Postmortem brain study of development-dependently expressed genes in mental disorders focusing on onset age

• Project/Area Number: 25860991
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Psychiatric science
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Uezato Akihito 東京医科歯科大学, 医歯(薬)学総合研究科, 助教 (90547449)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 死後脳 / 遺伝子 / 精神疾患 / 遺伝子発現 / 発達依存性

Outline of Final Research Achievements

In mental diseases with post-adolescent onset, a dysfunction of neural circuits that mature during adolescence or alterations of the related molecules and genes are speculated. We found the expression of synapse-associated protein 97 (SAP97) increased only after a developmental critical period in response to NMDA receptor blocker administration, therefore, SAP97 gene was regarded as development-dependent risk gene of schizophrenia. The mRNA expression analysis of SAP97 new splicing variant in postmortem brains of schizophrenia revealed the reduced expression in early-onset schizophrenia, indicating its involvement in the disease development process.

Research Products

• [Journal Article] Changes in cortical N-methyl-d-aspartate receptors and post-synaptic density protein 95 in schizophrenia, mood disorders and suicide (2016)
  • Author(s): Dean, B. et al.
  • Journal Title: Aust N Z J Psychiatry Volume: 50 Pages: 275-283
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Reduced cortical expression of a newly identified splicing variant of the DLG1 gene in patients with early-onset schizophrenia (2015)
  • Author(s): Uezato, A. et al.
  • Journal Title: Transl Psychiatry Volume: 5
  • Peer Reviewed
• [Journal Article] 統合失調症のグルタミン酸仮説と診断の可能性 (2015)
  • Author(s): 上里彰仁、山本直樹、西川徹
  • Journal Title: 精神科治療学 Volume: 30 Pages: 11-17
• [Journal Article] グルタミン酸仮説における治療抵抗性と今後の展望 (2014)
  • Author(s): 上里彰仁、山本直樹、西川徹
  • Journal Title: 臨床精神薬理 Volume: 17 Pages: 1625-1630
• [Journal Article] Molecular pathology of schizophrenia (2013)
  • Author(s): Akihito Uezato, Toru Nishikawa
  • Journal Title: Nihon Rinsho Volume: 71 Pages: 591-598
  • NAID: 40019630248
• [Presentation] 精神疾患における死後脳および遺伝子研究 (2014)
  • Author(s): 上里彰仁
  • Organizer: 日本生物学的精神医学会将来計画委員会企画・第三回若手研究者育成プログラム
  • Place of Presentation: 奈良
  • Year and Date: 2014-09-29 – 2014-10-01
  • Invited
• [Presentation] Identification of developmentally-regulated phencyclidine-inducible gene and its genetic association with schizophrenia (2013)
  • Author(s): Uezato, Akihito Kimura-Sato, Junko Hiraoka, Shuichi Yamamoto, Naoki Kajii, Yasushi Kuroda, Yasukazu Umino, Asami Iijima, Yoshimi Kunugi, Hiroshi Nishikawa, Toru
  • Organizer: 11th World Congress of Biological Psychiatry
  • Place of Presentation: Kyoto