Stratification of late onset psychosis using imaging biomarkers

• Project/Area Number: 19H03583
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 52030:Psychiatry-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Takahashi Hidehiko 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (60415429)
• Co-Investigator(Kenkyū-buntansha): 三村 將 慶應義塾大学, 医学部(信濃町), 教授 (00190728) ; 樋口 真人 国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 脳機能イメージング研究部, 部長(定常) (10373359)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000); Fiscal Year 2021: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2020: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2019: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
• Keywords: 遅発性精神病 / バイオマーカー / 脳画像 / 遅発性統合失調症 / イメージングバイオマーカー

Outline of Research at the Start

統合失調症は典型的には青年期に発症するが、中高年になって初めて幻覚妄想を呈する遅発性精神病と呼ばれる一群がある。これらは生物学的に異なる疾患であるか、異なる場合、遅発性精神病は認知症の前駆期であるかに関して、鑑別が困難である。代表者らが開発した安静時fMRIによる典型例統合失調症のバイオマーカーを遅発性精神病に適用し、典型的な統合失調症らしさが高い群と低い群を抽出する。次に両群にタウ・アミロイドPETを実施する。MRIとPETによる画像バイオマーカーによって遅発性精神病の鑑別方法を確立する。

Outline of Final Research Achievements

At the time of application, a paper on biomarkers of schizophrenia by functional brain connectivity obtained by resting-state fMRI, which was ready for submission, was accepted and published (Yoshihara et al Schizophr Bull 2020). Based on the spatial distribution of tau lesions, the following patterns were considered: (1) a pattern typical of Alzheimer's disease, (2) a pattern of frontotemporal lobe degeneration such as basal ganglia degeneration and Pick's disease, and (3) a pattern that does not fit either (1) or (2) but is observed for the first time in this study, with accumulation in the cortical regions. Among these, late-onset psychosis, which was judged unlikely to be schizophrenia, was expected to present the novel pattern (3) more frequently.

Academic Significance and Societal Importance of the Research Achievements

遅発性精神病が認知症の前駆期であるか否かを判別することは、長い精神医学の歴史の中でも学問上、常に重要なテーマであったとともに、臨床の上でも統鑑別可能となれば、不適切な向精神薬の投与を軽減し、早期から認知症の予防の策を講じることも可能となり、医療・福祉への波及効果も大きい。

