Development of a new preventive strategy for mental disorders focusing on the accumulation of advanced glycation end products during prenatal and adolescent periods

• Project/Area Number: 20H03951
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 58030:Hygiene and public health-related: excluding laboratory approach
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: NISHIDA ATSUSHI 公益財団法人東京都医学総合研究所, 社会健康医学研究センター, 社会健康医学研究センター長 (20510598)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Project Status: Completed (Fiscal Year 2023)
• Budget Amount: ¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000); Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2022: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2021: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000); Fiscal Year 2020: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
• Keywords: 終末糖化産物 / 精神疾患 / 思春期 / 胎生期 / コホート / メンタルヘルス / 糖化ストレス / 環境要因 / 乳歯 / AGEｓ / 皮膚 / 予防

Outline of Research at the Start

本研究では、約4割の統合失調症患者に認められるAGEs関連代謝障害に着目し、胎生期・思春期のAGEsの蓄積が後の精神疾患の発症を予測する可能性について大規模発達コホート研究により実証的に明らかにする。脱落乳歯から胎生期のAGEs蓄積を測定する技術、および皮膚から思春期のAGEs蓄積を非侵襲・短時間で測定する技術を疫学研究に導入し、精神疾患の発症可能性の高い一群を早期に発見し、AGEsを下げうる環境要因や生活行動を同定し、精神疾患の新たな予防戦略を見出すことを目的とする。

Outline of Final Research Achievements

In this study, we focused on advanced glycation end products (AGEs)-related metabolic disfunction observed in a subgroup of patients with mental disorders. We found that the accumulation of AGEs during prenatal and adolescent periods may predict the emergence of psychotic symptoms. We also found that social stress during adolescence (experience of being bullied) and low muscle strength increase advanced glycation end products during adolescence.

Academic Significance and Societal Importance of the Research Achievements

本研究により、発達期における終末糖化産物の蓄積が精神疾患の発症を予測する可能性が示唆され、さらに終末糖化産物の蓄積リスクを高める発達期要因が複数見いだされた。こうした知見に基づき、今後、終末糖化産物の蓄積を予防することで、メンタルヘルスを増進させる効果的な介入戦略が見いだされる可能性があり、本研究の成果の社会的意義は大きいと考えらえる。

Research Products

• [Int'l Joint Research] Northwestern Feinberg School of Medicine(米国)
• [Int'l Joint Research] Northwestern Feinberg School of Medicine(米国)
• [Journal Article] Longitudinal trajectories of anterior cingulate glutamate and subclinical psychotic experiences in early adolescence: the impact of bullying victimization. (2024)
  • Author(s): N. Okada，N. Yahata，D. Koshiyama，K. Morita，K. Sawada，S. Kanata，S. Fujikawa，N. Sugimoto，R. Toriyama，M. Masaoka，S. Koike，T. Araki，Y. Kano，K. Endo，S. Yamasaki，S. Ando，A. Nishida，M. Hiraiwa-Hasegawa，R. A. E. Edden，A. Sawa and K. Kasai
  • Journal Title: Mol Psychiatry Volume: Online ahead of print Issue: 4 Pages: 939-950
  • DOI: 10.1038/s41380-023-02382-8
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Urinary exosomal microRNAs as predictive biomarkers for persistent psychotic-like experiences (2023)
  • Author(s): Tomita Y, Suzuki K, Yamasaki S, Toriumi K, Miyashita M, Ando S, Endo K, Yoshikawa A, Tabata K, Usami S, Hiraiwa-Hasegawa M, Itokawa M, Kawaji H, Kasai K, Nishida A, Arai M.
  • Journal Title: Schizophrenia Volume: 9 Issue: 1 Pages: 14-14
  • DOI: 10.1038/s41537-023-00340-5
  • Peer Reviewed / Open Access
• [Journal Article] Role of advanced glycation end products in the longitudinal association between muscular strength and psychotic symptoms among adolescents (2022)
  • Author(s): Suzuki Kazuhiro、Yamasaki Syudo、Miyashita Mitsuhiro、Ando Shuntaro、Toriumi Kazuya、Yoshikawa Akane、Nakanishi Miharu、Morimoto Yuko、et al.
  • Journal Title: Schizophrenia Volume: 8 Issue: 1 Pages: 8-8
  • DOI: 10.1038/s41537-022-00249-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Fingertip advanced glycation end products and psychotic symptoms among adolescents (2021)
  • Author(s): Miyashita Mitsuhiro, Toriumi Kazuya (5番目/23人中), et al.
  • Journal Title: npj Schizophrenia Volume: 7 Issue: 1 Pages: 37-37
  • DOI: 10.1038/s41537-021-00167-y
  • Peer Reviewed / Open Access
• [Book] 思春期のメンタルヘルス疫学：東京ティーンコホートについて (2021)
  • Author(s): 安藤俊太郎、山崎修道、西田淳志
  • Total Pages: 10
  • Publisher: 医学書院
• [Remarks] Tokyo Teen Cohort
  • URL: http://ttcp.umin.jp/
• [Remarks] 東京ティーンコホート
  • URL: http://ttcp.umin.jp/