Study on pathophysiology of schizophrenia approached from a prototype case

• Project/Area Number: 25253074
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: ITOKAWA Masanari 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, 病院等連携研究センター長 (40332324)
• Co-Investigator(Kenkyū-buntansha): 吉川 武男 国立研究開発法人理化学研究所, 脳科学総合研究センター, チームリーダー (30249958)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥44,590,000 (Direct Cost: ¥34,300,000、Indirect Cost: ¥10,290,000); Fiscal Year 2016: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000); Fiscal Year 2015: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000); Fiscal Year 2014: ¥11,310,000 (Direct Cost: ¥8,700,000、Indirect Cost: ¥2,610,000); Fiscal Year 2013: ¥12,480,000 (Direct Cost: ¥9,600,000、Indirect Cost: ¥2,880,000)
• Keywords: 異種性 / プロトタイプ / 臨床精神分子遺伝学 / 統合失調症

Outline of Final Research Achievements

Aim of our study is to clarify the pathology of schizophrenia by detecting a rare mutation with relatively large effect in a prototype case so as to extend it to general polymorphisms. We aimed to elucidate the homogeneous relative small subgroup of schizophrenia sharing a large gene effect since we investigated not based upon the CDCV hypothesis. We extended the prototype with framehift mutation of GLO1 to 40% of the general cases isolated from common cases as a relatively homogeneous pathophysiology called as carbonyl stress. We created model mice that showed deviation of turnover of neurotransmitter. Carbonyl stress was replicated in multiple hospitals.

