The influence of autoimmune antibodies on psychiatric diseases
Project/Area Number |
16K10188
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Psychiatric science
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Research Institution | Okayama University |
Principal Investigator |
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Research Collaborator |
Sakamoto Shinji
Kawai Hiroki
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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Keywords | 抗NMDA受容体抗体脳炎 / 統合失調症 / 気分障害 / 抗体価と精神症状 / 神経発達障害 / プライマリーカルチャーニューロン / 免疫療法 / cell based assay法 / 自己免疫性脳炎 / 抗 NMDA 受容体抗体 / 臨床転帰 / 抗免疫療法 / 双極性障害 / Cell Based Assay |
Outline of Final Research Achievements |
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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Academic Significance and Societal Importance of the Research Achievements |
抗NMDA受容体抗体脳炎は抗体除去により予後良好であるが治療が遅れた場合など時に重篤となる。精神症状のみで精神疾患として慢性の経過をたどっている場合や妊婦が抗NMDA受容体抗体脳炎に罹患した際の胎児の場合、抗NMDA受容体抗体に神経細胞が長期間暴露されることで、神経発達に不可逆な影響を及ぼす可能性が示唆された。今後、抗NMDA受容体以外に対する自己抗体の検索も行っていく必要がある。精神疾患に対して、早期の免疫療法(ステロイドパルス療法、血漿交換療法、免疫グロブリン大量療法、リツキシマブによる抗腫瘍療法)が有効である可能性が示唆された。
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Report
(4 results)
Research Products
(31 results)
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[Journal Article] Genome-Wide Association Study Detected Novel Susceptibility Genes for Schizophrenia and Shared Trans-Populations/Diseases Genetic Effect2019
Author(s)
Ikeda M,Takahashi A,Kamatani Y,Momozawa Y,Saito T,Kondo K,Shimasaki A,Kawase K,Sakusabe T,Iwayama Y,Toyota T,Wakuda T,Kikuchi M,Kanahara N,Yamamori H,Yasuda Y,Watanabe Y,Hoya S,Aleksic B,Kushima I,Arai H,Takaki M,Hattori K,Kunugi H,Okahisa Y,Ohnuma T,Ozaki N,Someya T,Hashimoto R,Yoshikawa T,Kubo M,Iwata N
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Journal Title
Schizophr Bull
Volume: 印刷中
Pages: 824-834
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Effects of the antipsychotics haloperidol, clozapine, and aripiprazole on the dendritic spine.2018
Author(s)
Takaki M, Kodama M, Mizuki Y, Kawai H, Yoshimura B, Kishimoto M, Sakamoto S, Okahisa Y, Yamada N.
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Journal Title
Eur Neuropsychopharmacol.
Volume: 28(5)
Pages: 610-619
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] 精神医学のフロンティア 統合失調症患者における認知機能障害の推定 多施設共同研究2018
Author(s)
藤野 陽生, 住吉 チカ, 安田 由華, 山森 英長, 藤本 美智子, 福永 雅喜, 三浦 健一郎, 竹林 佑人, 岡田 直大, 磯村 周一, 河野 直子, 豊巻 敦人, 久我 弘典, 磯部 昌憲, 大矢 一登, 岡久 祐子, 高木 学, 橋本 直樹, 加藤 正樹, 鬼塚 俊明, 上野 雄文, 大沼 徹, 笠井 清登, 尾崎 紀夫, 住吉 太幹, 井村 修, 橋本 亮太, COCORO
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Journal Title
精神経誌
Volume: 120
Pages: 255-261
Related Report
Peer Reviewed / Open Access
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[Journal Article] Estimated cognitive decline in patients with schizophrenia: A multicenter study.2017
Author(s)
Fujino H, Sumiyoshi C, Yasuda Y, Yamamori H, Fujimoto M, Fukunaga M, Miura K, Takebayashi Y, Okada N, Isomura S, Kawano N, Toyomaki A, Kuga H, Isobe M, Oya K, Okahisa Y, Takaki M, Hashimoto N, Kato M, Onitsuka T, Ueno T, Ohnuma T, Kasai K, Ozaki N, Sumiyoshi T, Imura O, Hashimoto R
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Journal Title
Psychiatry and Clinical Neurosciences
Volume: 印刷中
Pages: 294-300
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Individual risk alleles of susceptibility to schizophrenia are associated with poor clinical and social outcomes.2016
Author(s)
Sakamoto S, Takaki M, Okahisa Y, Mizuki Y, Inagaki M, Ujike H, Mitsuhashi T, Takao S, Ikeda M, Uchitomi Y, Iwata N, Yamada N.
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Journal Title
J Hum Genet.
Volume: 61
Pages: 329-334
DOI
NAID
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Pharmacogenomic Study of Clozapine-Induced Agranulocytosis/Granulocytopenia in a Japanese Population2016
Author(s)
Saito T, Ikeda M, Mushiroda T, Ozeki T, Kondo K, Shimasaki A, Kawase K, Hashimoto S, Yamamori H, Yasuda Y, Fujimoto M et al
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Journal Title
BIol Psychiatry
Volume: in press
Pages: 636-42
DOI
NAID
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] Effects of the antipsychotics haloperidol, clozapine, and aripiprazole on the dendritic spine2018
Author(s)
Takaki M, Kodama M, Mizuki Y, Kawai H, Yoshimura B, Kishimoto M, Sakamoto S, Okahisa Y, Yamada N.
Organizer
CINP 31st World Congress, Vienna, Austria
Related Report
Int'l Joint Research
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[Presentation] Effects of the antipsychotics haloperidol, clozapine, and aripiprazole on the dendritic spine2018
Author(s)
Takaki M, Kodama M, Mizuki Y, Kawai H, Yoshimura B, Kishimoto M, Sakamoto S, Okahisa Y, Yamada N.
Organizer
WFSBP Asia Pacific Regional Congress of Biological Psychiatry, WFSBP 2018 KOBE, Kobe, Japan
Related Report
Int'l Joint Research
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