Research Products

• [Int'l Joint Research] Oxford 大学(英国)
• [Int'l Joint Research] johns hopkins university(米国)
• [Int'l Joint Research] University Medical Center Utrecht(オランダ)
• [Journal Article] Decision tree classification of cognitive functions with D2 receptor occupancy and illness severity in late-life schizophrenia (2022)
  • Author(s): Kusudo Keisuke、Ochi Ryo、Nakajima Shinichiro、Suzuki Takefumi、Mamo David、Caravaggio Fernando、Mar Wanna、Gerretsen Philip、Mimura Masaru、Pollock Bruce G.、Mulsant Benoit H.、Graff-Guerrero Ariel、Rajji Tarek K.、Uchida Hiroyuki
  • Journal Title: Schizophrenia Research Volume: 241 Pages: 113-115
  • DOI: 10.1016/j.schres.2022.01.044
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A multi-site, multi-disorder resting-state magnetic resonance image database. (2021)
  • Author(s): Tanaka SC, Yamashita A, Yahata N, Itahashi T
  • Journal Title: Sci Data Volume: 8 Issue: 1 Pages: 227-227
  • DOI: 10.1038/s41597-021-01004-8
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Natural and Artificial Intelligence: A brief introduction to the interplay between AI and neuroscience research (2021)
  • Author(s): Macpherson Tom、Churchland Anne、Sejnowski Terry、DiCarlo James、Kamitani Yukiyasu、Takahashi Hidehiko、Hikida Takatoshi
  • Journal Title: Neural Networks Volume: 144 Pages: 603-613
  • DOI: 10.1016/j.neunet.2021.09.018
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Three-Dimensional Convolutional Autoencoder Extracts Features of Structural Brain Images With a “Diagnostic Label-Free” Approach: Application to Schizophrenia Datasets (2021)
  • Author(s): Yamaguchi Hiroyuki、Hashimoto Yuki、Sugihara Genichi、Miyata Jun、Murai Toshiya、Takahashi Hidehiko、Honda Manabu、Hishimoto Akitoyo、Yamashita Yuichi
  • Journal Title: Frontiers in Neuroscience Volume: 15 Pages: 652987-652987
  • DOI: 10.3389/fnins.2021.652987
  • Peer Reviewed / Open Access
• [Journal Article] Common Brain Networks Between Major Depressive-Disorder Diagnosis and Symptoms of Depression That Are Validated for Independent Cohorts (2021)
  • Author(s): Yamashita Ayumu、et al、Harada Kenichiro、Matsuo Koji、Tanaka Saori C.、Kawato Mitsuo、Kasai Kiyoto、Kato Nobumasa、Takahashi Hidehiko、Okamoto Yasumasa、Yamashita Okito、Imamizu Hiroshi
  • Journal Title: Frontiers in Psychiatry Volume: 12
  • DOI: 10.3389/fpsyt.2021.667881
  • Peer Reviewed / Open Access
• [Journal Article] Glutamatergic and GABAergic metabolite levels in schizophrenia-spectrum disorders: a meta-analysis of 1H-magnetic resonance spectroscopy studies (2021)
  • Author(s): Nakahara T, Tsugawa S, Noda Y, Ueno F, Honda S, Kinjo M, Segawa H, Hondo N, Mori Y, Watanabe H, Nakahara K, Yoshida K, Wada M, Tarumi R, Iwata Y, Plitman E, Moriguchi S, de la Fuente-Sandoval C, Nakajima S.
  • Journal Title: Molecular Psychiatry Volume: 27 Issue: 1 Pages: 744-757
  • DOI: 10.1038/s41380-021-01297-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Neural Correlates of Mild Behavioral Impairment: A Functional Brain Connectivity Study Using Resting-State Functional Magnetic Resonance Imaging (2021)
  • Author(s): Matsuoka Teruyuki、Ueno Daisuke、Ismail Zahinoor、Rubinstein Ellen、Uchida Hiroyuki、Mimura Masaru、Narumoto Jin
