Endophenotypes and functional analysis of schizophrenia risk gene TCF4

• Project/Area Number: 25861002
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Psychiatric science
• Research Institution: Osaka University
• Principal Investigator: FUJIMOTO Michiko 大阪大学, 医学部附属病院, 医員 (50647625)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 統合失調症 / 中間表現型 / 遺伝子多型 / 遺伝子解析 / 生物学的精神医学 / 精神神経学 / 神経科学 / ゲノム / 後部帯状回灰白質体積 / TCF4遺伝子

Outline of Final Research Achievements

Transcription factor 4 (TCF4) gene polymorphism is reported to be associated with the human brain function in the genome-wide association study (GWAS). The previous paper showed that the TCF4 polymorphism rs2958182 was related with schizophrenia in Han Chinese. Since rs2958182 is also a common polymorphism in Japanese, we performed the association study between TCF4 and schizophrenia in Japanese population. In our study, the patients with the risk allele T of rs2958182 showed low Novelty Seeking in the Temperament and Character Inventory, a self-administered questionnaire. We also found the gray matter volume of the posterior cingulum was smaller in the patients with the risk allele T of rs2958182 than that in the patients without risk allele T.

Research Products

• [Journal Article] An integrated eye movement score as a neurophysiological marker of schizophrenia (2014)
  • Author(s): Miura K, Hashimoto R, Fujimoto M, Yamamori H, Yasuda Y, Ohi K, Umeda-Yano S, Fukunaga M, Iwase M, Takeda M
  • Journal Title: Schizophrenia Research Volume: 160(1-3) Issue: 1-3 Pages: 228-9
  • DOI: 10.1016/j.schres.2014.10.023
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Common variants at 1p36 are associated with superior frontal gyrus volume. (2014)
  • Author(s): Hashimoto R, Ikeda M, Yamashita F, Ohi K, Yamamori H, Yasuda Y, Fujimoto M, Fukunaga M, Nemoto K, Takahashi T, Tochigi M, Onitsuka T, Yamasue H, Matsuo K, Iidaka T, Iwata N, Suzuki M, Takeda M, Kasai K, Ozaki N
  • Journal Title: Translational Psychiatry Volume: 4 Issue: 10 Pages: e472-e472
  • DOI: 10.1038/tp.2014.110
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Changes in plasma D-serine, L-serine, and glycine levels in treatment-resistant schizophrenia before and after clozapine treatment. (2014)
  • Author(s): Yamamori H, Hashimoto R, Fujita Y, Numata S, Yasuda Y, Fujimoto M, Ohi K, Umeda-Yano S, Ito A, Ohmori T, Hashimoto K, Takeda M.
  • Journal Title: Neurosci Lett. Volume: 582 Pages: 93-8
  • DOI: 10.1016/j.neulet.2014.08.052
  • Peer Reviewed
• [Journal Article] Duplication of the NPHP1 gene in patients with autism spectrum disorder and normal intellectual ability: a case series. (2014)
  • Author(s): Yasuda Y, Hashimoto R, Fukai R, Okamoto N, Hiraki Y, Yamamori H, Fujimoto M, Ohi K, Taniike M, Mohri I, Nakashima M, Tsurusaki Y, Saitsu H, Matsumoto N, Miyake N, Takeda M.
  • Journal Title: Ann Gen Psychiatry. Volume: 13 Issue: 1 Pages: 22-26
  • DOI: 10.1186/s12991-014-0022-2
  • Peer Reviewed / Open Access
• [Journal Article] Neuromelanin magnetic resonance imaging reveals increased dopaminergic neuron activity in the substantia nigra of patients with schizophrenia. (2014)
