脂肪酸 / 炎症性サイトカイン / パーソナリティ / サイトカイン

Outline of Final Research Achievements

1) Free testosterone was slightly but significantly associated with extravagance (NS3), a subscale of novelty seeking. These results indicate the possibility that free testosterone has a small influence on novelty seeking in healthy Japanese male subjects. 2) Serum levels of DHA, AA, and folate levels in the patients group were statistically lower than those in the control group, while serum levels of BDNF were not different between cases and controls. 3) Mean orexin-A levels were significantly different across the four diagnostic groups. In particular, the patients with BD showed significantly lower orexin-A levels than did the controls.

Academic Significance and Societal Importance of the Research Achievements

現在までのところ自殺リスクの高い者を認識するツールはなく心理検査や臨床症状から判断する他ない。ゆえに血液から自殺に関するより量的で客観的指標（バイオマーカー）を確立できれば、心理検査および臨床症状の評価と組み合わせた包括的な自殺予防対策が可能となり、自殺行動に対してハイリスクな患者のスクリーニングや効果的かつ早期の介入を行うことができる。

Research Products

• [Journal Article] Reduced plasma orexin-A levels in patients with bipolar disorder (2019)
  • Author(s): Shoko Tsuchimine, Kotaro Hattori, Miho Ota, Shinsuke Hidese, Toshiya Teraishi, Daimei Sasayama, Hiroaki Hori, Takamasa Noda, Sumiko Yoshida, Fuyuko Yoshida, Hiroshi Kunugi
  • Journal Title: Neuropsychiatric Disease and Treatment Volume: 印刷中
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Increased levels of CREB in major depressive patients with antidepressant treatment. (2018)
  • Author(s): Tsuchimine S, Sugawara N, Yasui-Furukori N.
  • Journal Title: Psychiatry Research Volume: 263 Pages: 296-297
  • DOI: 10.1016/j.psychres.2017.12.077
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Effects of Cytochrome P450 (CYP) 2C19 Genotypes on Steady-State Plasma Concentrations of Escitalopram and its Desmethyl Metabolite in Japanese Patients With Depression. (2018)
  • Author(s): Tsuchimine S, Ochi S, Tajiri M, Suzuki Y, Sugawara N, Inoue Y, Yasui-Furukori N.
  • Journal Title: Therapeutic Drug Monitoring Volume: 40 Issue: 3 Pages: 356-361
  • DOI: 10.1097/ftd.0000000000000506
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Serum x03C9;-3 and x03C9;-6 Fatty Acids Are Not Associated with Personality Traits in Healthy Japanese Young People. (2016)
  • Author(s): Tsuchimine S, Kaneda A, Yasui-Furukori N.
  • Journal Title: Neuropsychobiology. Volume: 73 Issue: 4 Pages: 249-53
  • DOI: 10.1159/000446920
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Influence of the cytochrome P450 2D6 *10/*10 genotype on the pharmacokinetics of paroxetine in Japanese patients with major depressive disorder: a population pharmacokinetic analysis. (2016)
  • Author(s): Nishimura M, Ueda M, Saruwatari J, Nakashima H, Ogusu N, Aoki A, Tsuchimine S, Matsuda K, Iwashita K, Ono T, Oniki K, Shimoda K, Yasui-Furukori N.
  • Journal Title: Pharmacogenet Genomics. Volume: 26 Issue: 9 Pages: 403-13
  • DOI: 10.1097/fpc.0000000000000228
  • Peer Reviewed
• [Journal Article] Items of the Montgomery-Asberg Depression Rating Scale Associated With Response to Paroxetine Treatment in Patients With Major Depressive Disorder. (2016)
  • Author(s): Tomita T, Sato Y, Nakagami T, Tsuchimine S, Kaneda A, Kaneko S, Nakamura K, Yasui-Furukori N.
  • Journal Title: Clin Neuropharmacol. Volume: 39 Pages: 135-9
  • Peer Reviewed
• [Journal Article] Characteristics of Escitalopram Discontinuation Syndrome: A Preliminary Study. (2016)
  • Author(s): Yasui-Furukori N, Hashimoto K, Tsuchimine S, Tomita T, Sugawara N, Ishioka M, Nakamura K.
  • Journal Title: Clin Neuropharmacol. Volume: 39 Issue: 3 Pages: 125-7
  • DOI: 10.1097/wnf.0000000000000139
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Glutathione S-transferase K1 genotype and overweight status in schizophrenia patients: A pilot study. (2016)
  • Author(s): Oniki K, Kamihashi R, Tomita T, Ishioka M, Yoshimori Y, Osaki N, Tsuchimine S, Sugawara N, Kajiwara A, Morita K, Miyata K, Otake K, Nakagawa K, Ogata Y, Saruwatari J, Yasui-Furukori N.
  • Journal Title: Psychiatry Res. Volume: 239 Pages: 190-195
  • DOI: 10.1016/j.psychres.2016.03.025
  • Peer Reviewed / Open Access
