Updated on 2025/05/01

写真a

 
TAKAKI Manabu
 
Organization
Faculty of Medicine, Dentistry and Pharmaceutical Sciences Professor
Position
Professor
Homepage
http://kaken.nii.ac.jp/d/r/60452570.ja.html
Profile
精神医学において統合失調症の臨床、基礎研究を行ってきました。最近は、自己免疫性脳炎と精神疾患の関連を中心に臨床、基礎研究を行っています。加えて、精神科薬理学の臨床と基礎の論文を執筆しています。
External link

Degree

  • 医学博士

Research Interests

  • 精神科薬理学

  • 包括脳ネットワーク

  • 自己免疫性脳炎

  • 抗NMDAR抗体

  • 神経発達障害

  • シナプス

  • 統合失調症

  • PCM-1

  • DISC-1

  • 認知機能

  • クロザピン

  • セントロソーム

  • カリリン

Research Areas

  • Life Science / Psychiatry

Research History

  • 岡山大学学術研究院 医歯薬学域   教授

    2022.10

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Papers

  • Olanzapine enabled rechallenge after lorlatinib-induced psychosis: A case report. International journal

    Akiyoshi Yokode, Masaki Fujiwara, Yuko Nakamura, Kadoaki Ohashi, Shinji Sakamoto, Manabu Takaki

    PCN reports : psychiatry and clinical neurosciences   4 ( 2 )   e70091   2025.6

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    Language：English   Publishing type：Research paper (scientific journal)  

    BACKGROUND: Lorlatinib is a third-generation tyrosine kinase inhibitor for anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). While it has a high intracranial lesion control rate, it can also cause central nervous system complications, including psychotic symptoms. We present a case of lorlatinib-induced psychosis successfully managed with olanzapine, enabling lorlatinib rechallenge. CASE PRESENTATION: A 32-year-old woman with ALK-positive NSCLC and brain metastases was started on lorlatinib. After 18 months, she developed hallucinations and delusions. Despite treatment with risperidone, her psychotic symptoms persisted, leading to hospitalization. Her symptoms resolved upon lorlatinib discontinuation while risperidone was continued. Given the critical role of lorlatinib in controlling brain metastases, rechallenge was considered. To mitigate concerns regarding drug interactions, risperidone was replaced with olanzapine. Following lorlatinib rechallenge with olanzapine, no recurrence of psychiatric symptoms was observed, allowing continued lorlatinib treatment. Additionally, no progression of lung cancer was noted. CONCLUSION: Lorlatinib is an essential drug for controlling brain metastases in ALK-positive NSCLC. However, it can induce psychotic symptoms. When psychiatrists are involved in managing adverse effects during cancer treatment, close collaboration among oncologists, psychiatrists, and patients is essential.

    DOI： 10.1002/pcn5.70091

    PubMed

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  • A case report of ineffective electroconvulsive therapy for chronic pain. International journal

    Takashi Fukao, Masaki Fujiwara, Yuto Yamada, Kazushi Asada, Takahiro Asada, Hirotoshi Ri, Shinji Sakamoto, Manabu Takaki

    PCN reports : psychiatry and clinical neurosciences   4 ( 2 )   e70108   2025.6

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    Language：English   Publishing type：Research paper (scientific journal)  

    BACKGROUND: Somatic symptom disorder (SSD), which includes chronic pain, is a common mental disorder characterized by significant functional impairment and other psychiatric comorbidities. Electroconvulsive therapy (ECT) has been proposed as a potential treatment for refractory chronic pain. However, evidence supporting its efficacy is limited and/or low quality. We present a case of SSD with chronic pain in which ECT was ineffective. CASE PRESENTATION: The patient was a 63-year-old man with chronic pain in the lower back, buttocks, thighs, and soles of the feet. The duration of his chronic pain was 3.8 years. He was diagnosed with Bertolotti's syndrome and SSD. He did not meet the criteria for major depressive disorder. He kept physically active by walking and doing exercises to distract himself from his pain. He strongly perceived pain as a physical issue and preferred ECT over psychotherapy. Despite undergoing 10 ECT sessions with adequate seizures, his pain persisted. After four sessions, he experienced despair over the lack of improvement in pain, which temporarily intensified his suicidal ideation. After undergoing ECT, he continued to maintain his activities, including walking and exercise, while his catastrophic thinking about pain persisted. CONCLUSION: The ineffectiveness of ECT in this case highlights the need for balanced counseling, particularly for patients who consider ECT a last-resort treatment. Psychological monitoring and depression screening are essential, especially given the risk of heightened despair or suicidal ideation when ECT is ineffective. Therefore, collaborative decision-making based on accurate information is vital.