  • Author(s): Watanabe Y, Tanaka H, Tsukabe A, Kunitomi Y, Nishizawa M, Hashimoto R, Yamamori H, Fujimoto M, Fukunaga M, Tomiyama N.
  • Journal Title: PLoS One Volume: 9 Issue: 8 Pages: e104619-e104619
  • DOI: 10.1371/journal.pone.0104619
  • Peer Reviewed / Open Access
• [Journal Article] Performance on the Wechsler Adult Intelligence Scale-III in Japanese patients with schizophrenia. (2014)
  • Author(s): Fujino H, Sumiyoshi C, Sumiyoshi T, Yasuda Y, Yamamori H, Ohi K, Fujimoto M, Umeda-Yano S, Higuchi A, Hibi Y, Matsuura Y, Hashimoto R, Takeda M, Imura O.
  • Journal Title: Psychiatry Clin Neurosci. Volume: in press Issue: 7 Pages: 534-541
  • DOI: 10.1111/pcn.12165
  • Peer Reviewed
• [Journal Article] Cognitive inflexibility in Japanese adolescents and adults with autism spectrum disorders. (2014)
  • Author(s): Yasuda Y, Hashimoto R, Ohi K, Yamamori H, Fujimoto M, Umeda-Yano S, Fujino H, Takeda M.
  • Journal Title: World J Psychiatry. Volume: 22 Issue: 2 Pages: 42-8
  • DOI: 10.5498/wjp.v4.i2.42
  • Peer Reviewed / Open Access
• [Journal Article] Association between genetic polymorphism rs2952768, close to the METTL21A and CREB1 genes, and intellectual ability in healthy subjects (2014)
  • Author(s): Nishizawa D, Ohi K, Hashimoto R, Yamamori H, Yasuda Y, Fujimoto M, Umeda-Yano S, Takeda M, Ikeda K
  • Journal Title: Journal of Addiction Research & Therapy Volume: 5(2) Issue: 02 Pages: 1000178-1000178
  • DOI: 10.4172/2155-6105.1000178
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Genetic risk variants of schizophrenia associated with left superior temporal gyrus volume. (2014)
  • Author(s): Ohi K, Hashimoto R, Ikeda M, Yamashita F, Fukunaga M, Nemoto K, Ohnishi T, Yamamori H, Yasuda Y, Fujimoto M, Umeda-Yano S, Watanabe Y, Iwata N, Weinberger DR, Takeda M.
  • Journal Title: Cortex Volume: 58 Pages: 23-6
  • DOI: 10.1016/j.cortex.2014.05.011
  • Peer Reviewed / Open Access
• [Journal Article] A functional polymorphism (C-824T) of the tyrosine hydroxylase gene affects intelligence quotient in schizophrenia (2014)
  • Author(s): Horiguchi M, Ohi K, Hashimoto R, Hao Q, Yasuda Y, Yamamori H, Fujimoto M, Umeda-Yano S, Takeda M, Ichinose H
  • Journal Title: Psychiatry and Clinical Neurosciences Volume: 68(6) Issue: 6 Pages: 456-62
  • DOI: 10.1111/pcn.12157
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Association between genetic polymorphism rs2952768, close to the METTL21A and CREB1 genes, and intellectual ability in healthy subjects. (2014)
  • Author(s): Nishizawa D, et al.
  • Journal Title: Journal of Addiction Research & Therapy Volume: in press
  • Peer Reviewed
• [Journal Article] Imaging genetics and psychiatric disorders. (2014)
  • Author(s): Hashimoto R, et al.
  • Journal Title: Current Molecular Medicine Volume: in press
  • Peer Reviewed
• [Journal Article] Expression analysis of the genes identified in GWAS of the postmortem brain tissues from patients with schizophrenia. (2014)
  • Author(s): Umeda-Yano S, et al.
  • Journal Title: Neuroscience Letters Volume: in press Pages: 12-6
