Uchida, Hiroyuki

写真a

Affiliation

School of Medicine, Department of Neuropsychiatry (Shinanomachi)

Position

Professor
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Books 【 Display / hide 】

  • Encyclopedia of Psychopharmacology

    Uchida Hiroyuki, 2010

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Papers 【 Display / hide 】

  • Risk of falls associated with non-GABAergic hypnotics and benzodiazepines in hospitalized patients

    Shishida K., Nishimura W., Shimomura Y., Murayama M., Yoshimura K., Uchida H., Mimura M., Takeuchi H.

    General Hospital Psychiatry 94   10 - 15 2025.05

    ISSN  01638343

    　View Summary

    Objective: Non-GABAergic hypnotics introduced into clinical practice within the last two decades are pharmacologically presumed to have a lower risk of falls, but clinical investigations are scarce. We aimed to evaluate the risk of falls associated with different classes of hypnotics, namely benzodiazepines, ramelteon, suvorexant, and trazodone, in hospitalized individuals at a general hospital. Method: In this retrospective cohort study, data on the incidence of falls, hypnotic use, age, sex, body mass index (BMI), activities of daily living (ADL) score, presence of surgery, emergency admission, and ambulance use were collected for hospitalized patients aged 20 years or older who had been discharged from a tertiary general hospital in Japan between April 1, 2014, and March 31, 2019. The Cox proportional hazards model was used to examine factors associated with falls, adjusting for other demographics as covariates. Results: Among 28,029 patients, 383 falls occurred in 322 patients. Ramelteon or suvorexant was not associated with an elevated incidence of falls (adjusted hazard ratio [aHR], 0.78; 95 % CI, 0.34 to 1.81 and 0.44; 95 % CI, 0.13–1.46, respectively), in contrast to benzodiazepines (aHR, 2.17; 95 % CI 1.67–2.83) or trazodone (aHR, 1.96; 95 % CI 1.25–3.07). Advanced age, lower BMI, wheelchair dependency, non-surgical status, absence of emergency admissions, and ambulance use were also associated with the elevated incidence of falls. Conclusions: In hospitalized patients at general hospitals, ramelteon and suvorexant may not increase the risk of falls, while the use of benzodiazepines and trazodone requires careful attention to minimize this risk.

  • Characterization of patients with major psychiatric disorders with AMPA receptor positron emission tomography

    Hatano M., Nakajima W., Tani H., Uchida H., Miyazaki T., Arisawa T., Takada Y., Tsugawa S., Sano A., Nakano K., Eiro T., Abe H., Suda A., Asami T., Hishimoto A., Nagai N., Koizumi T., Nakajima S., Kurokawa S., Ohtani Y., Takahashi K., Kikuchi Y., Yatomi T., Honda S., Jinzaki M., Hirano Y., Mitoma R., Tamura S., Baba S., Togao O., Kosaka H., Okazawa H., Kimura Y., Mimura M., Takahashi T.

    Molecular Psychiatry 30 ( 5 ) 1780 - 1790 2025.05

    ISSN  13594184

    　View Summary

    Synaptic phenotypes in living patients with psychiatric disorders are poorly characterized. Excitatory glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) is a fundamental component for neurotransmission. We recently developed a positron emission tomography (PET) tracer for AMPAR, [11C]K-2, the first technology to visualize and quantify AMPARs density in living human brain. In this study, we characterized patients with major psychiatric disorders with [11C]K-2. One hundred forty-nine patients with psychiatric disorders (schizophrenia, n = 42; bipolar disorder, n = 37; depression, n = 35; and autism spectrum disorder, n = 35) and 70 healthy participants underwent a PET scan with [11C]K-2 for measurement of AMPAR density. We detected brain regions that showed correlation between AMPAR density and symptomatology scores in each of four disorders. We also found brain areas with significant differences in AMPAR density between patients with each psychiatric disorder and healthy participants. Some of these areas were observed across diseases, indicating that these are commonly affected areas throughout psychiatric disorders. Schizophrenia, bipolar disorder, depression, and autism spectrum disorder are uniquely characterized by AMPAR distribution patterns. Our approach to psychiatric disorders using [11C]K-2 can elucidate the biological mechanisms across diseases and pave the way to develop novel diagnostics and therapeutics based on the synapse physiology.