Research Products

• [Journal Article] High-resolution copy number variation analysis of schizophrenia in Japan. (2017)
  • Author(s): Kushima I, Aleksic B, Nakatochi M, Shimamura T, Shiino T, Yoshimi A, Kimura H, Takasaki Y, Wang C, Xing J, Ishizuka K, Oya-Ito T, Nakamura Y, Arioka Y, Maeda T, Yamamoto M, Yoshida M, Noma H, Hamada S, Morikawa M, Uno Y, Okada T, Iidaka T, Iritani S, Yamamoto T,
  • Journal Title: Molecular Psychiatry Volume: 22 Issue: 3 Pages: 430-440
  • DOI: 10.1038/mp.2016.88
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The regulation of soluble receptor for AGEs contributes to carbonyl stress in schizophrenia. (2016)
  • Author(s): Miyashita M, Watanabe T, Ichikawa T, Toriumi K, Horiuchi Y, Kobori A, Kushima I, Hashimoto R, Fukumoto M, Koike S, Ujike H, Arinami T, Tatebayashi Y, Kasai K, Takeda M, Ozaki N, Okazaki Y, Yoshikawa T, Amano N, Washizuka S, Yamamoto H, Miyata T, Itokawa M, Yamamoto Y, Arai M.
  • Journal Title: Biochem Biophys Res Commun. Volume: 479 Pages: 447-452
  • Peer Reviewed / Open Access
• [Journal Article] A method for estimating spatial resolution of real image in the Fourier domain. (2016)
  • Author(s): Mizutani R, Saiga R, Takekoshi S, Inomoto C, Nakamura N, Itokawa M et al.
  • Journal Title: J Microsc. Volume: 261 Issue: 1 Pages: 57-66
  • DOI: 10.1111/jmi.12315
  • Peer Reviewed
• [Journal Article] The piccolo intronic single nucleotide polymorphism rs13438494 regulates dopamine and serotonin uptake and shows associations with dependence-like behavior in genomic association study. (2015)
  • Author(s): Uno K, Nishizawa D, Seo S, Takayama K, Matsumura S, Sakai N, Ohi K, Nabeshima T, Hashimoto R, Ozaki N, Hasegawa J, Sato N, Tanioka F, Sugimura H, Fukuda K, Higuchi S, Ujike H, Inada T, Iwata N, Sora I, Iyo M, Kondo N, Won M-J, Naruse N, Uehara K, Itokawa M, Yamada M, Ikeda K, Miyamoto Y, Nitta A.
  • Journal Title: Current molecular medicine Volume: 15(3) Issue: 3 Pages: 265-274
  • DOI: 10.2174/1566524015666150330145722
  • Peer Reviewed
• [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] Associations between the orexin (hypocretin) receptor 2 gene polymorphism Val308Ile and nicotine dependence in genome-wide and subsequent association studies. (2015)
  • Author(s): Nishizawa D et al.
  • Journal Title: Mol Brain. Volume: 8 Issue: 1 Pages: 50-50
  • DOI: 10.1186/s13041-015-0142-x
  • Peer Reviewed / Open Access
• [Journal Article] Three-Dimensional Neuronal Structure of Human Cerebral Cortex Determined by Synchrotron-Radiation Microtomography. (2015)
  • Author(s): Saiga R, Takekoshi S, Inomoto C, Nakamura N, Tsuboi A, Osawa M, Arai M, Oshima K, Itokawa M, Uesugi K, Takeuchi A, Terada Y, Suzuki Y and Mizutani R.
  • Journal Title: Microsc. Microanal Volume: 21 Issue: S3 Pages: 919-920
  • DOI: 10.1017/s1431927615005395
  • Peer Reviewed / Open Access
• [Journal Article] 脳と心-分子生物学は精神疾患を解明するのか- (2015)
  • Author(s): 糸川昌成
  • Journal Title: 科学哲学 Volume: 47-2 Pages: 53-68
  • NAID: 130005089339
  • Peer Reviewed
• [Journal Article] Genetic analysis of the glyoxalase system in schizophrenia. (2015)
  • Author(s): Bangel FN, Yamada K, Arai M, Iwayama Y, Balan S, Toyota T, Iwata Y, Suzuki K, Kikuchi M, Hashimoto T, Kanahara N, Mori N, Itokawa M, Stork O, Yoshikawa T
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry Volume: 59 Pages: 105-110
  • DOI: 10.1016/j.pnpbp.2015.01.014
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Utility of Scalp Hair Follicles as a Novel Source of Biomarker Genes for Psychiatric Illnesses. (2014)
  • Author(s): Maekawa M, Yamada K, Toyoshima M, Ohnishi T, Iwayama Y, Shimamoto C, Toyota T, Nozaki Y, Balan S, Matsuzaki H, Iwata Y, Suzuki K, Miyashita M, Kikuchi M, Kato M, Okada Y, Akamatsu W, Mori N, Owada Y, Itokawa M, Okano H, Yoshikawa T.
  • Journal Title: Biological Psychiatry Volume: 3223 Issue: 2 Pages: 00570-00578
  • DOI: 10.1016/j.biopsych.2014.07.025
  • NAID: 40020643113
  • Peer Reviewed / Open Access
• [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] 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] 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] Measurement of glyoxalase activities (2014)
  • Author(s): Arai M, Nihonmatsu-Kikuchi N, Itokawa M, Rabbani N, Thornally PJ
  • Journal Title: Biochem Soc Trans Volume: 42(2) Issue: 2 Pages: 491-492
  • DOI: 10.1042/bst20140010
  • 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－ (2014)
  • 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: 25(3) Pages: 254-261
  • NAID: 130006832757
