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

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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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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

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