  • INTEGRATE: international guidelines for the algorithmic treatment of schizophrenia

    McCutcheon R.A., Pillinger T., Varvari I., Halstead S., Ayinde O.O., Crossley N.A., Correll C.U., Hahn M., Howes O.D., Kane J.M., Kabir T., Konradsson-Geuken Å., Lennox B., Hui C.L.M., Rossell S.L., Solmi M., Sommer I.E., Taipale H., Uchida H., Venkatasubramanian G., Warren N., Agid O., Arango C., de Bartolomeis A., Bittner R.A., Bressan R.A., Buchanan R.W., Cecere G., Chen E.Y.H., Citrome L., Dollfus S., Dursun S.M., Ebdrup B.H., Elkis H., Emsley R., Fernandez-Egea E., Fleischhacker W., Freudenreich O., Gadelha A., Gangadin S.S., Gaughran F., Hallak J.E.C., Hasan A., Homan P., Jauhar S., Kaiser S., Kwon J.S., Lee J., Leucht S., Libiger J., Leweke M.F., MacCabe J.H., Marder S.R., Marques T.R., Melle I., Mucci A., Nakajima S., O'Donoghue B., Ojagbemi A., Perry B.I., Roos J.L., Rubio J.M., Rybakowski J.K., Sachs G., Siu C.O., Suzuki T., Taylor D.M., Takeuchi H., Thirthalli J., Thomas N., Üçok A., Varambally S., Vasiliu O., Wagner E., Siskind D.

    The Lancet Psychiatry 12 ( 5 ) 384 - 394 2025.05

    ISSN  22150366

    　View Summary

    Schizophrenia is a mental illness involving multiple symptom domains and is often associated with substantial physical health comorbidities. Guidelines exist, but these tend to be country-specific and are often missing a concise yet comprehensive algorithmic approach. From May 1, 2023, to Jan 1, 2025, International Guidelines for Algorithmic Treatment (INTEGRATE) authors from all UN regions collaborated to develop a consensus guideline focused on the pharmacological treatment of schizophrenia. Following an umbrella review of the literature, input from expert workshops, a consensus survey, and lived experience focus groups, a consensus algorithmic guideline and associated digital tool were developed. Key recommendations include a focus on metabolic health from treatment initiation, timely assessment and management of non-response, symptom domain-specific interventions, mitigation of side-effects, and the prompt use of clozapine in cases of treatment resistance.

  • Prediction of postoperative delirium by blood metabolome analysis

    Arai N., Sugiura Y., Nakajima S., Wada M., Moriyama S., Mimura Y., Niinomi K., Takayama K., Maeda R., Kitada S., Fagarasan S., Tajima M., Boku S., Takebayashi M., Kato J., Kitago M., Kitagawa Y., Takahashi T., Shimizu H., Uchida H., Suematsu M., Mimura M., Noda Y.

    Journal of Psychiatric Research 184   500 - 514 2025.04

    ISSN  00223956

    　View Summary

    No established blood markers can preoperatively predict postoperative delirium. Blood concentrations of amino acid catabolites and dipeptides, including those secreted extracellularly during T-lymphocyte activation, were investigated as predictors of postoperative delirium using metabolomic analyses to ascertain whether preoperative blood metabolites could predict postoperative delirium. Eighteen and 24 participants were included in the delirium and non-delirium groups, respectively. Higher preoperative levels of amino acid (tryptophan) catabolites, via the indoleamine 2,3-dioxygenase pathway, were observed in the delirium group and identified as potential predictors of postoperative delirium in this study. The delirium group had preoperatively elevated levels of tryptophan catabolites and only a limited increase postoperatively, suggesting that the tryptophan catabolic pathway may be activated preoperatively in patients at high risk of delirium. Non-targeted metabolomic analysis found a set of preoperatively elevated γ-glutamyl dipeptides as potential predictors of postoperative delirium. In vitro experiments showed that T-cell-receptor stimulation increases tryptophan metabolism and specific γ-glutamyl dipeptide secretion, offering a possible explanation for the increased levels of metabolites in postoperative delirium. This study showed that levels of amino acid metabolites associated with blood immune activity may have the potential to predict postoperative delirium.

