Development of a treatment depression with mixed feature by a biomarker-based randomized controlled trial

• Project/Area Number: 15K09813
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Kansai Medical University
• Principal Investigator: KATO Masaki 関西医科大学, 医学部, 准教授 (00351510)
• Co-Investigator(Kenkyū-buntansha): 堀 輝 産業医科大学, 医学部, 講師 (50421334) ; 阿竹 聖和 産業医科大学, 医学部, 助教 (80721761) ; 西田 圭一郎 関西医科大学, 医学部, 非常勤講師 (40567567) ; 吉村 玲児 産業医科大学, 医学部, 教授 (90248568) ; 松田 文彦 京都大学, 医学研究科, 教授 (50212220)
• Project Period (FY): 2015-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2017: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2016: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000); Fiscal Year 2015: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
• Keywords: 個別化医療 / うつ病 / プレシジョンメディスン / 薬理遺伝 / miRNA / メチレーション / 治療反応 / プレシジョンメディシン / 混合性の特徴 / 治療抵抗性 / 無作為割付比較試験 / 遺伝子多型 / 認知機能 / pharmacogenomics

Outline of Final Research Achievements

Although there are high expectations for the implementation of precision medicine in psychiatry, a multifaceted approach needs to be persistently continued in this field, where the pathology is still unexplored and sampling of lesions is not possible. In this study, we focused on the genome, methylation, miRNAs, mitochondrial DNA, and clustering of clinical symptoms among the markers that are associated with the therapeutic response of antidepressants and may serve as the basis for drug selection and examined them in detail.

Academic Significance and Societal Importance of the Research Achievements

ゲノムやmiRNA、mtDNA、メチレーション、大規模臨床データを用いて、治療反応予測、治療選択の個別化を目指したいくつかの研究から、そこに寄与する可能性のあるいくつかの因子や関連するパスウェイが同定された。
特に、これまで幼少期の環境因を評価できる可能性のある、miRNAやメチレーションにより、適切な抗うつ薬を選択できる可能性が示唆されたのは興味深いと考える。ゲノム情報と合わせて、関連するパスウェイを更に研究すること、また長期的経過との関連も評価することで、更なる適切な治療に結実すると考える。