  • Journal Title: Journal of Alzheimer's Disease Volume: 83 Issue: 3 Pages: 1221-1231
  • DOI: 10.3233/jad-210628
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Evaluation of [18F]PI-2620, a second-generation selective tau tracer, for assessing four-repeat tauopathies (2021)
  • Author(s): Tezuka Toshiki、et al 、Miura Eisuke、Yamamoto Yasuharu、Sano Yasunori、Funaki Kei、Yamagata Bun、Ueda Ryo、Yoshizaki Takahito、Mashima Kyoko、Shibata Mamoru、Oyama Munenori、Okada Kensuke、Kubota Masahito、Okita Hajime、Takao Masaki、Jinzaki Masahiro、Nakahara Jin、Mimura Masaru、Ito Daisuke
  • Journal Title: Brain Communications Volume: 3 Issue: 4
  • DOI: 10.1093/braincomms/fcab190
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Dimensional distribution of cortical abnormality across antipsychotics treatment-resistant and responsive schizophrenia (2021)
  • Author(s): Itahashi Takashi、Noda Yoshihiro、Iwata Yusuke、Tarumi Ryosuke、Tsugawa Sakiko、Plitman Eric、Honda Shiori、Caravaggio Fernando、Kim Julia、Matsushita Karin、Gerretsen Philip、Uchida Hiroyuki、Remington Gary、Mimura Masaru、Aoki Yuta Y.、Graff-Guerrero Ariel、Nakajima Shinichiro
  • Journal Title: NeuroImage: Clinical Volume: 32 Pages: 102852-102852
  • DOI: 10.1016/j.nicl.2021.102852
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Relationship between regional gray matter volumes and dopamine D2 receptor and transporter in living human brains (2021)
  • Author(s): Kurose Shin、Kubota Manabu、Takahata Keisuke、Yamamoto Yasuharu、Fujiwara Hironobu、Kimura Yasuyuki、Ito Hiroshi、Takeuchi Hiroyoshi、Mimura Masaru、Suhara Tetsuya、Higuchi Makoto
  • Journal Title: Human Brain Mapping Volume: - Issue: 12 Pages: 4048-4058
  • DOI: 10.1002/hbm.25538
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cryo-EM structures of tau filaments from Alzheimer’s disease with PET ligand APN-1607 (2021)
  • Author(s): Shi Yang、Murzin Alexey G.、Falcon Benjamin、Epstein Alexander、Machin Jonathan、Tempest Paul、Newell Kathy L.、Vidal Ruben、Garringer Holly J.、Sahara Naruhiko、Higuchi Makoto、Ghetti Bernardino、Jang Ming-Kuei、Scheres Sjors H. W.、Goedert Michel
  • Journal Title: Acta Neuropathologica Volume: 141 Issue: 5 Pages: 697-708
  • DOI: 10.1007/s00401-021-02294-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] High-Contrast In Vivo Imaging of Tau Pathologies in Alzheimer’s and Non-Alzheimer’s Disease Tauopathies (2021)
  • Author(s): Tagai K, Ono M, Kubota M, Kitamura S, Takahata K, Seki C, Takado Y, Shinotoh H, Sano Y, Yamamoto Y, Matsuoka K, Takuwa H, Shimojo M, (24人省略), Shimada H.
  • Journal Title: Neuron Volume: 109 Issue: 1 Pages: 42-58
  • DOI: 10.1016/j.neuron.2020.09.042
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Comparison of MRI-based and PET-based image pre-processing for quantification of 11C-PBB3 uptake in human brain (2021)
  • Author(s): Yousefzadeh-Nowshahr Elham、Winter Gordon、Bohn Peter、Kneer Katharina、von Arnim Christine A.F.、Otto Markus、Solbach Christoph、Anderl-Straub Sarah、Polivka D?rte、Fissler Patrick、Prasad Vikas、Kletting Peter、Riepe Matthias W.、Higuchi Makoto、Ludolph Albert、Beer Ambros J.、Glatting Gerhard
  • Journal Title: Zeitschrift f?r Medizinische Physik Volume: 31 Issue: 1 Pages: 37-47
  • DOI: 10.1016/j.zemedi.2020.12.002