  • Abnormal neuritic microstructures in the anterior limb of internal capsules in treatment-resistant depression - A cross-sectional NODDI study

    Takahashi K., Noda Y., Hondo N., Shibukawa S., Kamagata K., Wada M., Honda S., Homma S., Tsukazaki A., Tsugawa S., Tobari Y., Moriyama S., Taniguchi K., Koike S., Cassidy C., Mimura M., Uchida H., Nakajima S.

    Journal of Psychiatric Research 183   93 - 99 2025.03

    ISSN  00223956

    　View Summary

    Background: Microstructural deficits of brain tissue are implicated in the pathophysiology of major depressive disorder (MDD). Recent studies have highlighted the neurotrophic mechanisms underlying effective treatments such as ketamine for treatment-resistant depression (TRD). However, little is known about microstructural changes in TRD. Neurite orientation dispersion and density imaging (NODDI) has enabled in vivo investigation of gray matter (GM) and white matter (WM) microstructure. This study sought to examine microstructural abnormalities in gray and white matter in patients with TRD using NODDI. Methods: This study compared the neurite density index (NDI) and orientation dispersion index (ODI) of neurites in 70 patients with TRD and 35 healthy controls. We fitted separate optimal NODDI models for gray and white matter. The locations of microstructural deficit were identified using region-based and voxel-based analysis. The affected white matter fibers were tracked with correlational tractography analysis. Results: An increase of ODI at the middle to the ventral part of the right anterior limb of the internal capsule (ALIC) was observed in patients with TRD compared with healthy controls. The quantitative anisotropy of frontothalamic fibers passing through the ALIC negatively correlated with the ODI increase in the TRD group. Conclusion: The microstructural disorganization of the frontothalamic pathway could be linked to the pathophysiology and individual heterogeneity of TRD.

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Papers, etc., Registered in KOARA 【 Display / hide 】

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Reviews, Commentaries, etc. 【 Display / hide 】

  • 精神展開剤シロシビンによるうつ病治療

    内田 裕之

    精神科治療学 ((株)星和書店)  40 ( 2 ) 221 - 224 2025.02

    ISSN  0912-1862

  • 自閉症スペクトラムとの鑑別に難渋した初回エピソード統合失調症の1例

    小野 瑛之介, 谷 英明, 木村 真奈美, 前田 貴記, 内田 裕之

    精神神経学雑誌 ((公社)日本精神神経学会)  126 ( 12 ) 830 - 830 2024.12

    ISSN  0033-2658

  • 安静脳波マイクロステート解析による統合失調症の神経生理基盤の解明

    谷口 敬太, 金子 直嗣, 和田 真孝, 垂水 良介, 高野 万由子, 本多 栞, 中島 振一郎, 三村 將, 内田 裕之, 野田 賀大

    臨床神経生理学 ((一社)日本臨床神経生理学会)  52 ( 5 ) 618 - 618 2024.10

    ISSN  1345-7101

  • Relapse of Tardive Dyskinesia Following Successful Treatment with Amantadine: A Case Report

    Kusudo K., Uchida H., Okada Y., Yoshida K.