    DOI： 10.1002/pcn5.70108

    PubMed

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  • Cerebral Braak stage and amygdala granular fuzzy astrocyte status have independent effects on neuronal 3R-tau and 4R-tau accumulations in the olfactory bulb, respectively, in cases with low to intermediate AD neuropathologic change. International journal

    Osamu Yokota, Tomoko Miki, Hanae Nakashima-Yasuda, Hideki Ishizu, Takashi Haraguchi, Akinori Miyashita, Takeshi Ikeuchi, Masato Hasegawa, Naoto Nishikawa, Shintaro Takenoshita, Seishi Terada, Manabu Takaki

    Acta neuropathologica   149 ( 1 )   36 - 36   2025.4

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  • Successful retreatment with clozapine combined with ursodeoxycholic acid after clozapine-induced hepatitis: A case report

    Ryota Sato, Yuto Yamada, Masaki Fujiwara, Yuji Yada, Yoshiki Kishi, Manabu Takaki

    Asian Journal of Psychiatry   102   104260 - 104260   2024.12

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    Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

    DOI： 10.1016/j.ajp.2024.104260

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  • Doctor Interview 自己免疫性脳炎などの適切な診断により,難治の疾患を治療可能な疾患に

    髙木 学

    精神科臨床legato / 「精神科臨床legato」編集委員会 編   10 ( 2 )   120 - 123   2024.8

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    Language：Japanese   Publisher：大阪 : メディカルレビュー社  

    CiNii Books

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    Other Link： https://ndlsearch.ndl.go.jp/books/R000000004-I033689943

  • 経ストーマ投与されたジアゼパム坐剤が自然排出されていたために、離脱症状を生じた1例

    山田 裕士, 藤原 雅樹, 鳥越 美沙子, 高木 学

    精神神経学雑誌   ( 2024特別号 )   S406 - S406   2024.6

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    Language：Japanese   Publisher：(公社)日本精神神経学会  

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  • 【抗体介在性自己免疫性脳炎と精神医学】自己免疫性精神病 岡山大学病院における知見を含めて Invited Reviewed

    高木 学, 岡久 祐子, 酒本 真次, 樋之津 健二, 河合 弘樹, 来住 由樹, 山田 了士

    精神神経学雑誌   126 ( 2 )   114 - 125   2024.2

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    Authorship：Lead author   Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(公社)日本精神神経学会  

    自己免疫性脳炎の存在は,『8年越しの花嫁』『Brain on Fire(脳に棲む魔物)』にて書籍,映画化され,広く知られるようになった.抗NMDAR脳炎は,比較的若年女性に多く,原因となる神経自己抗体のなかで最多頻度であり,次に頻度が高い抗VGKC複合体抗体脳炎は,比較的高齢男性に多い.近年,これら以外にも,精神疾患の病態に関与する神経伝達物質受容体抗体が次々と発見され,検出可能となってきている.さらに,内因性精神病と診断される患者の検討は,血清で行われていたため批判も多かったが,髄液内の神経自己抗体の存在を示唆する報告も増えており,精神疾患の新たな治療法として免疫療法への期待が高まっている.神経細胞膜または核内自己抗体によって,精神症状のみを呈する(神経症状を全く,または微細にしか認めない)患者群は,典型的な自己免疫性脳炎とは区別して,自己免疫性精神病(AP)と呼ばれる.しかし,脳神経内科領域における「自己免疫性脳炎」と精神科領域における「自己免疫性精神病」は概念の違いが大きく,さまざまな診断基準,検体(血清,髄液)の違い,抗体検査法の違いのために,依然として「自己免疫性脳炎」に保険適用がある検査や治療法はない.抗NMDAR脳炎は,早期発見による早期治療介入が有効であり,治療の遅れは予後不良と関係する.そこで,統合失調症,気分障害,てんかん,睡眠障害などさまざまな精神疾患の鑑別診断としてAPを考える必要がある.神経自己抗体を検出し免疫療法の根拠となる確定診断を行うことは重要であるが,実臨床では,確定診断に至らなくともprobable診断のみで免疫療法の積極的な検討が必要となる.本稿では,岡山大学病院での経験症例を交えながら,APの臨床症状,診断,検査法,検査所見,病態機序,治療と予後,精神疾患患者で多くみられる血清抗体の意味を解説し,本分野の将来の展望を考察する.(著者抄録)

