Mechanism of eye movement abnormality as an endophenotype in patients with schizophrenia

• Project/Area Number: 17K10300
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Osaka University
• Principal Investigator: Fujimoto Michiko 大阪大学, 医学系研究科, 医学部講師 (50647625)
• Co-Investigator(Kenkyū-buntansha): 安田 由華 大阪大学, 医学部附属病院, 特任助教(常勤) (20448062) ; 山森 英長 大阪大学, 医学系研究科, 講師 (90570250) ; 工藤 紀子 大阪大学, 情報科学研究科, 特任研究員 (30751151) ; 畦地 裕統 大阪大学, 連合小児発達学研究科, 特任研究員 (90615296)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 統合失調症 / 眼球運動異常 / 中間表現型 / 生物学的精神医学 / 眼球運動

Outline of Final Research Achievements

We analyzed the factor which distinguished patients with schizophrenia from healthy controls based on the characteristics of eye movement and other endophenotypes. The result showed Social Functioning Scale (SFS) was the most promising factor that distinguished patients with schizophrenia from healthy controls. Furthermore, clozapine improved the eye movement score and cognitive impairment on patients with treatment-resistant schizophrenia, suggesting that the eye movement score might be a state-dependent marker of schizophrenia. We successfully replicated the high correct rate in the discriminant analysis between patients with schizophrenia and healthy controls after change the eye movement measurement system to the new one.

Academic Significance and Societal Importance of the Research Achievements

統合失調症の補助診断法として注目されている検査の一つが眼球運動検査である。統合失調症患者においては追跡眼球運動が円滑に行えず、注視課題が遂行困難であり、また探索眼球運動では眼球の動きが少ないことが特徴とされている。統合失調症患者と健常者について判別度の高い眼球運動指標は未だ確立されておらず、眼球運動異常のメカニズムも明らかになっていない。そこで、眼球運動など種々の中間表現型の関連を調べることにより中間表現型の疾患バイオマーカーとしての有用性を明らかにし、また生物学的な病態の理解が進むことで、本研究成果が疾患の予防、早期診断、早期介入および治療に役立つことが期待される。