Research Products

• [Journal Article] Brain Volume-Related Polymorphisms of the Glycogen Synthase Kinase-3β Gene and Their Effect on Antidepressant Treatment in Major Depressive Disorder (2019)
  • Author(s): Sunada Naotaka、Takekita Yoshiteru、Nonen Shinpei、Wakeno Masataka、Koshikawa Yosuke、Ogata Haruhiko、Kinoshita Toshihiko、Kato Masaki
  • Journal Title: Neuropsychobiology Volume: 78 Issue: 3 Pages: 136-144
  • DOI: 10.1159/000500614
  • Peer Reviewed
• [Journal Article] The association of obesity and coronary artery disease genes with response to SSRIs treatment in major depression (2019)
  • Author(s): Amare AT, Schubert KO, Tekola-Ayele F, Hsu Wang L, Kato M, Liu YL, Praphanphoj V, Stingl JC, Bobo WV, Tsai SJ, Kubo M, Klein TE, Weinshilboum RM, Biernacka JM, Baune BT.
  • Journal Title: J Neural Transm (Vienna) Volume: 126 Issue: 1 Pages: 35-45
  • DOI: 10.1007/s00702-018-01966-x
• [Journal Article] Association of the Polygenic Scores for Personality Traits and Response to Selective Serotonin Reuptake Inhibitors in Patients with Major Depressive Disorder (2018)
  • Author(s): Amare Azmeraw T.、Schubert Klaus、Mushiroda Taisei、Kato Masaki、Liu Yu-Li、Praphanphoj Verayuth、Stingl Julia C.、Bobo William V.、Tsai Shih-Jen、Kubo Michiaki、Klein Teri E.、Weinshilboum Richard M.、Biernacka Joanna M.、Baune Bernhard T.
  • Journal Title: Frontiers in Psychiatry Volume: 9 Pages: 59-65
  • DOI: 10.3389/fpsyt.2018.00065
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The relationship between circulating mitochondrial DNA and inflammatory cytokines in patients with major depression (2018)
  • Author(s): Kageyama Yuki、Kasahara Takaoki、Kato Masaki、Sakai Shiho、Deguchi Yasuhiko、Tani Munehide、Kuroda Kenji、Hattori Kotaro、Yoshida Sumiko、Goto Yuichi、Kinoshita Toshihiko、Inoue Koki、Kato Tadafumi
  • Journal Title: Journal of Affective Disorders Volume: 233 Pages: 15-20
  • DOI: 10.1016/j.jad.2017.06.001
  • Peer Reviewed / Open Access
• [Journal Article] Non response at week 4 as clinically useful indicator for antidepressant combination in major depressive disorder. A sequential RCT (2017)
  • Author(s): Kato Masaki、Takekita Yoshiteru、Koshikawa Yosuke、Sakai Shiho、Bandou Hiroki、Nishida Keiichiro、Sunada Naotaka、Onohara Ai、Hatashita Yoshiyuki、Serretti Alessandro、Kinoshita Toshihiko
  • Journal Title: J Psychiatr Res Volume: 89 Pages: 97-104
  • DOI: 10.1016/j.jpsychires.2017.02.003
  • Peer Reviewed
• [Journal Article] Therapeutic Response to Paroxetine in Major Depressive Disorder Predicted by DNA Methylation (2017)
  • Author(s): Takeuchi Naohiro、Nonen Shinpei、Kato Masaki、Wakeno Masataka、Takekita Yoshiteru、Kinoshita Toshihiko、Kugawa Fumihiko
  • Journal Title: Neuropsychobiology Volume: 75 Issue: 2 Pages: 81-88
  • DOI: 10.1159/000480512
  • Peer Reviewed
• [Journal Article] Polymorphism of rs3813034 in Serotonin Transporter Gene SLC6A4 Is Associated With the Selective Serotonin and Serotonin-Norepinephrine Reuptake Inhibitor Response in Depressive Disorder: Sequencing Analysis of SLC6A4. (2016)
  • Author(s): Nonen, Shinpei PhD, Kato, Masaki MD, PhD, Takekita, Yoshiteru MD, PhD, Wakeno, Masataka MD, PhD, Sakai, Shiho, Serretti, Alessandro MD, PhD, Kinoshita, Toshihiko MD, PhD
  • Journal Title: Journal of Clinical Psychopharmacology Volume: 36 Issue: 1 Pages: 27-31
  • DOI: 10.1097/jcp.0000000000000454
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Genetic variants in combination with early partial improvement as clinical utility predictor of treatment outcome in major depressive disorder. - The result of two pooled RCT (2015)
  • Author(s): Kato M, Serretti, A., Nonen S, Takekita Y, Wakeno M, Azuma J, Kinoshita T.
  • Journal Title: Translational Psychiatry Volume: 5 Issue: 2 Pages: 1-5
  • DOI: 10.1038/tp.2015.6
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] ゲノミクス-エピゲノミクス-インフォマティクスによる，精神科領域でのプレシジョンメディシンを目指 した臨床薬理学的研究 (2019)
  • Author(s): 加藤 正樹
  • Organizer: 第 40 回日本臨床薬理学会学術総会
  • Invited
• [Presentation] うつ病における SSRI とミルタザピンの治療効果予測因子としての miRNA 発現量の有用性 GUNDAM study より (2019)
  • Author(s): 加藤 正樹
  • Organizer: 第 40 回日本臨床薬理学会学術総
• [Presentation] 治療抵抗性抑うつに外来診療でできること。社会復帰を目指した診断と治療 (2019)
  • Author(s): 加藤 正樹
  • Organizer: 第16回日本うつ病学会総会
• [Presentation] Clustering Patients by Depression Symptoms May Predict Treatment Outcomes for Major Depressive Disorder: Patient-Level Meta-analysis of Venlafaxine Extended Release Trials. (2019)
  • Author(s): Masaki Kato, Yuko Asami, Dalia B Wajsbrot, Xuemei Wang, Matthieu Boucher, PhD,Rita Prieto, Elizabeth Pappadopulos
  • Organizer: 32nd European College of Neuropsychopharmacology Congress
  • Int'l Joint Research
• [Presentation] 幼少期の虐待や性格傾向とmiRNA発現量の関連及び薬物療法の治療効果予測因子の探索 ～Genotype Utility Needed for Depression Antidepressant Medication (GUNDAM) studyより～ (2019)
  • Author(s): 舩槻紀也、加藤正樹
  • Organizer: 第29回日本臨床精神神経薬理学会
• [Presentation] The relationship between circulating mitochondrial DNA and microRNA in patients with major depression (2019)
  • Author(s): Haruhiko Ogata, Koichiro Higasa, Tadafumi Kato, Yuki Kageyama, Hidetoshi Tahara, Akira Shimamoto, Yoshiteru Takekita, Hiroki Bando, Yosuke Koshikawa, Shiho Sakai, Keiichiro Nishida, Shinpei Nonen, Toshihiko Kinoshita, Masaki Kato
  • Organizer: 2019 World Congress of Psychiatric Genetics(WCPG)
  • Int'l Joint Research
• [Presentation] MicroRNA Profiles as Predictor of Phenotrypic Features of the Therapeutic Effect of Mirtazapine and SSRI in Mdd Patients.(GUNDAM study (2018)
  • Author(s): Masaki Kato, Haruhiko Ogata, Koichiro Higasa, Hidetoshi Tahara, Akira Shimamoto, Yoshiteru Tkekita, Hiroki Bandou, Yousuke Kosikawa, Shiho Sakai, Keiichiro Nishida, Shinpei Nonen, Toshihiko Kinoshita
  • Organizer: 2018 World Congress of Psychiatric Genetics(WCPG)
  • Int'l Joint Research
• [Presentation] PGx in Depression, Current Status and Future Prospects for Clinical Use (2018)
  • Author(s): Masaki Kato
  • Organizer: World Congress of Basic and Clinical Pharmacology(WCP)
  • Int'l Joint Research / Invited
• [Presentation] あなたの知らないゲノム薬理の世界 (2018)
  • Author(s): 加藤正樹
  • Organizer: 第114回日本精神神経学会学術総会
• [Presentation] うつ病プレシジョン・メディシンにおける薬理遺伝の現状 (2018)
  • Author(s): 加藤正樹
  • Organizer: 第28回臨床精神神経薬理学会・第48回日本神経精神薬理学会 合同年会
• [Presentation] 治療抵抗性抑うつに対し外来診療で出来る薬物療法 (2017)
  • Author(s): 加藤正樹
  • Organizer: 第113回日本精神神経学会学術総会
  • Invited
• [Presentation] うつ病における遺伝薬理学の現状 (2017)
  • Author(s): 加藤正樹
  • 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
  • Invited