Biological mechanism of psychiatric symptoms associated with Anti-N-methyl-D-aspartate Receptor Encephalitis.

• Project/Area Number: 15K19740
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Psychiatric science
• Research Institution: Yokohama City University
• Principal Investigator: Suda Akira 横浜市立大学, 医学部, 助教 (60644656)
• Research Collaborator: HIAYASU Yoshio ; KATSUSE Omi ; KISHIDA Ikuko ; SAITO Tomoyuki ; MIYAUCHI Masatoshi ; HATTORI Saki ; ABE Kie
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
• Keywords: 器質性精神障害 / NMDA受容体抗体陽性脳炎 / 自己免疫性脳炎 / 自己免疫疾患 / NMDA受容体脳炎 / 脳器質性精神疾患 / 難治性精神疾患 / 抗NMDA受容体抗体 / 橋本脳症 / 中枢神経ループス / SNPs / SNPｓ / NMDA受容体抗体 / 髄液 / GWAS

Outline of Final Research Achievements

We tried to elucidate the biomarkers that affect the severity and differences in the mental symptoms of patients with anti-N-methyl-d-asparatic acid (NMDA) receptor encephalitis. As a result,significant association was found between serum antibody titer and cognitive function in NMDA receptor antibody positive patients. In addition, cerebrospinal fluid antibody titer and cognitive function are associated in general psychiatric patients. Although we could not find a genetic marker for differentiating general mental disease patients and NMDA receptor antibody encephalitis patients, we will ccontinue to cllect samples and performe a comprehensive genetic reserch with a larger number of subjects.

Academic Significance and Societal Importance of the Research Achievements

抗NMDA受容体抗体陽性脳炎患者でしばしば精神症状が生じる原因に、NMDA受容体抗体が関与している可能性が示された。難治性の精神疾患と考えられていた患者の一部は抗NMDA受容体抗体陽性脳炎患者が含まれる可能性があることから、そのような患者には免疫学的な治療が有効である可能性が示唆されるとともに、今後、NMDA受容体抗体患者をモデルとした研究を進めることは、精神疾患の症状発現メカニズムを解明する端緒となりうると考えられた。

