Elucidation of the etiology of and overcoming schizophrenia by applying the investigation of patients with schizophrenia whose L-serine synthesis pathway is disturbed

• Project/Area Number: 25461740
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Dokkyo Medical University
• Principal Investigator: Ozeki Yuji 獨協医科大学, 医学部, 准教授 (90303768)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 統合失調症 / L-セリン / D-セリン / ホスホセリンホスファターゼ / ホスホセリンアミノトランスフェラーゼ / ホスホグリセリン酸デヒドロゲナーゼ / グリシン

Outline of Final Research Achievements

The treatment for schizophrenia has improved, but there are some symptoms which do not improve entirely. The cause of illness remains being unexplained. If the etiology of schizophrenia is elucidated, a treatment and the prophylaxis of schizophrenia will progress. There are various hypotheses, but we hypothesized that the L-serine synthesis pathway might be related with a disease, so we investigated the L-serine synthesis pathway system in the patients. As a result, we found synthetic ability of the synthetases of L-serine increasing in the patients. In addition, we found that quantities of the mRNA expression of the enzymes which synthesize L-serine were decreased in the patients. However, as a whole, the association between such change and blood concentration of L-serine was not found. In future, we are going to investigate the relationship between L-serine synthesis pathway and the blood concentration of L-serine or amino acids related to L-serine.

