Investigation to elucidate the pathophysiology of schizophrenia using carbonyl stress biomarkers

• Project/Area Number: 25861040
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Psychiatric science
• Research Institution: Tokyo Metropolitan Institute of Medical Science (2015); Shinshu University (2013-2014)
• Principal Investigator: MIYASHITA Mitsuhiro 公益財団法人東京都医学総合研究所, 精神行動医学研究分野, 主席研究員 (60532132)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: カルボニルストレス / 統合失調症 / ペントシジン / ビタミンB6 / 終末糖化産物

Outline of Final Research Achievements

We investigated reproducibility of enhanced carbonyl stress in another new larger cohort of schizophrenic patients. As a result of the investigation, we found significant increase of pentosidine levels and decrease of serum pyridoxal in schizophrenia, respectively when compared to those of control subjects. In addition, we found that patients with enhanced carbonyl stress shared many clinical features with treatment-resistant schizophrenia. These include a higher proportion of inpatients, longer durations of hospitalization, and higher doses of antipsychotic medication, compared with patients without carbonyl stress. Interestingly, psychopathological symptoms showed a tendency towards negative association with serum vitamin B6 levels. Our results support the idea that treatment regimes reducing carbonyl stress, such as supplementation of pyridoxamine, could provide novel therapeutic benefits for this subgroup of patients.