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  • ダウン症のある人に生じた急激な生活機能変化の調査

    竹之下 慎太郎, 上地 玲子, 桑野 良三, 井上 友和, 黒住 卓, 楢原 幸二, 末光 茂, 西川 直人, 林 聡, 寺田 整司, 高木 学

    日本発達障害学会研究大会発表論文集   58回   130 - 130   2023.11

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    Language：Japanese   Publisher：(一社)日本発達障害学会  

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  • ダウン症候群における認知症の有病率と危険因子

    竹之下 慎太郎, 寺田 整司, 井上 友和, 黒住 卓, 西川 直人, 三木 知子, 横田 修, 高木 学, 末光 茂, 桑野 良三

    老年精神医学雑誌   34 ( 増刊II )   222 - 222   2023.10

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    Language：Japanese   Publisher：(株)ワールドプランニング  

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  • 相貌認知障害と左無視を呈し皮下質諸核に4リピートタウ蓄積を有したPick病の一例

    三木 知子, 横田 修, 石津 秀樹, 安田 華枝, 原口 俊, 竹之下 慎太郎, 寺田 整司, 高木 学

    老年精神医学雑誌   34 ( 増刊II )   210 - 210   2023.10

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    Language：Japanese   Publisher：(株)ワールドプランニング  

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  • 認知症患者の主観的QOLの予測 認知症外来における縦断研究

    西川 直人, 竹之下 慎太郎, 寺田 整司, 三木 知子, 横田 修, 林 聡, 矢部 真弓, 今井 奈緒, 堀内 真希子, 高木 学

    老年精神医学雑誌   34 ( 増刊II )   195 - 195   2023.10

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    Language：Japanese   Publisher：(株)ワールドプランニング  

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  • ダウン症候群を持つ施設入所者における認知症有病率の横断調査

    竹之下 慎太郎, 寺田 整司, 井上 友和, 黒住 卓, 西川 直人, 三木 知子, 横田 修, 高木 学, 末光 茂, 桑野 良三

    Dementia Japan   37 ( 4 )   683 - 683   2023.10

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    Language：Japanese   Publisher：(一社)日本認知症学会  

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  • 認知症患者のおける主観的QOLの予測因子

    西川 直人, 竹之下 慎太郎, 寺田 整司, 三木 知子, 横田 修, 林 聡, 矢部 真弓, 今井 奈緒, 堀内 真希子, 高木 学

    Dementia Japan   37 ( 4 )   671 - 671   2023.10

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    Language：Japanese   Publisher：(一社)日本認知症学会  

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  • 岡山大学病院におけるケタミンを使用したECT9例の検討

    馬場 悠花里, 山田 裕士, 酒本 真次, 竹之下 慎太郎, 寺田 整司, 高木 学

    精神神経学雑誌   ( 2023特別号 )   S554 - S554   2023.6

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    Language：Japanese   Publisher：(公社)日本精神神経学会  

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Books

  • 自己免疫性脳炎・関連疾患ハンドブック = Handbook of Autoimmune Encephalitis and Related Disorders

    下畑, 享良ら 高木学（ Role： Joint author）

    金芳堂  2023.5  （ ISBN:9784765319560 ）

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    Total pages：vii, 363p   Language：Japanese

    CiNii Books

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MISC

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Research Projects

  • Influence of neuronal autoantibodies to the onset and recurrence of psychosis

    Grant number：22K07616  2022.04 - 2025.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    高木 学

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    Grant amount：\4160000 （ Direct expense: \3200000 、 Indirect expense：\960000 ）

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  • Dimensional approach to mental disease through autoantibodies

    Grant number：19K08019  2019.04 - 2022.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Takaki Manabu

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    Grant amount：\4420000 （ Direct expense: \3400000 、 Indirect expense：\1020000 ）

    Anti-NMDA receptor antibodies were measured in about 260 patients with suspected schizophrenia, mood disorders, and epilepsy, and more than 10 were positive. The patient was ineffective with psychotropic medications and was in complete or partial remission with immunotherapy including rituximab. In eleven patients with epilepsy each two patient was positive for anti-NMDA receptor antibodies or VGKC complex antibodies (LGI-1 antibody), and in 3 patients, the symptoms including epilepsy were in complete or partial remission by immunotherapy. In a basic study using rat cerebral cortex primary culture neurons, patient anti-NMDA receptor antibodies impaired neurite outgrowth, delayed central body disappearance, and dendrite formation and were irreversible even if the antibodies were removed. Prolonged exposure to neurons of anti-NMDA receptor antibodies impaired neurodevelopment.

