Dimensional approach to mental disease through autoantibodies

2021 Fiscal Year Final Research Report

• 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: Takaki Manabu 岡山大学, 大学病院, 講師 (60452570)
• Project Period (FY): 2019-04-01 – 2022-03-31
• 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

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.

Free Research Field

精神医学

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。