Research Products

• [Journal Article] Characterization of modified proteins in plasma from a subtype of schizophrenia based on carbonyl stress: Protein carbonyl is a possible biomarker of psychiatric disorders. (2015)
  • Author(s): Koike S, Kayama T, Arai M, Horiuchi Y, Kobori A, Miyashita M, Itokawa M, Ogasawara Y.
  • Journal Title: Biochem Biophys Res Commun. Volume: 467 Issue: 2 Pages: 361-366
  • DOI: 10.1016/j.bbrc.2015.09.152
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Advanced glycation end products and schizophrenia: A systematic review. (2015)
  • Author(s): Kouidrat Y, Amad A, Arai M, Miyashita M, Lalau JD, Loas G, Itokawa M.
  • Journal Title: J Psychiatr Res. Volume: 66-67 Pages: 112-117
  • DOI: 10.1016/j.jpsychires.2015.04.023
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] カルボニルストレス代謝障害と統合失調症 (2015)
  • Author(s): 新井誠、小堀晶子、宮下光弘、鳥海和也、堀内泰江、畠山幸子、内田美樹、井上智子、糸川昌成
  • Journal Title: 日本生物学的精神医学会誌 Volume: 26(1) Pages: 27-33
  • NAID: 130005395573
• [Journal Article] Carbonyl stress inschizophrenia (2014)
  • Author(s): Itokawa M, Miyashita M, Arai M, Miyata T
  • Journal Title: Biochem Soc Trans Volume: 42(2) Issue: 2 Pages: 468-72
  • DOI: 10.1042/bst20140044
  • Peer Reviewed
• [Journal Article] Carbonyl stress and schizophrenia (2014)
  • Author(s): Makoto Aarai, Mitsuhiro Miyashita, Akiko Kobori, Kazuya Toriumi, Yasue Hoiuchi, and Masanari Itokawa
  • Journal Title: Psychiatry and Clinical Neuroscience 2014 Volume: 68 Issue: 9 Pages: 655-665
  • DOI: 10.1111/pcn.12216
  • Peer Reviewed
• [Journal Article] Replication of enhanced carbonyl stress in a subpopulation of schizophrenia (2014)
  • Author(s): Miyashita M, Arai M, Yuzawa H, Niizato K, Oshima K, Kushima I, Hashimoto R, Fukumoto M, Koike S, Toyota T, Ujike H, Arinami T, Kasai K, Takeda M, Ozaki N, Okazaki Y, Yoshikawa T, Amano N, Miyata T, Itokawa M
  • Journal Title: Psychiatry Clin Neurosci Volume: 68 Issue: 1 Pages: 83-84
  • DOI: 10.1111/pcn.12081
  • Peer Reviewed
• [Journal Article] Clinical features of schizophrenia with enhanced carbonyl stress (2014)
  • Author(s): Miyashita M, Arai M, Kobori A, Ichikawa T, Toriumi K, Niizato K, Oshima, K, Okazaki Y, Yoshikawa T, Amano N, Miyata T, Itokawa M.
  • Journal Title: Schizophr Bull. Volume: 40（５） Issue: 5 Pages: 1040-1046
  • DOI: 10.1093/schbul/sbt129
  • Peer Reviewed
• [Journal Article] カルボニルストレスという代謝異常と統合失調症：体に負担の少ないビタミンB6による治療法の研究 (2013)
  • Author(s): 宮下光弘、新井誠、市川智恵、鳥海和也、小堀晶子、天野直二、糸川昌成
  • Journal Title: 総合病院精神医学 Volume: 第25巻 (3) Pages: 254-261
  • NAID: 130006832757
  • Peer Reviewed
• [Presentation] Pentosidene accumulation in the pathophysiology of Schizophrenia (2015)
  • Author(s): M Arai, Y Horiuchi, A Kobori, M Miyashita, K Toriumi, S Hashimoto, M Itokawa
  • Organizer: Society for Neuroscience 45th Annual Meeting
  • Place of Presentation: Chicago, USA
  • Year and Date: 2015-10-21
  • Int'l Joint Research
• [Presentation] 神経炎症・酸化ストレスをキーワードにした精神疾患の理解：糖化・酸化ストレスと関連する統合失調症の病態研究 (2015)
  • Author(s): 新井誠. 堀内泰江、小堀晶子、鳥海和也、畠山幸子、宮下光弘、糸川昌成
  • 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: タワーホール船堀（東京都・江戸川区）
  • Year and Date: 2015-09-24
• [Presentation] Clinical features of schizophrenia with enhanced carbonyl stress and potential therapeutic value of vitamin B6 (2015)
  • Author(s): Mitsuhiro Miyashita, Makoto Arai, Akiko Kobori, Yasue Horiuchi, Kazuya Toriumi, Tomoe Ichikawa, Kazuhiro Niizato, Kenichi Oshima, Yuji Okazaki, Takeo Yoshikawa, Naoji Amano, Toshio Miyata, Masanari Itokawa.
  • Organizer: 第10回日本統合失調症学会
  • Place of Presentation: 東京 都市センターホテル, 東京都千代田区平河町2-4-1
  • Year and Date: 2015-03-27 – 2015-03-28
• [Presentation] カルボニルストレスを呈する統合失調症の臨床特徴 (2013)
  • Author(s): 宮下光弘、新井 誠、小堀 晶子、市川 智恵、鳥海 和也、新井 麻友美、小幡 菜々子、野原 泉、大島 健一、新里 和弘、岡崎 祐士、吉川 武男、天野 直二、糸川 昌成
  • Organizer: 第8回統合失調症学会
  • Place of Presentation: 浦河、北海道
• [Presentation] カルボニルストレス性統合失調症の臨床特徴 (2013)
  • Author(s): 宮下 光弘、新井 誠、市川 智恵、鳥海 和也、小堀 晶子、新井 麻友美、小幡 菜々子、岡崎 祐士、吉川 武男、天野 直二、糸川 昌成
  • Organizer: 第109回日本精神神経学会
  • Place of Presentation: 福岡
• [Presentation] Clinical features of schizophrenia with enhanced carbonyl stress (2013)
  • Author(s): Mitsuhiro Miyashita, Makoto Araia, Akiko Koboria, Tomoe Ichikawaa, Kazuya Toriumia, Hiroko Yuzawab, Izumi Noharaa, Mayumi Araia, Nanako Obataa, Yuji Okazakic, Takeo Yoshikawad, Naoji Amanoe, Masanari Itokawa
  • Organizer: 第11回世界生物学的精神医学会
  • Place of Presentation: 京都
• [Book] 「メンタル医療～原因解明と診断、治療の最前線～」 (2013)
  • Author(s): 宮下光弘、新井誠、市川智恵、鳥海和也、小堀晶子、天野直二、糸川昌成
  • Total Pages: 200
  • Publisher: シーエムシー出版