• [Journal Article] The effects of fluvoxamine on the steady-state plasma concentrations of escitalopram and desmethylescitalopram in depressed Japanese patients. (2016)
  • Author(s): Yasui-Furukori N, Tsuchimine S, Kubo K, Ishioka M, Nakamura K, Inoue Y.
  • Journal Title: Therapeutic Drug Monitoring of Everolimus Volume: Epub ahead of print Issue: 4 Pages: 483-6
  • DOI: 10.1097/ftd.0000000000000303
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The gamma-interferon (IFN-γ) gene +874 T>A polymorphism is not associated with personality traits in healthy Japanese subjects. (2016)
  • Author(s): Tsuchimine S, Kaneda A, Yasui-Furukori N.
  • Journal Title: Brain, Behavior, and Immunity Volume: 51 Pages: 268-9
  • DOI: 10.1016/j.bbi.2015.08.018
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Glutathione S-transferase K1 genotype and overweight status in schizophrenia patients: A pilot study. (2016)
  • Author(s): Oniki K, Kamihashi R, Tomita T, Ishioka M, Yoshimori Y, Osaki N, Tsuchimine S, Sugawara N, Kajiwara A, Morita K, Miyata K, Otake K, Nakagawa K, Ogata Y, Saruwatari J, Yasui-Furukori N.
  • Journal Title: Psychiatric Research Volume: 239 Pages: 190-5
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Factors Affecting Steady-state Plasma Concentrations of Enantiomeric Mirtazapine and its Desmethylated Metabolites in Japanese Psychiatric Patients. (2015)
  • Author(s): Hayashi Y, Watanabe T, Aoki A, Ishiguro S, Ueda M, Akiyama K, Kato K, Inoue Y, Tsuchimine S, Yasui-Furukori N, Shimoda K.
  • Journal Title: Pharmacopsychiatry Volume: 48 Issue: 07 Pages: 279-85
  • DOI: 10.1055/s-0035-1565069
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Attitudes toward Placebo-Controlled Clinical Trials of Patients with Schizophrenia in Japan. (2015)
  • Author(s): Sugawara N, Ishioka M, Tsuchimine S, Tsuruga K, Sato Y, Furukori H, Kudo S, Tomita T, Nakagami T, Yasui-Furukori N.
  • Journal Title: PLoS One Volume: 10 Issue: 11 Pages: e0143356-e0143356
  • DOI: 10.1371/journal.pone.0143356
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] 児童思春期うつ病における多価不飽和脂肪酸とBDNFの役割について (2015)
  • Author(s): 古郡規雄、土嶺章子
  • Journal Title: 日本生物学的精神医学会誌 Volume: 26 Pages: 205-11
  • NAID: 130005395610
  • Peer Reviewed
• [Presentation] Increased levels of CREB and pCREB in major depressive patients with antidepressant treatment (2018)
  • Author(s): Shoko Tsuchimine, Norio Sugawara, Hiroshi Kunugi, Norio Yasui-Furukori
  • Organizer: 国際神経精神薬理学会
  • Int'l Joint Research
• [Presentation] Reduced plasma orexin-A levels in patients with schizophrenia, major depressive disorder and bipolar disorder (2018)
  • Author(s): Shoko Tsuchimine, Kotaro Hattori, Miho Ota, Shinsuke Hidese, Toshida Teraishi, Daimei Sasayama, Hiroaki Hori, Takamasa Noda, Sumiko Yoshida, Fuyuko Yoshida, Hiroshi Kunugi
  • Organizer: 日本神経科学会
• [Presentation] 慢性拘束ストレス負荷によるうつ様行動に対する (2018)
  • Author(s): 土嶺 章子、千葉 秀一、吉村 文、鈴木 仁美、大橋 一徳、中島 進吾、惣谷 和広、功刀 浩
  • Organizer: 躁うつ病懇話会
• [Presentation] 精神疾患患者における血漿中オレキシン濃度と臨床症状との関連 (2017)
  • Author(s): 土嶺章子、服部功太郎、太田深秀、秀瀬真輔、寺石俊也、篠山大明、堀弘明、野田隆政、吉田寿美子、吉田冬子、功刀浩
  • Organizer: 第36回躁うつ病の薬理・生化学的研究懇話会
• [Presentation] 抗うつ薬治療中のうつ病患者におけるT細胞由来CREBとpCREBの比較検討 (2017)
  • Author(s): 土嶺章子、菅原典夫、功刀浩、古郡規雄
  • Organizer: 第27回臨床精神神経薬理学会
• [Presentation] ミルタザピン治療がうつ病関連バイオマーカーに与える変化について (2016)
  • Author(s): 土嶺章子、菅原典夫、佐藤靖、井上義政、古郡規雄
  • Organizer: 第26回日本臨床精神神経薬理学会
  • Place of Presentation: ホルトホール大分
  • Year and Date: 2016-11-17
• [Presentation] Effect of CYP2C19 genotype on steady-state plasma concentrations of escitalopram and desmethyl metabolite in Japanese depressed patients (2016)
  • Author(s): Shoko Tsuchimine, Yoshimasa Inoue, Shinichiro Ochi, Yutaro Suzuki, Misuzu Tajiri, Norio Yasui-Furukori
  • Organizer: 30th CINP World Congress of Neuropsychopharmacology
  • Place of Presentation: COEX (Seoul, Korea)
  • Year and Date: 2016-07-03
  • Int'l Joint Research
• [Presentation] エスシタロプラムの定常状態血中濃度とCYP2C19多型との関係 (2015)
  • Author(s): 土嶺章子、越智紳一郎、田尻美寿々、井上義政、鈴木雄太郎、古郡規雄
  • Organizer: 臨床精神神経薬理学会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2015-10-29
• [Funded Workshop] 30th CINP World Congress of Neuropsychopharmacology (2016)
  • Place of Presentation: COEX
  • Year and Date: 2016-07-03