    Journal of Clinical Psychopharmacology 44 ( 4 ) 424 - 425 2024.07

    ISSN  02710749

  • 精神・神経臨床における脳核医学画像:臨床の基本から最新の進歩まで　精神神経疾患におけるPETを用いた病態可視化技術の開発と展望

    高畑 圭輔, 森口 翔, 黒瀬 心, 市橋 雅典, 鈴木 寿臣, 互 健二, 遠藤 浩信, 久保田 学, 山本 保天, 三村 將, 徳田 隆彦, 内田 裕之, 樋口 真人

    精神神経学雑誌 ((公社)日本精神神経学会)   ( 2024特別号 ) S522 - S522 2024.06

    ISSN  0033-2658

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Presentations 【 Display / hide 】

  • 処方変更後のリスペリドン血中濃度を予測する試み: Population Pharmacokineticsを用いて

    Uchida Hiroyuki

    第20回日本臨床精神薬理学会 (仙台) , 

    2010
    , 

    Poster presentation

  • Effects of discontinuing benzodiazepine-derivative hypnotics on cognitive and motor functions in the elderly.

    Uchida Hiroyuki

    American Association for Geriatric Psychiatry (Savannah) , 

    2010
    , 

    Poster presentation

  • Clozapine and global cognition in schizophrenia.

    Tarek RajjiUchida Hiroyuki

    American Association for Geriatric Psychiatry (Savannah) , 

    2010
    , 

    Poster presentation

  • Low dose versus standard dose of antipsychotics for relapse prevention in schizophrenia: a meta-analysis

    Uchida Hiroyuki

    2nd International Schizophrenia Research Society (Florence) , 

    2010
    , 

    Poster presentation

  • 抗うつ薬の変更はどのタイミングで行うべきか？ 無作為割り付け前向き試験

    Uchida Hiroyuki

    第20回日本臨床精神薬理学会 (仙台) , 

    2010
    , 

    Poster presentation

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

  • Elucidating mechanisms of antidepressant effects of ketamine for treatment-resistant depression: an AMPA PET study

    2022.04
    -
    2025.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 基盤研究(B), Principal investigator

  • Analysis of inappropriate use of psychotropics, and cohort study of suicide attempts including overdose and transition of the elderly psychiatric diagnoses

    2021.04
    -
    2022.03

    Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), No Setting

    　View Summary

    第一に、向精神薬の不適切使用に関する実態を、本邦において厚生労働省から提供されるレセプト情報・特定健診等情報データベース（NDB）の解析により明らかにする。第二に、過量服薬や自殺の転帰と向精神薬の使用に関する関連を、NDBや海外のデータベースから経時的なデータを抽出し、経時的変化を追う解析及び横断面の解析を行い明らかにする。第三に、NDBや海外のデータベースから抗てんかん薬の使用と認知症発症の関連を、向精神薬の処方と診断名等の変遷を縦断的に解析することにより明らかにし、てんかんを有することによる認知症発症のリスクの一端を解明する。
    向精神薬と身体疾患薬の併用に関する実態把握は十分に行われていなかった。今回、我々は厚生労働省から得たレセプト情報・特定健診等情報データベース（NDB）から得た2015年1月における58万1990人のデータにつき、炭酸リチウム服用患者、選択的セロトニン再取り込み阻害薬（SSRI）/　セロトニン-ノルアドレナリン再取り込み阻害薬（SNRI）服用患者、ミルタザピン服用患者、について各々非服用者を対象に身体疾患薬の処方率の比較をFisher's exact testを用いて行う、等の解析を施行した。その結果、NSAIDs、利尿薬、ACE阻害薬、ARBの処方率は、炭酸リチウム服用患者が非服用患者に比して、有意に低く(18.3%(235人/1284人) VS 31.9%(409人/1284人)、p=7.6×10^(-10))、NSAIDs、抗血栓薬の処方率はSSRI/SNRI服用患者と非服用患者において同等であり（23.1%(3078人/13330人) VS 24.1%（3219人/13330人)、p=0.044)、ワーファリン処方率はミルタザピン服用患者が非服用者に比して有意に低かった（0.78%(18人/2300人) VS 1.65%（38人/2300人)、p=0.01)こと等がわかり、各々の向精神薬服用中患者の相当数が注意喚起を要する身体疾患の薬剤併用を受けている事を明らかにした（上記の解析では、全てBonferroniの補正を行い、p＜0.05/3を統計的に有意な差があるものとした。）。精神科医、身体科の医師への服薬併用注意を強く喚起し、薬物治療の安全性を高める上で極めて重要な成果であり、今後もビッグデータから現場の処方実態を捉え直すことが望まれる。なお本研究成果は、7th Congress of AsCNP2021にて口頭発表予定であり、研究期間中に論文投稿を開始している。

