Pathogenesis of Sleep-Wake Disorders and Psychiatric Disorders Caused by Autoantibodies

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08037
• 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: University of Tsukuba
• Principal Investigator: Kanbayashi Takashi 筑波大学, 国際統合睡眠医科学研究機構, 教授 (50323150)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: ナルコレプシー / オレキシン / 視神経脊髄炎 / NMDA受容体脳炎

Outline of Final Research Achievements

Narcolepsy (NA) was shown to be caused by loss of orexin neurons in 2000. 90% of patients are positive for HLA-DR*1501 and DQB1*0602, indicating that an immune mechanism is involved, but the mechanism of orexin loss is not clear. To investigate the pathogenesis of idiopathic NA, we have continued to measure orexin levels in patients with hypersomnia, which is considered to be symptomatic. The most frequent cases are neuromyelitis optica (NMO) caused by AQP4 and MOG antibodies. Hypersomnia often improves with treatment of the underlying disease. Less frequently, cases with Ma2 antibodies have also been reported. In the search for the cause of hypersomnia in elderly patients, we found Ma2 antibodies and testicular tumors, but hypersomnia did not improve after removal of the tumors. We assume that BBB vulnerability may be the basis of both diseases. In our study of NMDAR antibodies, the positivity rate was about 0.5% in psychiatric inpatients.

Free Research Field

睡眠覚醒障害

Academic Significance and Societal Importance of the Research Achievements

ナルコレプシー(NA)はオレキシン神経の脱落で発症することが明らかとなり、免疫機序が働いていることは間違いないが、その機序は明らかでは無い。病態を探る目的のため症候性と考えられる過眠症の症例においてもオレキシン値の測定を続けている。頻度が高いのはAQP4抗体とMOG抗体による視神経脊髄炎(NMO)が筆頭である。原疾患の治療により過眠症も改善する場合が多い。Ma2抗体による 症例も存在する。NAの治療中に NMDAR脳炎を発症する症例は散見される。両疾患の共通の基盤にはBBBの脆弱性があるのではと想定してい る。NMDAR抗体の検討では、精神科の入院患者では0.5％程度の陽性率であった。