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Overlapping but Asymmetrical Relationships Between Schizophrenia and Autism Revealed by Brain Connectivity. (2020)
  • Author(s): Yujiro Yoshihara, Giuseppe Lisi, Noriaki Yahata, Junya Fujino, Yukiko Matsumoto, Jun Miyata, Gen-Ichi Sugihara, Shin-Ichi Urayama, Manabu Kubota et al.
  • Journal Title: Schizophrenia Bulletin Volume: 4 Issue: 5 Pages: 1210-1218
  • DOI: 10.1093/schbul/sbaa021
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Cognition and interpersonal coordination of patients with schizophrenia who have sports habits (2020)
  • Author(s): Fujii Keisuke、Yoshihara Yujiro、Matsumoto Yukiko、Tose Keima、Takeuchi Hideaki、Isobe Masanori、Mizuta Hiroto、Maniwa Daisuke、Okamura Takehiko、Murai Toshiya、Kawahara Yoshinobu、Takahashi Hidehiko
  • Journal Title: PLOS ONE Volume: 15 Issue: 11 Pages: e0241863-e0241863
  • DOI: 10.1371/journal.pone.0241863
  • Peer Reviewed / Open Access
• [Journal Article] Radiosynthesis and quality control testing of the tau imaging positron emission tomography tracer [ 18 F]PM‐PBB3 for clinical applications (2020)
  • Author(s): Kawamura Kazunori、Hashimoto Hiroki、Furutsuka Kenji、Ohkubo Takayuki、Fujishiro Tomoya、Togashi Takahiro、Arashi Daisuke、Sakai Toshiyuki、Muto Masatoshi、Ogawa Masanao、Kurihara Yusuke、Nengaki Nobuki、Takei Makoto、Nemoto Kazuyoshi、Higuchi Makoto、Zhang Ming‐Rong
  • Journal Title: Journal of Labelled Compounds and Radiopharmaceuticals Volume: 64 Issue: 3 Pages: 109-119
  • DOI: 10.1002/jlcr.3890
  • Peer Reviewed
• [Journal Article] Excess tau PET ligand retention in elderly patients with major depressive disorder (2020)
  • Author(s): Moriguchi Sho、Takahata Keisuke、Shimada Hitoshi、Kubota Manabu、Kitamura Soichiro、Kimura Yasuyuki、Tagai Kenji、Tarumi Ryosuke、Tabuchi Hajime、Meyer Jeffrey H.、Mimura Masaru、Kawamura Kazunori、Zhang Ming-Rong、Murayama Shigeo、Suhara Tetsuya、Higuchi Makoto
  • Journal Title: Molecular Psychiatry Volume: Online ahead of print Issue: 10 Pages: 5856-5863
  • DOI: 10.1038/s41380-020-0766-9
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] PET-detectable tau pathology correlates with long-term neuropsychiatric outcomes in patients with traumatic brain injury (2019)
  • Author(s): Takahata K、Kimura Yi、Sahara N、Koga S、Shimada H、Ichise M、Saito F、Moriguchi S、Kitamura S、Kubota M、Umeda S、Niwa F、Mizushima J、Morimoto Y、Funayama M、Tabuchi H、Bieniek K. F、Kawamura K、Zhang Ming-Rong、Dickson D. W、Mimura M、Kato M、Suhara T、Higuchi M
  • Journal Title: Brain Volume: 142 Issue: 10 Pages: 3265-3279
  • DOI: 10.1093/brain/awz238
  • Peer Reviewed / Int'l Joint Research
• [Presentation] 脳画像から統合失調症の早期死亡を考える (2021)
  • Author(s): 髙橋 英彦
  • Organizer: 第43回 日本生物学的精神医学会
  • Invited
• [Presentation] AI技術を用いたニューロフィードバックの精神疾患への応用 (2021)
  • Author(s): 髙橋 英彦
  • Organizer: 第６回?CEPD研究会
  • Invited
• [Presentation] Multimodal PET (2021)
  • Author(s): Makoto Higuchi
  • Organizer: International Conference of Korean Movement Disorder Society
  • Int'l Joint Research / Invited
• [Presentation] 認知症イメージングの国際展開 (2021)
  • Author(s): 樋口 真人
  • Organizer: 第42回日本臨床薬理学会学術総会
  • Invited
• [Presentation] 画像バイオマーカーを駆使した 次世代認知症診療システムの構築 (2021)
  • Author(s): 樋口 真人
