Dimensional approach to mental disease through autoantibodies
| Project/Area Number |
19K08019
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 52030:Psychiatry-related
|
|---|
| Research Institution | Okayama University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2019-04-01 – 2022-03-31
|
| Project Status |
Completed (Fiscal Year 2021)
|
| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
|---|
| Keywords | 自己免疫性脳炎 / 自己抗体 / 精神疾患 / 免疫療法 / 抗NMDA受容体抗体脳炎 / VGKC複合体抗体 / LGI-1抗体 / cell based assay法 / 抗NMDAR抗体脳炎 / 抗DRD2抗体脳炎 / 統合失調症 / 気分障害 / てんかん精神病 / 非定型精神病 / 神経発達障害 / 抗VGKC複合体抗体 / 抗NMDA受容体抗体 / ディメンジョナルアプローチ |
|---|
| Outline of Research at the Start |
精神疾患の病態仮説は、グルタミン酸、ドパミン、GABA仮説があり、各受容体への自己抗体が存在する。精神疾患と診断された患者の中に、抗NMDA受容体抗体の陽性例が増えているが、他の受容体抗体の検討はない。精神疾患の発症の原因として神経発達障害仮説があるが、我々は自己抗体が神経発達や精神疾患の発症脆弱性に与える影響の検討を世界で初めて行ってきた。本研究では、抗NMDA受容体抗体を含む神経伝達物質受容体自己抗体の、動物実験を用いた基礎的検討、患者髄液を用いた臨床的検討を行い、神経発達、臨床症状、治療効果の違いを検討し、精神疾患を神経伝達物質障害別に新分類するディメンジョナルアプローチに寄与する。
|
| Outline of Final Research Achievements |
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.
|
| Academic Significance and Societal Importance of the Research Achievements |
統合失調症、気分障害、てんかんなど初期診断される患者で神経自己抗体の存在が確認され、免疫療法の有効性が示唆された。抗NMDA受容体抗体脳炎は早期発見治療によって予後が良い疾患であるが、発見が遅れれば致死的または後遺症を生じる。今回の基礎的研究で抗NMDA受容体抗体の直接の神経発達障害が証明され、抗NMDA受容体抗体を含む各種神経自己抗体検査を積極的に行い、自己免疫性脳炎の典型的経過で致死的な症状を示す患者だけでなく、精神症状のみの抗体陽性者に対しても、発症早期や再発予防に免疫療法を行う根拠や、向精神薬抵抗性の難治で自己抗体が陽性の患者に免疫療法を積極的に行う可能性が示唆された。
|
Report
(4 results)
Research Products
(31 results)
-
-
-
[Journal Article] Impairment of early neuronal maturation in anti-NMDA-receptor encephalitis.2022
Author(s)
Okamoto S, Takaki M, Hinotsu K, Kawai H, Sakamoto S, Okahisa Y, Takao S, Tsutsui K, Kanbayashi T, Tanaka K, Yamada N.
-
Journal Title
Psychopharmacology (Berl).
Volume: 239
Pages: 525-531
DOI
Related Report
Peer Reviewed
-
-
-
-
-
[Journal Article] The relationship between plasma clozapine concentration and clinical outcome: a cross-sectional study.2021
Author(s)
Yada Y, Kitagawa K, Sakamoto S, Ozawa A, Nakada A, Kashiwagi H, Okahisa Y, Takao S, Takaki M, Kishi Y, Yamada N.
-
Journal Title
Acta Psychiatr Scand .
Volume: 143
Pages: 227-237
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
[Journal Article] Electroconvulsive Therapy Is Effective and Safe for Serious Catatonia-Related Ileus: Two Case Reports2020
Author(s)
Yuto Yamada, Masaki Fujiwara, Ryuhei So, Satoru Edahiro, Yukiko Matsui, Shinji Sakamoto, Kiyohiro Kawada, Manabu Takaki, Suguru Ishizu, Keiko Kanazawa, Yoshiki Kishi, Norihito Yamada
-
Journal Title
DOI
Related Report
Peer Reviewed
-
-
-
[Journal Article] Anti-NMDA-receptor antibody in initial diagnosis of mood disorder.2020
Author(s)
Kawai H, Takaki M, Sakamoto S, Shibata T, Tsuchida A, Yoshimura B, Yada Y, Matsumoto N, Sato K, Abe K, Okahisa Y, Kishi Y, Takao S, Tsutsui K, Kanbayashi T, Tanaka K, Yamada N.
-
Journal Title
Neuropsychiatr Dis Treat
Volume: 29(9)
Pages: 1041-1050
DOI
Related Report
Peer Reviewed
-
[Journal Article] Switching strategies for antipsychotic monotherapy in schizophrenia: a multi-center cohort study of aripiprazole2020
Author(s)
Obayashi Y, Mitsui S, Sakamoto S, Minao N, Yoshimura B, Kono T, Yada Y, Okahisa Y, Takao S, Kishi Y, Takeda T, Takaki M, Yamada N.
-
Journal Title
Psychopharmacology
Volume: 237(1)
Pages: 167-175
DOI
Related Report
Peer Reviewed
-
-
-
[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
-
Journal Title
Schizophr Bull
Volume: 印刷中
Pages: 824-834
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
-
[Presentation] 慢性統合失調症患者におけるアリピプラゾール単剤治療への切替方法についての検討（多施設コホート研究）2020
Author(s)
大林芳明, 光井 聡，酒本真次，皆尾 望, 吉村文太, 耕野敏樹, 矢田勇慈, 岡久祐子, 高尾総司, 来住由樹, 武田俊彦, 髙木 学, 山田了士
Organizer
第116回日本精神神経学会学術総会9月28日（月）～30日
Related Report
-
-
-
-