Research Products

• [Journal Article] Differences in fractional anisotropy between the patients with schizophrenia and healthy comparison subjects. (2020)
  • Author(s): Koshiyama D, Fukunaga M, Okada N, Morita K, Nemoto K, Usui K, Yamamori H, Yasuda Y, Fujimoto M, et al.
  • Journal Title: Mol Psychiatry Volume: 25(4) Issue: 4 Pages: 697-698
  • DOI: 10.1038/s41380-020-0700-1
  • NAID: 120006950307
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Ethnicity-Dependent Effects of Schizophrenia Risk Variants of the OLIG2 Gene on OLIG2 Transcription and White Matter Integrity (2020)
  • Author(s): Komatsu H, Takeuchi H, Kikuchi Y, Ono C, Yu Z, Iizuka K, Takano Y, Kakuto Y, Funakoshi S, Ono T, Ito J, Kunii Y, Hino M, Nagaoka A, Iwasaki Y, Yamamori H, Yasuda Y, Fujimoto M, Azechi H, Kudo N, Hashimoto R, Yabe H, Yoshida M, Saito Y, Kakita A, Fuse N, Kawashima R, Taki Y, Tomita H
  • Journal Title: Schizophrenia Bulletin Volume: - Issue: 6 Pages: 1619-1628
  • DOI: 10.1093/schbul/sbaa049
  • Peer Reviewed / Open Access
• [Journal Article] Pathogenic POGZ mutation causes impaired cortical development and reversible autism-like phenotypes. (2020)
  • Author(s): Matsumura K, (33名中略）, Hashimoto R, (37名中35番目）,Hashimoto H, Nakazawa T.
  • Journal Title: Nat. Commun Volume: 11(1) Issue: 1 Pages: 859-859
  • DOI: 10.1038/s41467-020-14697-z
  • Peer Reviewed / Open Access
• [Journal Article] Plasma levels of matrix metalloproteinase‐9 (MMP‐9) are associated with cognitive performance in patients with schizophrenia (2020)
  • Author(s): Kudo Noriko、Yamamori Hidenaga、Ishima Tamaki、Nemoto Kiyotaka、Yasuda Yuka、Fujimoto Michiko、Azechi Hirotsugu、Niitsu Tomihisa、Numata Shusuke、Ikeda Manabu、Iyo Masaomi、Ohmori Tetsuro、Fukunaga Masaki、Watanabe Yoshiyuki、Hashimoto Kenji、Hashimoto Ryota
  • Journal Title: Neuropsychopharmacology Reports Volume: - Issue: 2 Pages: 150-156
  • DOI: 10.1002/npr2.12098
  • NAID: 120007027668
  • Peer Reviewed / Open Access
• [Journal Article] Brain morphological and functional features in cognitive subgroups of Schizophrenia. (2020)
  • Author(s): Yasuda Y, Okada N, Nemoto K, Fukunaga M, Yamamori H, Ohi K, Koshiyama D, Kudo N, Shiino T, Morita S, Morita K, Azechi H, Fujimoto M, Miura K, Watanabe Y, Kasai K, Hashimoto R.
  • Journal Title: Psychiatry Clin Neurosci Volume: 74(3) Issue: 3 Pages: 191-203
  • DOI: 10.1111/pcn.12963
  • NAID: 120007132757
  • Peer Reviewed / Open Access
• [Journal Article] Comparison of eye movements in schizophrenia and autism spectrum disorder. (2020)
  • Author(s): Shiino T, Miura K, Fujimoto M, Kudo N, Yamamori H, Yasuda Y,Ikeda M, Hashimoto R.
  • Journal Title: Neuropsychopharmacol Rep Volume: 40(1) Issue: 1 Pages: 92-95
  • DOI: 10.1002/npr2.12085
  • Peer Reviewed / Open Access
• [Journal Article] White matter microstructural alterations across four major psychiatric disorders: mega-analysis study in 2937 individuals (2019)
  • Author(s): Koshiyama Daisuke、(他38名18番目）Yamamoto Meeri
  • Journal Title: Molecular Psychiatry Volume: 25 Issue: 4 Pages: 883-895
  • DOI: 10.1038/s41380-019-0553-7
  • NAID: 120006980539
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A 1.5-year longitudinal study of social activity in patients with schizophrenia. (2019)
  • Author(s): Ohi K, Sumiyoshi C, Fujino H, Yasuda Y, Yamamori H, Fujimoto M, Sumiyoshi T, Hashimoto R.
  • Journal Title: Front Psychiatry, section Schizophrenia Volume: 10 Pages: 567-567
  • DOI: 10.3389/fpsyt.2019.00567
  • Peer Reviewed / Open Access
• [Journal Article] Eye movement characteristics of schizophrenia and their association with cortical thickness. (2019)
  • Author(s): Morita K, Hashimoto R, et al.
  • Journal Title: Psychiat Clin Neurosci Volume: 73 Issue: 8 Pages: 508-509
  • DOI: 10.1111/pcn.12865
  • Peer Reviewed / Open Access
• [Journal Article] Eye movement abnormalities and their association with cognitive impairments in schizophrenia. (2019)
