The influence of autoimmune antibodies on psychiatric diseases

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10188
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Okayama University
• Principal Investigator: Takaki Manabu 岡山大学, 大学病院, 講師 (60452570)
• Research Collaborator: Sakamoto Shinji ; Kawai Hiroki
• Project Period (FY): 2016-04-01 – 2019-03-31
• 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

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.

Free Research Field

精神神経科学

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。