  • Development of pre-morbid diagnostic marker of schizophrenia: AMPA PET study

    2020.07
    -
    2024.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Challenging Research (Pioneering), Principal investigator

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    統合失調症は早期発見・早期治療により、より良い予後が達成できる。精神病発症危険状態（At Risk Mental State [ARMS]）という、発病前ではあるものの今後の発病リスクの高い一群がある。ARMSのうち約30％が精神病（主に統合失調症）に移行するが、“移行者”を早期診断する方法はないため治療の遅れにつながっている。本研究では、統合失調症と関連の深いAMPA受容体をPET検査により測定し、統合失調症に移行するARMS症例、移行しないARMS症例の両者を比較し、今後の診断に役立てる。

  • AMPA受容体に注目した統合失調症の病態解明：世界初AMPA受容体PET研究

    2019.04
    -
    2022.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), Principal investigator

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    統合失調症の原因解明は停滞しており、斬新な視点による研究が緊急課題である。グルタミン神経系のAMPA受容体は、動物研究により統合失調症の発病への関与が明らかになっているが、ヒトのデータはなかった。そこで本研究では、統合失調症患者の脳内のAMPA受容体密度を、陽電子放射断層撮影（PET)検査により測定し、AMPA受容体が統合失調症の発病にいかに関連しているか解明する。

  • 唾液メタボロームマッピング解析を用いた精神疾患の病態解明および臨床応用法の開発

    2019.04
    -
    2022.03

    Kanagawa Dental College, Grant-in-Aid for Scientific Research (C), No Setting

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    近年、複雑な社会環境により精神疾患に罹患した歯科受診患者が急増している。しかしながら、精神疾患の病態は複雑で、未だ原因が解明されていないのが現状である。また精神疾患の診断法は、問診や臨床症状を基にした主観的な診断が主体であるが、病態が複雑であることから診断の客観的評価法の確立が必須である。さらに再発が多いことから、予防、早期発見および予後管理を行うことが喫緊の課題である。本研究は、唾液の代謝産物から精神疾患の病態を解明し、さらに精神疾患の予防、早期発見、診断として利用できるように簡易検出系の開発を行い、ヒトで臨床応用することを最終目標とする。

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Awards 【 Display / hide 】

  • Journal of Clinical Psychopharmacology, Top Reviewers of 2024

    2025.04

    Type of Award： Honored in official journal of a scientific society, scientific journal

  • 日本臨床精神神経薬理学会　ポールヤンセン賞

    2024.05

    Type of Award： Award from Japanese society, conference, symposium, etc.

  • Journal of Clinical Psychopharmacology, Top Reviewers of 2023

    2024.04

    Type of Award： Honored in official journal of a scientific society, scientific journal

  • Journal of Clinical Psychopharmacology, Top Reviewers of 2022

    2023.04

  • 日本臨床精神神経薬理学会　ポールヤンセン賞

    2022.11

    Type of Award： Award from Japanese society, conference, symposium, etc.

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Courses Taught 【 Display / hide 】

  • PSYCHIATRY: SEMINAR

    2025

  • PSYCHIATRY: PRACTICE

    2025

  • PSYCHIATRY

    2025

  • PSYCHIATRIC PALLIATIVE CARE MEDICINE: SEMINAR

    2025

  • PSYCHIATRIC PALLIATIVE CARE MEDICINE: PRACTICE

    2025

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