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  • 自閉症児に対する新しい療育RDI（対人関係発達指導法）の効果検証

    Grant number：17K10332  2017.04 - 2023.03

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    岸本 真希子, 高木 学

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    Grant amount：\4550000 （ Direct expense: \3500000 、 Indirect expense：\1050000 ）

    対人関係発達指導法（RDI）による介入を受けた9名のうち、ADOS-2にて自閉症と診断された8名の対象児において対象児の適応行動尺度、情緒、行動上の問題、養育者（母親）の育児ストレスや心理的ストレスなどについて評価を行い、介入前と介入1年後の改善度に関して解析を行った。
    主要評価尺度であるVineland-II適応行動尺度の適応行動総合点は有意に改善した（介入前：70.25±10.51 vs 介入後：79.62±16.19、p=0.034）。領域標準得点では、コミュニケーション（p=0.034）と日常生活スキル（p=0.208）に有意な改善は認められなかったが、社会性（介入前：56.62±14.26 vs 介入後：72.50±21.06、p=0.018）に有意な改善が認められた。さらに下位領域の中では、対人関係（介入前：9.12±2.16 vs 介入後：11.12±1.80、p=0.018）が有意に改善し、その他読み書き（p=0.068）、遊びと余暇（p=0.063）、コーピングスキル（p=0.059）に改善の傾向を認めた。しかしながら、異常行動チェックリスト日本語版(ABCーJ) の5つの下位尺度、子どもの強さと困難さアンケート（SDQ）における総合的困難さと5つの下位尺度のいずれにおいても介入前後で有意な改善は認められなかった。また育児ストレスに関する評価尺度である育児ストレスインデックス（PSI）では、親自身に関わるストレス項目や、子どもの特徴に関わるストレス項目のいずれにおいても有意な改善は認められなかった。さらに養育者（母親）心理的ストレス反応の尺度である心理的ストレス反応測定尺度（SRS-18）の3つの下位尺度において、いずれも介入前後で有意な改善は認められなかった。

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  • The influence of autoimmune antibodies on psychiatric diseases

    Grant number：16K10188  2016.04 - 2019.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Takaki Manabu, Sakamoto Shinji, Kawai Hiroki

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    Grant amount：\4550000 （ Direct expense: \3500000 、 Indirect expense：\1050000 ）

    The patients with anti-NMDA receptor encephalitis show only psychiatric symptoms before or without neurological findings. Anti-NMDA receptor antibodies is supposed to be involved in the pathogenesis of psychiatric disorders. The 190 patients with psychiatric disorders were tested anti-NMDA receptor antibodies by cell based assay. Seven patients with initially suspected schizophrenia and mood disorder had anti-NMDA receptor antibodies. The immunotherapy including methylprednisolone pulse, plasma exchange, intravenous immunoglobulin or rituximab were effective and the psychotropic medications were not. There was a correlation between anti-NMDA receptor antibody titers and psychiatric symptoms scored by Brief Psychiatric Rating Scale. In rat primary cerebral culture neurons, anti-NMDA receptor antibodies impaired neurite outgrowth, disappearance of centrosome (failure of neuronal migration), dendrite formation, and these phenotypes were not reversible even after removal of antibodies.

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  • Reclassification of schizophrenia by candidate gene and symptom

    Grant number：25461731  2013.04 - 2016.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Takaki Manabu

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    Grant amount：\5070000 （ Direct expense: \3900000 、 Indirect expense：\1170000 ）

    We investigated the association between genetics and clinical or social outcomes of about 500 patients with schizophrenia at the critical period. Among 7 SNPs of 6 genes (SLC6A5, DTNBP1, GRM7, PPP3CC, EGR3, and PDE4B) which participated in NMDA receptor function, rs894747 of SLC6A5 gene was related to severity of illness and social outcome. Rs472952 of PDE4B gene was related to low score of letter fluency test. In 91SNPs of GWAS analysis of Japanese patients with schizophrenia, each 3SNPs including rs2623659 of CSMD1 was related to severity of illness or social outcome. 3SNPs ralated with severity of illness was also related to treatment resistance. It is interesting that the genetic factor also influenced to the clinical or social outcomes of the patients with schizophrenia.

