Classification of schizophrenia-related disorders by multimodal neuroimaging assessments of PDE10A
Project/Area Number |
19K17101
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 52030:Psychiatry-related
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Research Institution | Kyoto University (2020-2022) National Institutes for Quantum and Radiological Science and Technology (2019) |
Principal Investigator |
Kubota Manabu 京都大学, 医学研究科, 助教 (30760368)
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Project Period (FY) |
2019-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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Keywords | 統合失調症 / ホスホジエステラーゼ / PDE10A / PET / MRS / striatum / cognition / [18F]MNI659 / phosphodiesterase / 陽電子放出断層撮像 |
Outline of Research at the Start |
脳内ドーパミン神経伝達の異常は、統合失調症の病態生理の中核をなす。ホスホジエステラーゼ10A (PDE10A)はドーパミンの働きを制御する細胞内酵素であり、過去の研究から統合失調症の病態に深く関わると考えられている。本研究では、統合失調症患者を対象としてPDE10Aを標的とした陽電子放射断層撮像(PET撮像)を中心に、 各種画像検査、臨床症状および認知機能の評価を組み合わせて健常者と比較する。本研究により、PDE10Aの状態をもとにした統合失調症の病態解明および疾患層別化、将来的な新規治療法の確立につながることが期待される。
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Outline of Final Research Achievements |
Phosphodiesterase 10A (PDE10A) is a highly expressed enzyme in the basal ganglia, where cortical glutamatergic and midbrain dopaminergic inputs are integrated. We performed PET imaging with [18F]MNI-659, a specific PDE10A radioligand, to quantify PDE10A availabilities in in the limbic, executive, and sensorimotor striatal functional subregions, and in the pallidum. Multivariate analysis of covariance demonstrated a significant main effect of diagnosis on the PDE10A radioligand availabilities, indicating higher availabilities in the sensorimotor striatum in patients. The availabilities in this subregion were significantly and negatively correlated with the BACS Tower of London subtest scores in controls but not in patients. Glutamate levels assessed with MRS did not correlate significantly with the availabilities in either group. The results suggest altered striatal PDE10A availability and associated local neural dysfunctions in patients with schizophrenia.
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Academic Significance and Societal Importance of the Research Achievements |
PDE10Aはドーパミン制御機構を担う細胞内酵素であり、その阻害薬は統合失調症の創薬ターゲットの一つとなっている。しかしこれまで統合失調症患者の生体脳におけるPDE10Aの状態や分布を調べた研究はほとんど存在しなかった。本研究により、統合失調症の病態にPDE10Aの状態変化が関与することが示された。この結果は統合失調症の病態理解および統合失調症をはじめとする精神疾患の新規治療戦略構築に寄与すると考えられる。
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Report
(5 results)
Research Products
(24 results)
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[Journal Article] A first-in-human study of 11C-MTP38, a novel PET ligand for phosphodiesterase 72021
Author(s)
Kubota Manabu、Seki Chie、Kimura Yasuyuki、Takahata Keisuke、Shimada Hitoshi、Takado Yuhei、Matsuoka Kiwamu、Tagai Kenji、Sano Yasunori、Yamamoto Yasuharu、Okada Maki、Kikuchi Tatsuya、Ichise Masanori、Kawamura Kazunori、Zhang Ming-Rong、Higuchi Makoto
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Journal Title
European Journal of Nuclear Medicine and Molecular Imaging
Volume: 41
Issue: 11
Pages: 2928-2943
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] High-Contrast In Vivo Imaging of Tau Pathologies in Alzheimer’s and Non-Alzheimer’s Disease Tauopathies2021
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.
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Journal Title
Neuron
Volume: 109
Issue: 1
Pages: 42-58
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Positron emission tomography assessments of phosphodiesterase 10A in patients with schizophrenia2022
Author(s)
Manabu Kubota, Keisuke Takahata, Kiwamu Matsuoka, Yasunori Sano, Yasuharu Yamamoto, Kenji Tagai, Ryosuke Tarumi, Hisaomi Suzuki, Shin Kurose, Shinichiro Nakajima, Hiroki Shiwaku, Chie Seki, Kazunori Kawamura, Ming-Rong Zhang, Hidehiko Takahashi, Yuhei Takado, Makoto Higuchi
Organizer
Annual meeting of Society for Neuroscience (Neuroscience 2022)
Related Report
Int'l Joint Research
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[Presentation] PETを用いた統合失調症患者におけるホスホジエステラーゼ10A(PDE10A)の評価2022
Author(s)
久保田学, 高畑圭輔, 松岡究, 佐野康徳, 山本保天, 互健二, 垂水良介, 鈴木寿臣, 黒瀬心, 中島振一郎, 塩飽裕紀, 関千江, 河村和紀, 張明栄, 髙橋英彦, 高堂裕平, 樋口真人
Organizer
第44回日本生物学的精神医学会年会・第32回日本臨床精神神経薬理学会年会・第52回日本神経精神薬理学会年会・第6回日本精神薬学会総会 4学会合同年会(BPCNPNPPP4学会合同年会)
Related Report
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[Presentation] A first-in-human study of [11C]MTP38, a novel PET ligand for phosphodiesterase 7.2021
Author(s)
Kubota M, Seki C, Kimura Y, Takahata K, Shimada H, Takado Y, Matsuoka K, Tagai K, Sano Y, Yamamoto Y, Kikuchi T, Ichise M, Kawamura K, Zhang MR, Higuchi M
Organizer
CINP 2021 Virtual World Congress; 2021
Related Report
Int'l Joint Research
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