Research Products

• [Journal Article] Phosphoserine phosphatase activity is elevated and correlates negatively with plasma d-serine concentration in patients with schizophrenia. (2016)
  • Author(s): Yuji Ozeki, Masae Sekine, Kumiko Fujii, Takashi Watanabe, Hiroaki Okayasu, Yumiko Takano, Takahiro Shinozaki, Akiko Aoki, Kazufumi Akiyama, Hiroshi Homma, Kazutaka Shimoda
  • Journal Title: Psychiatry Research Volume: 237 Pages: 344-350
  • DOI: 10.1016/j.psychres.2016.01.010
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Plasma concentrations of three methylated arginines,endogenous nitric oxide synthase inhibitors, in schizophrenic patients undergoing antipsychotic drug treatment (2016)
  • Author(s): Satoko Nonaka-Hashida, Masae Sekine, Yuji Ozeki , Kumiko Fujii, Kazufumi Akiyama, Kazutaka Shimoda, Makoto Tsunoda, Masumi Katane, Yasuaki Saitoh, Tetsuya Miyamoto, Hiroshi Homma
  • Journal Title: Psychiatry Research Volume: 238 Pages: 203-210
  • DOI: 10.1016/j.psychres.2016.02.029
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Attitudes toward metabolic adverse events among patients with schizophrenia in Japan. (2016)
  • Author(s): Norio Sugawara, Nrio Yasui-Furukori, Mnabu Yamazaki, Kazutaka Shimoda, Takao Mori, Takuro Sugai, Hiroshi Matsuda, Yutaro Suzuki, Yoshitake Minami, Yuji Ozeki, Kurefu Okamoto, Toyoaki Sagae, Toshiyuki Someya.
  • Journal Title: Neuropsychiatric Disease and Treatment Volume: 12 Pages: 427-36
  • DOI: 10.2147/ndt.s98711
  • Peer Reviewed / Open Access
• [Journal Article] Difference in prevalence of metabolic syndrome between Japanese outpatients and inpatients with schizophrenia: A nationwide survey (2016)
  • Author(s): Sugai T, Suzuki Y, Yamazaki M, Shimoda K, Mori T, Ozeki Y, Matsuda H, Sugawara N, Yasui-Furukori N, Minami Y, Okamoto K, Sagae T, Someya T
  • Journal Title: Schizophrenia research Volume: 171（1－3） Issue: 1-3 Pages: 68-73
  • DOI: 10.1016/j.schres.2016.01.016
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] High prevalence of underweight and undernutrition in Japanese inpatients with schizophrenia: a nationwide survey (2015)
  • Author(s): Takuro Sugai, Yutaro Suzuki, Manabu Yamazaki, Kazutaka Shimoda, Takao Mori, Yuji Ozeki, Hiroshi Matsuda, Norio Sugawara, Norio Yasui-Furukori, Yoshitake Minami, Kurefu Okamoto, Toyoaki Sagae, Toshiyuki Someya.
  • Journal Title: BMJ Open. Volume: 5 Issue: 12 Pages: e008720-e008720
  • DOI: 10.1136/bmjopen-2015-008720
  • Peer Reviewed / Open Access
• [Journal Article] QT is Longer in Drug-Free Patients with Schizophrenia Compared with Age-Matched Healthy Subjects. (2014)
  • Author(s): Kumiko Fujii, Yuji Ozeki, Hiroaki Okayasu, Yumiko Takano, Takahiro Shinozaki, Hiroaki Hori, Masami Orui, Minoru Horie, Hiroshi Kunugi, Kazutaka Shimoda
  • Journal Title: PLOS ONE Volume: 9(6) Issue: 6 Pages: e98555-e98555
  • DOI: 10.1371/journal.pone.0098555
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Development of acute pancreatitis caused by sodium valproate in a patient with bipolar disorder on hemodialysis for chronic renal failure: a case report (2014)
  • Author(s): Hiroaki Okayasu, Takahiro Shinozaki, Akira Osone, Yuji Ozeki and Kazutaka Shimoda
  • Journal Title: BMC Psychiatry Volume: 14 Issue: 1 Pages: 93-93
  • DOI: 10.1186/1471-244x-14-93
  • Peer Reviewed
• [Journal Article] An association study of the Hermansky-Pudlak syndrome type 4 gene in schizophrenic patients (2013)
  • Author(s): Saito A, Kuratomi G, Ito C, Matsuoka H, Suzuki T, Ozeki Y, Watanabe T, Fujii K, Shimoda K, Fukushima Y, Inukai T, Ohmori K, Akiyama K.
  • Journal Title: Psychiatr Genet Volume: 23(4) Issue: 4 Pages: 163-73
  • DOI: 10.1097/ypg.0b013e32836130a9
  • Peer Reviewed
• [Journal Article] Kazutaka Shimoda Pharmachotherapeutic determinants for QTc interval prolongation in Japanese patients with mood disorder (2012)
  • Author(s): Hiroaki Okayasu, Yuji Ozeki, Kumiko Fujii, Yumiko Takano, Yoshinori Saeki, Hiroaki Hori, Minoru Horie, Teruhiko Higuchi, Hiroshi Kunugi
  • Journal Title: Pharmacopsychiatry Volume: (in press) Issue: 07 Pages: 279-83
  • DOI: 10.1055/s-0032-1308969
  • Peer Reviewed
• [Presentation] 統合失調症における末梢各種アミノ酸濃度と診断との関連 および各種アミノ酸相互作用の共分散構造分析を用いた解析 (2016)
  • Author(s): 尾関祐二、藤井久彌子、関根正恵、渡邊崇、髙野有美子、岡安寛明、篠崎隆央、青木顕子、青木秀明、森玄房、秋山一文、本間浩、下田和孝
  • Organizer: 第11回 日本統合失調症学会
  • Place of Presentation: 前橋 群馬
  • Year and Date: 2016-03-25
• [Presentation] 統合失調症におけるグルタミン酸-グルタミンサイクル関連アミノ酸の共分散構造分析による相互作用の解析 (2015)
  • Author(s): 尾関祐二、藤井久彌子、関根正恵、渡邊崇、髙野有美子、岡安寛明、篠崎隆央、青木顕子、青木秀明、森玄房、秋山一文、本間浩、下田和孝
  • Organizer: 第45回日本神経精神薬理学会第37回日本生物学的精神医学会合同年会
  • Place of Presentation: 東京
  • Year and Date: 2015-09-24
• [Presentation] Phosphoserine phosphatase activity is elevated and negatively correlated with plasma D-serine concentration in schizophrenia patients (2015)
  • Author(s): Yuji Ozeki, Masae Sekine, Kumiko Fujii, Takashi Watanabe, Hiroaki Okayasu, Yumiko Takano, Takahiro Shinozaki, Akiko Aoki, Hideaki Aoki, Harunobu Mori, Kazufumi Akiyama, Hiroshi Homma, Kazutaka Shimoda
  • Organizer: International Congress on Schizophrenia Research
  • Place of Presentation: Colorado Springs, Colorado, USA
  • Year and Date: 2015-04-01
  • Int'l Joint Research
• [Presentation] Phosphoserine phosphatase activity is elevated and negatively correlated with plasma D-serine concentration in schizophrenia patients (2015)
  • Author(s): Yuji Ozeki
  • Organizer: 15th International Congress on Schizophrenia Research
  • Place of Presentation: Colorado Springs, Colorado, USA
  • Year and Date: 2015-03-28 – 2015-04-01
• [Presentation] 向精神薬による循環器への影響 特に心室性不整脈の観点から (2014)
  • Author(s): 尾関祐二、藤井久彌子、髙野有美子、岡安寛明、篠崎隆央、下田和孝
  • Organizer: 第24回日本臨床精神神経薬理学会、第44回日本臨床精神神経薬理学会合同年会
  • Place of Presentation: 名古屋
  • Year and Date: 2014-11-20 – 2014-11-22
  • Invited
• [Presentation] 向精神薬による循環器への影響 特に心室性不整脈の観点から (2014)
  • Author(s): 尾関祐二、藤井久彌子、髙野有美子、岡安寛明、篠崎隆央、下田和孝
  • Organizer: 第3回日本精神科医学会
  • Place of Presentation: 名古屋
  • Year and Date: 2014-10-09 – 2014-10-10
  • Invited
• [Presentation] 統合失調症患者におけるL-セリン合成能の検討 (2014)
  • Author(s): 藤井久彌子,尾関祐二、関根正恵、渡邊崇、髙野有美子、岡安寛明、篠崎隆央、青木顕子、青木秀明、森玄房、秋山一文、本間浩、下田和孝
  • Organizer: 第9回日本統合失調症学会
  • Place of Presentation: 京都
• [Presentation] Evaluation of QTc intervals in drug- naïve patients with schizophrenia (2013)
  • Author(s): Kumiko Fujii, Yuji Ozeki, Hiroaki Okayasu, Yumiko Okuri, Hiroaki Hori, Masami Orui, Minoru Horie, Hiroshi Kunugi, Kazutaka Shimoda
  • Organizer: 14th International Congress on Schizophrenia Research
  • Place of Presentation: 米国