  • Author(s): Morita K, Miura K, Fujimoto M, Yamamori H, Yasuda Y, Kudo N, Azechi H, Okada N, Koshiyama D, Ikeda M, Kasai K, Hashimoto R.
  • Journal Title: Schizophr Res Volume: 209 Pages: 255-262
  • DOI: 10.1016/j.schres.2018.12.051
  • Peer Reviewed / Open Access
• [Journal Article] Frequency of mental disorders among chronic pain patients with or without fibromyalgia in Japan. (2019)
  • Author(s): Miki K, Nakae A, Shi K, Yasuda Y, Yamamori H, Fujimoto M, Ikeda M, Shibata M, Yukioka M, Hashimoto R.
  • Journal Title: Neuropsychopharmacol Rep Volume: 38(4) Issue: 4 Pages: 167-174
  • DOI: 10.1002/npr2.12025
  • Peer Reviewed / Open Access
• [Journal Article] Abnormalities of eye movement are associated with work hours in schizophrenia. (2018)
  • Author(s): Morita K, Miura K, Fujimoto M, Shishido E, Shiino T, Takahashi J, Yamamori H, Yasuda Y, Kudo N, Hirano Y, Koshiyama D, Okada N, Ikeda M, Onitsuka T, Ozaki N, Kasai K, Hashimoto R.
  • Journal Title: Schizophr Res Volume: 202 Pages: 420-422
  • DOI: 10.1016/j.schres.2018.06.064
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Role of frontal white matter and corpus callosum on social function in schizophrenia. (2018)
  • Author(s): Koshiyama D, Fukunaga M, Okada N, Morita K, Nemoto K, Yamashita F, Yamamori H, Yasuda Y, Fujimoto M, Kelly S, Jahanshad N, Kudo N, Azechi H, Watanabe Y, Donohoe G, Thompson PM, Kasai K, Hashimoto R.
  • Journal Title: Schizophr Res Volume: 202 Pages: 180-187
  • DOI: 10.1016/j.schres.2018.07.009
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Genetic Overlap between General Cognitive Function and Schizophrenia: A Review of Cognitive GWASs. (2018)
  • Author(s): Ohi K, Sumiyoshi C, Fujino H, Yasuda Y, Yamamori H, Fujimoto M, Shiino T, Sumiyoshi T, Hashimoto R.
  • Journal Title: Int J Mol Sci Volume: 19(12) Issue: 12 Pages: 3822-3822
  • DOI: 10.3390/ijms19123822
  • Peer Reviewed / Open Access
• [Journal Article] Predicting work outcome in patients with schizophrenia: Influence of IQ decline. (2018)
  • Author(s): Sumiyoshi C, Fujino H, Yamamori H, Kudo N, Azechi H, Fujimoto M, Yasuda Y, Ohi K, Sumiyoshi T, Hashimoto R.
  • Journal Title: Schizophr Res Volume: 201 Pages: 172-179
  • DOI: 10.1016/j.schres.2018.05.042
  • Peer Reviewed / Open Access
• [Journal Article] Genome-wide Association Analysis of Eye Movement Dysfunction in Schizophrenia. (2018)
  • Author(s): Kikuchi M, Miura K, Morita K, Yamamori H, Fujimoto M, Ikeda M, Yasuda Y, Nakaya A, uHashimoto R.
  • Journal Title: Sci Rep Volume: 8(1) Issue: 1 Pages: 12347-12347
  • DOI: 10.1038/s41598-018-30646-9
  • NAID: 120006549303
  • Peer Reviewed / Open Access
• [Journal Article] Plasma Levels of Soluble Tumor Necrosis Factor Receptor 2 (sTNFR2) Are Associated with Hippocampal Volume and Cognitive Performance in Patients with Schizophrenia. (2018)
  • Author(s): Kudo N, Yamamori H, Ishima T, Nemoto K, Yasuda Y, Fujimoto M, Azechi H, Niitsu T, Numata S, Ikeda M, Iyo M, Ohmori T, Fukunaga M, Watanabe Y, Hashimoto K, Hashimoto R.
  • Journal Title: Int J Neuropsychopharmacol Volume: 21(7) Issue: 7 Pages: 631-639
  • DOI: 10.1093/ijnp/pyy013
  • NAID: 120006772559
  • Peer Reviewed / Open Access
• [Journal Article] Semantic Memory Organization in Japanese Patients With Schizophrenia Examined With Category Fluency (2018)
  • Author(s): Sumiyoshi Chika、Fujino Haruo、Sumiyoshi Tomiki、Yasuda Yuka、Yamamori Hidenaga、Fujimoto Michiko、Hashimoto Ryota
  • Journal Title: Frontiers in Psychiatry Volume: 9 Pages: 1-10
  • DOI: 10.3389/fpsyt.2018.00087
  • Peer Reviewed / Open Access
• [Journal Article] Role of subcortical structures on cognitive and social function in schizophrenia (2018)
  • Author(s): Koshiyama Daisuke、Fukunaga Masaki、Okada Naohiro、Yamashita Fumio、Yamamori Hidenaga、Yasuda Yuka、Fujimoto Michiko、Ohi Kazutaka、Fujino Haruo、Watanabe Yoshiyuki、Kasai Kiyoto、Hashimoto Ryota