  • 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] Biodosimetry of Restoration Workers for The Tokyo Electric Power Company (TEPCO) Fukushima Daiichi Nuclear Power Station Accident (2013)
  • Author(s): Suto Y, Hirai M, Akiyama M, Kobashi G, Itokawa M, Akashi M, Sugiura N
  • Journal Title: Health Phys Volume: 105(4) Issue: 4 Pages: 366-373
  • DOI: 10.1097/hp.0b013e3182995e42
  • Peer Reviewed
• [Journal Article] Volume reductions in frontopolar and left perisylvian cortices inmethamphetamine induced psychosis (2013)
  • Author(s): Aoki Y, Orikabe L, Takayanagi Y, Yahata N, Mozue Y, Sudo Y, Ishii T, Itokawa M, Suzuki M, Kurachi M, Okazaki Y, Kasai K, Yamasue H
  • Journal Title: Schizophr Res Volume: 147(2-3) Pages: 355-361
  • Peer Reviewed
• [Presentation] 心はどこへつながるのか -分子生物学からポリネシアまで- (2017)
  • Author(s): 糸川昌成
  • Organizer: 第12回日本統合失調症学会
  • Place of Presentation: 米子コンベンションセンター（鳥取県米子市）
  • Year and Date: 2017-03-23
  • Invited
• [Presentation] カルボニルストレス関連分子による統合失調症バイオマーカーの探索 (2017)
  • Author(s): 糸川昌成
  • Organizer: 脳とこころの研究第二回公開シンポジウム「脳を考える」
  • Place of Presentation: イイノホール(東京都千代田区）
• [Presentation] 精神症状はどこから生まれるのか‐精神疾患の治療薬開発が難航する理由-. (2016)
  • Author(s): 糸川昌成
  • Organizer: 第46回日本神経精神薬理学会
  • Place of Presentation: COEX, 韓国ソウル
  • Year and Date: 2016-07-02
  • Invited
• [Presentation] 当事者に望まれる最適な支援～自分らしく笑顔で生きるために～ (2016)
  • Author(s): 糸川昌成
  • Organizer: 第11回日本統合失調症学会
  • Place of Presentation: ベイシア文化ホール（群馬県前橋市）
  • Year and Date: 2016-03-26
  • Invited
• [Presentation] 設計図より大工の腕‐遺伝子研究からみたリカバリー (2016)
  • Author(s): 糸川昌成
  • Organizer: 第11回日本統合失調症学会
  • Place of Presentation: ベイシア文化ホール（群馬県前橋市）
  • Year and Date: 2016-03-26
  • Invited
• [Presentation] 脳とこころ (2016)
  • Author(s): 糸川昌成
  • Organizer: 第14回日本ヨーガ療法学会研究総会分科会
  • Place of Presentation: 大宮ソニックシティー国際会議室（埼玉県さいたま市大宮区）
  • Invited
• [Presentation] 統合失調症治療薬に関する医師主導治験 (2015)
  • Author(s): 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シンポジウム
  • Place of Presentation: タワーホール船堀（東京都江戸川区）
  • Year and Date: 2015-09-24
  • Invited
• [Presentation] 統合失調症の病態研究－症候群から疾患を抽出するこころみ－ (2015)
  • Author(s): 糸川昌成
  • Organizer: 九州大学先端融合医療レドックスナビ研究拠点若手研究者主催シンポジウム
  • Place of Presentation: 九州大学（福岡県福岡市）
  • Year and Date: 2015-01-27
  • Invited
• [Presentation] 酸化ストレス・炎症と精神疾患 (2014)
  • Author(s): 糸川昌成
  • Organizer: 第36回日本生物学的精神医学会
  • Place of Presentation: 奈良県文化会館（奈良県奈良市）
  • Year and Date: 2014-10-29
  • Invited
• [Presentation] 希少症例を出発点とする統合失調症の病態研究と治療法の開発－異業種と複雑系－ (2014)
  • Author(s): 糸川昌成
  • Organizer: 第110回日本精神神経学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-06-27
  • Invited
• [Presentation] 統合失調症の認知機能障害とカルボニルストレスの関連についての予備的検討
  • Author(s): 小堀晶子, 宮下光弘, 市川智恵 鳥海和也, 新井誠, 新井平伊, 糸川昌成.
  • Organizer: 第9回日本統合失調症学会
  • Place of Presentation: 京都
• [Presentation] 疾患由来iPS細胞を用いたカルボニルストレス性統合失調症の病因解明
  • Author(s): 豊島学, 岡田洋平, 赤松和士, 糸川昌成, 岡野栄之, 吉川武男
  • Organizer: 第9回日本統合失調症学会
  • Place of Presentation: 京都
• [Presentation] 統合失調症患者の染色体転座切断点に同定した遺伝子DISC-Mの機能解析
  • Author(s): 糸川昌成, 市川智恵, 新井誠, 宮下光弘, 鳥海和也, 小堀晶子
  • Organizer: 第46回精神神経系薬物治療研究報告会
  • Place of Presentation: 豊中
• [Presentation] Research on carbonyl stress as pathophysiology of schizophrenia
  • Author(s): Itokawa M, Arai M, Miyashita M, Miyata T
  • Organizer: Glyoxalase Centennial:100 Years of Glyoxalase Research and Emergence of Dicarbonyl Stress
  • Place of Presentation: Coventry, UK
• [Presentation] Cytogenetic Analysis of Restoration Workers for Fukushima Daiichi Nuclear Power Station Accident
  • Author(s): Suto Y, Itokawa M
  • Organizer: MELODI 2013
  • Place of Presentation: Brussels
• [Presentation] Research on pathophysiology of schizophrenia; evidence revealed by molecular biological studies reorganizing classification of mental disorders
  • Author(s): Itokawa M
  • Organizer: Tokyo Conference on Philosophy of Psychiatry
  • Place of Presentation: Tokyo
• [Presentation] カルボニルストレス性統合失調症の研究
  • Author(s): 11. 糸川昌成, 新井誠, 宮下光弘, 市川智恵, 鳥海和也, 小堀晶子, 宮田敏男
  • Organizer: Neuro 2013
  • Place of Presentation: 京都
• [Book] 精神医学の科学と哲学 (2016)
  • Author(s): 石原孝二, 信原幸弘, 糸川昌成
  • Total Pages: 240
  • Publisher: 東京大学出版会
• [Book] 科学者が脳と心をつなぐとき～父と母と私が織りなす50年の物語～ (2016)
  • Author(s): 糸川昌成
  • Total Pages: 135
  • Publisher: 地域精神保健福祉機構
• [Book] 統合失調症が秘密の扉をあけるまで (2014)
  • Author(s): 糸川昌成
  • Total Pages: 132
  • Publisher: 星和書店
• [Remarks] 統合失調症プロジェクト
  • URL: http://www.igakuken.or.jp/schizo-dep/
• [Remarks] 統合失調症の原因究明と予防法・治療法の開発
  • URL: http://www.igakuken.or.jp/schizo-dep/
• [Patent(Industrial Property Rights)] 統合失調症の検査および治療 (2013)
  • Inventor(s): 糸川昌成、宮田敏男、新井誠
  • Industrial Property Rights Holder: 糸川昌成、宮田敏男、新井誠
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-05-22
  • Acquisition Date: 2013-06-14