  • DOI: 10.1016/j.neulet.2014.03.031
  • Peer Reviewed / Open Access
• [Journal Article] A functional polymorphism of the GTP cyclohydrolase I gene predicts attention performance (2014)
  • Author(s): Yasuda Y, Hashimoto R, Ohi K, Yamamori H, Fujimoto M, Umeda-Yano S, Fujino H, Horiguchi M, Takeda M, Ichinose H
  • Journal Title: Neurosci Lett Volume: 566 Pages: 46-49
  • DOI: 10.1016/j.neulet.2014.02.019
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Influence of the NRGN gene on intellectual ability in schizophrenia. (2013)
  • Author(s): Ohi K, et al.
  • Journal Title: Journal of Human Genetics, Volume: 58(10) Issue: 10 Pages: 700-5
  • DOI: 10.1038/jhg.2013.82
  • Peer Reviewed
• [Journal Article] How to diagnose the 22q11.2 deletion syndrome in patients with schizophrenia: a case report. (2013)
  • Author(s): Ohi K, et al.
  • Journal Title: Annals of General Psychiatry, Volume: 12(1) Issue: 1 Pages: 29-29
  • DOI: 10.1186/1744-859x-12-29
  • Peer Reviewed
• [Presentation] 統合失調症における生物学的マーカーとしての眼球運動スコアの信頼性 (2015)
  • Author(s): 藤本美智子、橋本亮太、三浦健一郎、山森英長、安田由華、大井一高、岩瀬真生、武田雅俊
  • Organizer: 第10回統合失調症学会
  • Place of Presentation: 東京
  • Year and Date: 2015-03-27 – 2015-03-28
• [Presentation] Glutamate Networks Implicate Cognitive Impairments in Schizophrenia; Genome-Wide Association Studies of 52 Cognitive Phenotypes. (2014)
  • Author(s): Ohi K, Hashimoto R, Ikeda M, Yamamori H, Yasuda Y, Fujimoto M, Umeda-Yano S, Fukunaga M, Fujino H, Watanabe Y, Iwase M, Kazui H, Iwata N, Weinberger DR, Takeda M.
  • Organizer: 2014 American College of Neuropharmachology(ACNP)
  • Place of Presentation: Phoenix, U.S.A
  • Year and Date: 2014-12-09
• [Presentation] 統合失調症患者由来サンプルを用いた統合失調症の病態解明研究 (2014)
  • Author(s): 橋本亮太、山森英長、梅田知美、藤本美智子、安田由華、伊藤彰、武田雅俊、
  • Organizer: 第11回NDDC-JSG会議
  • Place of Presentation: 大阪
  • Year and Date: 2014-10-07
• [Presentation] 統合失調症の生物学的マーカーとしての眼球運動スコアの開発 (2014)
  • Author(s): 藤本美智子、橋本亮太、三浦健一郎、山森英長、安田由華、大井一高、梅田知美、岩瀬真生、武田雅俊
  • Organizer: 第36回日本生物学的精神医学会・第57回日本神経化学会大会合同年会
  • Place of Presentation: 奈良
  • Year and Date: 2014-09-29 – 2014-10-01
• [Presentation] Eye movement abnormalities in patients with schizophrenia. (2013)
  • Author(s): Fujimoto M,
  • Organizer: 11th World Congress of Biological Psychiatry,
  • Place of Presentation: 京都
• [Book] 治療抵抗性統合失調症の治療戦略と病態研究-真の治療抵抗性統合失調症と見かけ上の治療抵抗性統合失調症、臨床精神薬理, (2014)
  • Author(s): 橋本亮太、安田由華、山森英長、藤本美智子、武田雅俊、
  • Publisher: 星和書店
• [Book] 急性期から回復期の治療、統合失調症ケーススタディー-症例が導く社会復帰・QOL向上への道- (2014)
  • Author(s): 橋本亮太、山森英長、安田由華、大井一高、藤本美智子、武田雅俊
  • Publisher: メディカルレビュー社
• [Book] 大阪大学では前薬をある程度継続しながら導入するのですか？クロザピン100のQ＆A- 治療抵抗性への挑戦- (2014)
  • Author(s): 橋本亮太、山森英長、安田由華、藤本美智子、武田雅俊、
  • Publisher: 星和書店
• [Book] 減量方法のテクニックを教えてください、クロザピン100のQ＆A- 治療抵抗性への挑戦- (2014)
  • Author(s): 橋本亮太、山森英長、安田由華、藤本美智子、武田雅俊、
  • Publisher: 星和書店
• [Book] クロザピン治療中のてんかん発作について教えてください、クロザピン100のQ＆A- 治療抵抗性への挑戦- (2014)
  • Author(s): 橋本亮太、山森英長、安田由華、藤本美智子、武田雅俊、
  • Publisher: 星和書店
• [Remarks] 分子精神医学研究グループ
  • URL: http://www.sp-web.sakura.ne.jp/lab/index.html
• [Remarks] 分子精神医学研究グループ
  • URL: http://www.sp-web.sakura.ne.jp/lab/index.html