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  • The functionalanalysis of the Pericentriolar material 1 (PCM1), one of the candidate genes of schizophrenia at synapse

    Grant number：22791125  2010 - 2012

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Young Scientists (B)

    TAKAKI Manabu

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    Grant amount：\4030000 （ Direct expense: \3100000 、 Indirect expense：\930000 ）

    Four functional polymorphism of the pericentriolar material 1 (PCM1) gene is not associated with the schizophrenia in a Japanese population. The PCM1 protein expresses more in E17 than in adult. The PCM1 protein exists at centrosome until D.I.V. 7 days, diminishes until D.I.V. 14 days, and doesn’t exist on spine in D.I.V. 28 days. The period of expression and the distribution of PCM1 are same with r-tubulin. The human Rho guanine nucleotide exchange factor 11 (ARHGEF11) gene has been reported to be associated with type 2 diabetes mellitus (T2DM). Four polymorphism of ARHGEF11 which was reported to be associated with T2DM were also associated with the paranoid subtype of schizophrenia in a Japanese population. ARHGEF11 has co-localized with PSD95, one of the post synaptic marker. ARHGEF11 may be one of the genetic links between schizophrenia and T2DM and have integrated the synaptic morphology through the interaction withDisrupted-In-Schizophrenia-1 (DISC-1).

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  • Disrupted in Schizophrenia-1 (Disc-1), a candidate gene of schizophrenia regulates kalirin and maintains synapse.

    Grant number：20790840  2008 - 2009

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Young Scientists (B)

    TAKAKI Manabu

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    Grant amount：\4290000 （ Direct expense: \3300000 、 Indirect expense：\990000 ）

    Disrupted in Schizophrenia-1 (Disc-1) is a candidate gene of schizophrenia. Following to the development, Disc-1, dynein and BBS4, the binding protein of Disc-1 moved from centrosome to spine. On the other hand, r-tubulin and PCM-1 did not. Disc-1 regulates kalirin and maintains spine. Disc-1 inhibited the binding of Kalirin-7 and Rac1. Clozapine, one of the atypical psychotics, which is effective to intractable schizophrenia and related to NMDA receptor function, increased PSD95, a post synaptic marker.

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Class subject in charge

  • Neuropsychiatry (Core Clinical Practice) （2024academic year） special  - その他

  • Neuropsychiatry （2024academic year） Fourth semester  - 水6

  • Practicals: Neuropsychiatry （2024academic year） special  - その他

  • Research Project: Neuropsychiatry （2024academic year） special  - その他

  • Research Projects and Practicals: Neuropsychiatry I （2024academic year） special  - その他

  • Lecture and Research Projects: Neuropsychiatry I （2024academic year） special  - その他

  • Research Projects and Practicals: Neuropsychiatry II （2024academic year） special  - その他

  • Lecture and Research Projects: Neuropsychiatry II （2024academic year） special  - その他

  • Mental Disorder （2024academic year） special  - その他

  • Research Presentation in Neuroscience （2024academic year） special  - その他

  • Lecture : Elderly healthcare （2024academic year） special  - その他

  • Elective Clinical Practice (Neuropsychiatry) （2024academic year） special  - その他

  • Neuropsychiatry (Core Clinical Practice) （2023academic year） special  - その他

  • Neuropsychiatry （2023academic year） Fourth semester  - 水6

  • Practicals: Neuropsychiatry （2023academic year） special  - その他

  • Research Project: Neuropsychiatry （2023academic year） special  - その他

  • Research Projects and Practicals: Neuropsychiatry I （2023academic year） special  - その他

  • Lecture and Research Projects: Neuropsychiatry I （2023academic year） special  - その他

  • Research Projects and Practicals: Neuropsychiatry II （2023academic year） special  - その他

  • Lecture and Research Projects: Neuropsychiatry II （2023academic year） special  - その他

  • Mental Disorder （2023academic year） special  - その他

  • Lecture : Elderly healthcare （2023academic year） special  - その他

  • Elective Clinical Practice (Neuropsychiatry) （2023academic year） special  - その他

  • Neuropsychiatry (Core Clinical Practice) （2022academic year） special  - その他

  • Research Projects and Practicals: Neuropsychiatry I （2022academic year） special  - その他

  • Lecture and Research Projects: Neuropsychiatry I （2022academic year） special  - その他

  • Research Projects and Practicals: Neuropsychiatry II （2022academic year） special  - その他

  • Lecture and Research Projects: Neuropsychiatry II （2022academic year） special  - その他

  • Mental Disorder （2022academic year） special  - その他

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