Research Products

• [Journal Article] Effects of long-acting injectable antipsychotics versus oral antipsychotics on autonomic nervous system activity in schizophrenic patients (2018)
  • Author(s): Suda Akira、Hattori Saki、Kishida Ikuko、Miyauchi Masatoshi、Shiraishi Yohko、Fujibayashi Mami、Tsujita Natsuki、Ishii Chie、Ishii Norio、Moritani Toshio、Hirayasu Yoshio
  • Journal Title: Neuropsychiatric Disease and Treatment Volume: Volume 14 Pages: 2361-2366
  • DOI: 10.2147/ndt.s173617
  • Peer Reviewed / Open Access
• [Journal Article] Association between dysfunction of autonomic nervous system activity and mortality in schizophrenia (2018)
  • Author(s): Hattori Saki、Suda Akira、Kishida Ikuko、Miyauchi Masatoshi、Shiraishi Yohko、Fujibayashi Mami、Tsujita Natsuki、Ishii Chie、Ishii Norio、Moritani Toshio、Saigusa Yusuke、Hirayasu Yoshio
  • Journal Title: Comprehensive Psychiatry Volume: 86 Pages: 119-122
  • DOI: 10.1016/j.comppsych.2018.08.002
  • Peer Reviewed
• [Journal Article] Effects of ABCB1 gene polymorphisms on autonomic nervous system activity during atypical antipsychotic treatment in schizophrenia (2018)
  • Author(s): Hattori Saki、Suda Akira、Kishida Ikuko、Miyauchi Masatoshi、Shiraishi Yohko、Fujibayashi Mami、Tsujita Natsuki、Ishii Chie、Ishii Norio、Moritani Toshio、Taguri Masataka、Hirayasu Yoshio
  • Journal Title: BMC Psychiatry Volume: 18 Issue: 1 Pages: 231-231
  • DOI: 10.1186/s12888-018-1817-5
  • Peer Reviewed
• [Journal Article] Effects of four atypical antipsychotics on autonomic nervous system activity in schizophrenia (2018)
  • Author(s): Hattori Saki、Kishida Ikuko、Suda Akira、Miyauchi Masatoshi、Shiraishi Yohko、Fujibayashi Mami、Tsujita Natsuki、Ishii Chie、Ishii Norio、Moritani Toshio、Taguri Masataka、Hirayasu Yoshio
  • Journal Title: Schizophrenia Research Volume: 193 Pages: 134-138
  • DOI: 10.1016/j.schres.2017.07.004
  • NAID: 130007901367
  • Peer Reviewed / Open Access
• [Journal Article] Associations of ABCB1 gene polymorphisms with aripiprazole-induced autonomic nervous system dysfunction in schizophrenia (2017)
  • Author(s): Hattori Saki、Suda Akira、Kishida Ikuko、Miyauchi Masatoshi、Shiraishi Yohko、Fujibayashi Mami、Tsujita Natsuki、Ishii Chie、Ishii Norio、Moritani Toshio、Taguri Masataka、Hirayasu Yoshio
  • Journal Title: Schizophrenia Research Volume: － Pages: 16-18
  • DOI: 10.1016/j.schres.2017.11.020
  • Peer Reviewed / Open Access
• [Journal Article] Regional cerebral glucose metabolism in systemic lupus erythematosus patients with major depressive disorder (2017)
  • Author(s): Saito Tomoyuki、Tamura Maasa、Chiba Yuhei、Katsuse Omi、Suda Akira、Kamada Ayuko、Ikura Takahiro、Abe Kie、Ogawa Matsuyoshi、Minegishi Kaoru、Yoshimi Ryusuke、Kirino Yohei、Ihata Atsushi、Hirayasu Yoshio
  • Journal Title: Journal of the Neurological Sciences Volume: 379 Pages: 127-130
  • DOI: 10.1016/j.jns.2017.05.059
  • Peer Reviewed
• [Presentation] 免疫療法が奏功した”treatable" DLBの1例 (2019)
  • Author(s): 阿部 紀絵、千葉 悠平、戸代原 奈央、許 博陽、吉見 明香、須田 顕
  • Organizer: 115回日本精神神経学会学術総会
• [Presentation] Investigation of Cognitive Functions Associated with Autoantibodies Against NMDA Glutamate Receptor in Psychiatric Patients with and without Anti-Thyroid Antibodies. (2018)
  • Author(s): Kie Abe, Yuhei Chiba, Omi Katsuse, Takahiro Ikura, Tomoyuki Saito, Ayuko Kamada, Akira Suda, Saki Hattori, Yukitoshi Takahashi and Yoshio Hirayasu
  • Organizer: WPA thematic congress.
  • Int'l Joint Research
• [Presentation] 「自己免疫と精神疾患」にて，「橋本脳症とNeuropsychiatric SLEにおける，精神免疫学的側面について」 (2017)
  • Author(s): 千葉悠平，勝瀬大海，伊倉崇浩，斎藤知之，阿部紀絵，鎌田鮎子，服部早紀，須田顕，高橋幸利，平安良雄
  • Organizer: 第113回日本精神神経学会学術総会
• [Presentation] うつ病を伴う全身性エリテマトーデス患者の局所脳糖代謝(Regional Cerebral Glucose Metabolism in Systemic Lupus Erythematosus Patients with Major Depressive Disorder)． (2017)
  • Author(s): 29.斎藤 知之, 田村 真麻, 千葉 悠平, 勝瀬 大海, 須田 顕, 鎌田 鮎子, 伊倉 崇浩, 服部 早紀, 阿部 紀絵, 尾川 松義, 峯岸 薫, 吉見 竜介, 井畑 淳, 平安 良雄
  • Organizer: 第39回日本生物学的精神医学会・第47回日本神経精神薬理学会合同年会