Search for predictive biomarkers on mood changes of bipolar disorder by metabolome analysis.

• Project/Area Number: 16K19257
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Epidemiology and preventive medicine
• Research Institution: Osaka City University
• Principal Investigator: DEGUCHI YASUHIKO 大阪市立大学, 大学院医学研究科, 講師 (30721790)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2017: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
• Keywords: 双極性障害 / 自殺予防 / バイオマーカー / うつ病 / メタボローム解析

Outline of Final Research Achievements

The increased levels of nervonic acid in patients with major depressive disorder (MDD) compared with controls and patients with bipolar disorder (BD). Nervonic acid levels were increased in the depressive state in patients with MDD compared with the levels in the remission state in patients with MDD and the depressive state in patients with BD. Circulating mitochondrial DNA (mtDNA) levels showed a positive correlation with IL-4 in patients with MDD. Patients with MDD and BD showed significantly lower plasma mtDNA levels than controls. We collected plasma samples from depressive state and remitted state of the same BD patients and matched healthy controls. We analyzed the metabolites and there was no significant difference in metabolites between the groups.

Academic Significance and Societal Importance of the Research Achievements

血漿ネルボン酸が、うつ病の状態像を示すバイオマーカー候補、うつ病と双極性障害の鑑別に寄与するバイオマーカー候補となりうる可能性が示された。ミトコンドリアDNAがうつ病の炎症に関与している可能性が示された。

Research Products

• [Journal Article] Plasma Nervonic Acid Is a Potential Biomarker for Major Depressive Disorder: A Pilot Study. (2018)
  • Author(s): Kageyama Y, Kasahara T, Nakamura T, Hattori K, Deguchi Y, Tani M, Kuroda K, Yoshida S, Goto YI, Inoue K, Kato T
  • Journal Title: The international journal of neuropsychopharmacology Volume: 21 Pages: 207-215
  • Peer Reviewed / Open Access
• [Journal Article] The relationship between circulating mitochondrial DNA and inflammatory cytokines in patients with major depression. (2017)
  • Author(s): Kageyama Y, Kasahara T, Kato M, Sakai S, Deguchi Y, Tani M, Kuroda K, Hattori K, Yoshida S, Goto Y, Kinoshita T, Inoue K, Kato T
  • Journal Title: Journal of affective disorders Volume: 233 Pages: 15-20
  • Peer Reviewed / Open Access
• [Journal Article] Search for plasma biomarkers in drug-free patients with bipolar disorder and schizophrenia using metabolome analysis (2017)
  • Author(s): Kageyama Y, Kasahara T, Morishita H, Mataga N, Deguchi Y, Tani M, Kuroda K, Hattori K, Yoshida S, Inoue K, Kato T
  • Journal Title: Psychiatry and clinical neuroscience Volume: 71 Issue: 2 Pages: 115-121
  • DOI: 10.1111/pcn.12461
  • Peer Reviewed / Open Access
• [Journal Article] 新規抗うつ薬で強い副作用が出現し低用量のイミプラミンへの切り替えが有効であった重症うつ病の1症例 (2017)
  • Author(s): 門脇彩, 出口裕彦, 柳川枝里佳, 野木優香子, 井上幸紀
  • Journal Title: 臨床精神医学 Volume: 46 Pages: 1031-1036
  • NAID: 40021294163
  • Peer Reviewed
• [Journal Article] Paroxetine 増量後10日目にセロトニン症候群を呈した1 例 (2017)
  • Author(s): 野木優香子,林皓章,深田亮介,出口裕彦,岩﨑進一,木岡哲郎,井上幸紀
  • Journal Title: 精神科治療学 Volume: 32 Pages: 127-131
  • Peer Reviewed
• [Presentation] 血漿代謝産物を利用した気分障害のバイオマーカー (2018)
  • Author(s): 影山祐紀、笠原和起、中村健道、服部功太郎、出口裕彦、 谷宗英、黒田健治、吉田寿美子、後藤 雄一、井上幸紀、加藤忠史
  • Organizer: 第40回日本生物学的精神医学会
• [Presentation] Search for Plasma Biomarkers of Depression by Metabolome Analysis in an Animal Model and Clinical Samples (2017)
  • Author(s): Yuki Kageyama, Takaoki Kasahara, Takemichi Nakamura, Yasuhiko Deguchi, Munehide Tani, Kenji Kuroda, Kotaro Hattori, Sumiko Yoshida, Kenji Kuroda, Koki Inoue, Tadafumi Kato
  • Organizer: PCS International Conference of Neuroscience
  • Int'l Joint Research
• [Presentation] 気分障害の診断バイオマーカー (2017)
  • Author(s): 影山祐紀、笠原和起、中村健道、服部功太郎、出口裕彦、谷宗英、黒田健治、吉田寿美子、後藤雄一、井上幸紀、加藤忠史
  • Organizer: 第36回躁うつ病の薬理・生化学的研究懇話会
• [Presentation] The relationship between circulating mitochondrial DNA and inflammatory cytokines in patients with major depression. (2017)
  • Author(s): Yuki Kageyama, Takaoki Kasahara, Masaki Kato, Shiho Sakai, Yasuhiko Deguchi, Munehide Tani, Kenji Kuroda, Kotaro Hattori, Sumiko Yoshida, Kenji Kuroda, Yu-ichi Goto, Toshihiko Kinoshita, Koki Inoue, Tadafumi Kato
  • Organizer: Neuroscience2017