  • Journal Title: Sci Rep Volume: 8 Issue: 1 Pages: 1183-1183
  • DOI: 10.1038/s41598-017-18950-2
  • Peer Reviewed / Open Access
• [Journal Article] Subcortical association with memory performance in schizophrenia: a structural magnetic resonance imaging study (2018)
  • Author(s): Koshiyama Daisuke、Fukunaga Masaki、Okada Naohiro、Yamashita Fumio、Yamamori Hidenaga、Yasuda Yuka、Fujimoto Michiko、Ohi Kazutaka、Fujino Haruo、Watanabe Yoshiyuki、Kasai Kiyoto、Hashimoto Ryota
  • Journal Title: Transl Psychiatry Volume: 8 Issue: 1 Pages: 20-20
  • DOI: 10.1038/s41398-017-0069-3
  • Peer Reviewed / Open Access
• [Journal Article] The effect of duration of illness and antipsychotics on subcortical volumes in schizophrenia: Analysis of 778 subjects (2018)
  • Author(s): Hashimoto Naoki、Ito Yoichi M.、Okada Naohiro、Yamamori Hidenaga、Yasuda Yuka、Fujimoto Michiko、et al.
  • Journal Title: Neuroimage Clin Volume: 17 Pages: 563-569
  • DOI: 10.1016/j.nicl.2017.11.004
  • NAID: 120006463564
  • Peer Reviewed / Open Access
• [Journal Article] A Brief Assessment of Intelligence Decline in Schizophrenia As Represented by the Difference between Current and Premorbid Intellectual Quotient (2017)
  • Author(s): Ohi Kazutaka、Sumiyoshi Chika、Fujino Haruo、Yasuda Yuka、Yamamori Hidenaga、Fujimoto Michiko、Sumiyoshi Tomiki、Hashimoto Ryota
  • Journal Title: Frontiers in Psychiatry Volume: 8 Pages: 1-10
  • DOI: 10.3389/fpsyt.2017.00293
  • Peer Reviewed / Open Access
• [Journal Article] Estimated cognitive decline in patients with schizophrenia: A multicenter study. (2017)
  • Author(s): Fujino H, Sumiyoshi C, Yasuda Y, Yamamori H, Fujimoto M, Fukunaga M, Miura K, Takebayashi Y, Okada N, Isomura S, Kawano N, Toyomaki A, Kuga H, Isobe M, Oya K, Okahisa Y, Takaki M, Hashimoto N, Kato M, Onitsuka T, Ueno T, Ohnuma T, Kasai K, Ozaki N, Sumiyoshi T, Imura O, Hashimoto R
  • Journal Title: sychiatry Clin Neurosci. Volume: 印刷中 Issue: 5 Pages: 294-300
  • DOI: 10.1111/pcn.12474
  • Peer Reviewed / Open Access
• [Presentation] Clozapine投与中の治療抵抗性統合失調症患者における簡易認知機能検査の実践 (2019)
  • Author(s): 藤本美智子、山森英長、安田由華、工藤紀子、畦地裕統、住吉チカ、藤野陽生、住吉太幹、池田学、橋本亮太
  • Organizer: 第19回精神疾患と認知機能研究会
• [Presentation] Clozapine-induced seizure complicated with vertebral fracture, leg paralysis and pulmonary embolism in a patient with treatment-resistant schizophrenia (2019)
  • Author(s): Michiko Fujimoto, Daiki Taomoto, Shigeki Katakami, Tsubasa Omi, Ryota Hashimoto, Hidenaga Yamamori, Yuka Yasuda, Takahiro Makino, Hideki Yoshikawa, Masao Iwase, Manabu Ikeda
  • Organizer: Asian College of Neuropsychopharmacology
  • Int'l Joint Research
• [Presentation] 統合失調症における眼球運動特性の診断補助的指標としての再現性 (2019)
  • Author(s): 藤本美智子、三浦健一郎、森田健太郎、工藤紀子、畦地裕統、山森英長、安田由華、池田学、橋本亮太
  • Organizer: 第39回日本精神科診断学会
• [Presentation] Clozapineにより好酸球増加症が生じたが継続投与が可能であった治療抵抗性統合失調症の一例 (2019)
  • Author(s): 藤本美智子、山森英長、安田由華、加藤恒、金倉譲、岩瀬真生、池田学、橋本亮太
  • Organizer: 第115回日本精神神経学会
• [Presentation] 統合失調症におけるバイオマーカーとしての眼球運動スコアの臨床的意義 (2019)
  • Author(s): 藤本美智子、三浦健一郎、森田健太郎、工藤紀子、畦地裕統、山森英長、安田由華、池田学、橋本亮太
  • Organizer: 第41回日本生物学的精神医学会第8回若手研究者育成プログラム
• [Presentation] 統合失調症のクロザピン治療による中間表現型の変化 (2018)
  • Author(s): 藤本美智子、三浦健一郎、森田健太郎、工藤紀子、畦地裕統、山森英長、安田由華、池田学、橋本亮太
  • Organizer: 第28回日本臨床精神神経薬理学会第48回日本神経精神薬理学会合同年会
• [Presentation] 統合失調症の眼球運動スコアに影響する因子 (2017)
  • Author(s): 藤本美智子、三浦健一郎、森田健太郎、山森英長、安田由華、橋本亮太
  • Organizer: 第39回日本生物学的精神医学会第49会日本神経精神薬理学会合同年会
• [Presentation] 統合失調症におけるバイオマーカーとしての眼球運動スコアの臨床的意義 (2017)
  • Author(s): 2.藤本美智子、三浦健一郎、森田健太郎、山森英長、安田由華、工藤紀子、奥田詩織、岩瀬真生、笠井清登
  • Organizer: 第39回日本生物学的精神医学会
• [Presentation] 統合失調症患者の眼球運動障害における治療抵抗性の影響 (2017)
  • Author(s): 3.藤本美智子、三浦健一郎、森田健太郎、山森英長、安田由華、工藤紀子、奥田詩織、岩瀬真生、池田学、笠井清登、橋本亮太
  • Organizer: 第113回日本精神神経学会学術総会
• [Remarks] 大阪大学大学院医学系研究科精神医学教室 生物学的精神医学研究グループ
  • URL: http://www2.med.osaka-u.ac.jp/psy/laboratories/lab05/
• [Remarks] 大阪大学大学院医学系研究科精神医学教室 分子精神医学研究グループ
  • URL: http://www.sp-web.sakura.ne.jp/lab/index.html