  • Organizer: 日本脳神経外科学会 第80回学術総会
  • Invited
• [Presentation] 精神疾患と神経疾患をつなぐ生体イメージング研究開発 (2021)
  • Author(s): 樋口 真人
  • Organizer: 第43回日本生物学的精神医学会・第51回日本神経精神薬理学会合同年会
  • Invited
• [Presentation] 精神・神経疾患のイメージングバイオマーカー (2021)
  • Author(s): 樋口 真人
  • Organizer: 第121回日本医学物理学会学術集会
  • Invited
• [Presentation] Molecular imaging in neurodegeneration: look to the future and implement in the reality (2021)
  • Author(s): Makoto Higuchi
  • Organizer: 2021 Asian and Oceanian Congress of Neurology
  • Int'l Joint Research / Invited
• [Presentation] Multimodal Imaging of Tau and α-Synuclein Pathologies (2021)
  • Author(s): Makoto Higuchi
  • Organizer: The 15th International Conference on Alzheimer’s and Parkinson’s Diseases (ADPD 2021)
  • Int'l Joint Research / Invited
• [Presentation] : MRI and PET imaging features of retired athletes with repetitive mild traumatic brain injury (2021)
  • Author(s): Miyata M, Takahata K, Mimura M, Higuchi M
  • Organizer: RSNA2021, 2021.11.28-12.2, Chicago, USA (WEB開催)
  • Int'l Joint Research
• [Presentation] Brain pathology of 18 supercentenarians aged 110 and over (2021)
  • Author(s): Takao M, Mihara B, Arai Y, Murakami T, Nose S, Hamaya K, Nishida K, Futamura N, Nakayama Y, Mizutani T, Sano T, Okano H, Mimura M, Kanai Y, Hirose N
  • Organizer: The 98th Annual Meeting of the American Association of Neuropathologists, 2021.6.10-12, Web.
  • Int'l Joint Research
• [Presentation] : 高齢発症の双極性障害患者における脳内アミロイド・タウ蓄積、神経心理症状の評価: 11C-PiB, 18F-PM-PBB3を用いた縦断PET研究 (2021)
  • Author(s): 佐野康徳, 高畑圭輔, 森口 翔, 山本保天, 黒瀬 心, 小久保奈緒美, 小西海香, 瓦 健二, 平田浩聖, 松岡 究, 遠藤浩信, 高堂祐平, 斎藤文恵, 樋口真人, 三村 將
  • Organizer: 第45回日本神経心理学会学術集会, 日本教育会館＋WEB開催, 2021.9.30
• [Presentation] 語義失語様の症状を呈す進行性失語で非AD・tauopathyが疑われる一例 (2021)
  • Author(s): 小西海香, 斎藤文恵, 手塚俊樹, 田渕 肇, 三村 將
  • Organizer: 第45回日本神経心理学会学術集会, 日本教育会館＋WEB開催, 2021.10.1
• [Presentation] 聴覚失認とプロソディ障害で発症し、[18F]PM-PBB3 PETで診断に至ったtauopathyの1例 (2021)
  • Author(s): 馬島 恭子, 小西 海香, 手塚 俊樹, 高畑 圭輔, 岡本 康秀, 関 守信, 田淵 肇, 伊東 大介, 三村 將
  • Organizer: 第40回日本認知症学会学術集会, 2021.11.26-11.28, 国際フォーラム(ハイブリッド開催)
• [Presentation] [18F]PM-PBB3と血漿中のp-tau181およびNfLによるアルツハイマー病の診断 (2021)
  • Author(s): 手塚 俊樹, 高畑 圭輔, 関 守信, 文 鐘玉, 佐藤 義明, 上田 亮, 窪田 真人, 森口 翔, 中島 振一郎, 鈴木 菜摘, 森本 綾香, 百田 友紀, 岩渕 雄, 馬島 恭子, 田渕 肇, 陣崎 雅弘, 三村 將, 中原 仁, 伊東 大介
  • Organizer: 第40回日本認知症学会学術集会, 2021.11.26-11.28, 国際フォーラム(ハイブリッド開催)
• [Presentation] Interface between AI and schizophrenia research (2020)
  • Author(s): Hidehiko Takahashi
  • Organizer: International Symposium on Artificial Intelligence and Brain Science
  • Int'l Joint Research / Invited
• [Presentation] Interface between AI and schizophrenia research (2020)
  • Author(s): Hidehiko Takahashi
  • Organizer: 日本神経科学会
  • Invited
• [Presentation] Altered decision-making as an endophenotype to bridge the gap between phenomenology and neurobiology (2019)
  • Author(s): Hidehiko Takahashi
  • Organizer: International Symposium of Personalized value: Interdisciplinary approach
  • Int'l Joint Research / Invited
• [Presentation] 脳イメージングと人工知能を統合失調症研究に活かす (2019)
  • Author(s): 高橋 英彦
  • Organizer: ヒト脳イメージング研究会
  • Invited
• [Presentation] 3脳画像で見た統合失調症の脳構造異常の経時的変化 (2019)
  • Author(s): 高橋 英彦
  • Organizer: アジア神経精神薬理学会
  • Invited