Examination of the Findings Suggesting Niemann–Pick Disease Type C in Patients with Schizophrenia

• Project/Area Number: 17K10282
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Shiga University of Medical Science (2019); Dokkyo Medical University (2017-2018)
• Principal Investigator: Fujii Kumiko 滋賀医科大学, 医学部, 准教授 (70314151)
• Co-Investigator(Kenkyū-buntansha): 尾關 祐二 滋賀医科大学, 医学部, 教授 (90303768)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
• Keywords: 統合失調症 / ニーマンピック病C型 / 精神医学

Outline of Final Research Achievements

We measured the bile acid content in urine using liquid chromatography/mass spectrometry and serum oxysterol using quadrupole time-of-flight liquid chromatography/mass spectrometry in the patients with neurological symptoms. We analyzed NPC1 and NPC2 genes using Ion PGM in the patients with schizophrenia also without neurological symptoms. mRNA expression levels of NPC1 and NPC2 were measured and analyzed in patients with schizophrenia and healthy controls using TaqMan method and semi-quantitative assessment with beta-actin was performed.
One patient had significantly high biological marker levels for NPC. In patients with schizophrenia, we found a new single nucleotide polymorphism (SNP) that induces amino acid substitution. mRNA expression levels of NPC1 and NPC2 in patients with schizophrenia were significantly higher than those in normal controls.Further investigations are required to reveal the significance of the new SNP and the differences in mRNA expression levels.

Academic Significance and Societal Importance of the Research Achievements

統合失調症患者の治療中にジストニアなどの不随意運動が出現した際には、抗精神病薬の副作用と判断することが多く、ニーマンピック病Ｃ型（NPC）を念頭において鑑別を行うことは少ないのが現状である。しかし、我々は統合失調症と診断されている症例の中に、細胞内にコレステロールが沈着している症例やNPCのバイオマーカーといわれる物質が異常値を示す症例、遺伝子変異を伴う症例がいること、ｍRNA の発現量が有意に統合失調症で高値であることも明らかとなった。それらの意味合いを明らかにするには更なる研究が必要であるが、統合失調症と診断されている症例の中にNPCの可能性を踏まえた視点での診療が重要であると考えられた。

Research Products

• [Journal Article] Slower Titration of Lamotrigine Reduces the Risk of Rash. (2020)
  • Author(s): Kumiko Fujii, Hiroaki Okayasu, Takahiro Shinozaki, Kazutaka Shimoda, Yuji Ozeki
  • Journal Title: Psychiatry and clinical neurosciences Volume: 74 Issue: 4 Pages: 282-283
  • DOI: 10.1111/pcn.12987
  • Peer Reviewed
• [Journal Article] Examination of the findings suggesting Niemann-Pick disease type C in patients with schizophrenia (2019)
  • Author(s): Fujii K, Maekawa M, Ozeki Y, Eto Y, Saito T, Shinozaki M, Arime Y, Nagashima T, Okayasu H, Ishii S, Shimoda K
  • Journal Title: Schizophrenia Bulletin Volume: 45 Issue: Supplement_2 Pages: S260-S261
  • DOI: 10.1093/schbul/sbz018.429
  • Peer Reviewed / Open Access
• [Journal Article] Structural Determination of Lysosphingomyelin-509 and Discovery of Novel Class Lipids from Patients with Niemann-Pick Disease Type C (2019)
  • Author(s): Masamitsu Maekawa, Isamu Jinnoh, Yotaro Matsumoto, Aya Narita, Ryuichi Mashima, Hidenori Takahashi, Anna Iwahori, Daisuke Saigusa, Kumiko Fujii, Ai Abe, Katsumi Higaki, Shosei Yamauchi, Yuji Ozeki, Peter T Clayton, Hiroaki Yamaguchi, Nariyasu Mano, et al.
  • Journal Title: International Journal of Molecular Sciences Volume: 20 Issue: 20 Pages: 5018-5018
  • DOI: 10.3390/ijms20205018
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Association of Genetic Variants at 22q11.2 Chromosomal Region with Cognitive Performance in Japanese Patients with Schizophrenia. (2019)
  • Author(s): Akiyama K, Saito A, Saito S, Ozeki Y, Watanabe T, Fujii K, Shimoda K
  • Journal Title: Schizophrenia Research: Cognition Volume: 印刷中 Pages: 100134-100134
  • DOI: 10.1016/j.scog.2019.100134
  • Peer Reviewed / Open Access
• [Journal Article] Investigation of the Proarrhythmic Effects of Antidepressants according to QT Interval, QT Dispersion and T Wave Peak-to-End Interval in the Clinical Setting (2019)
  • Author(s): Hiroaki Okayasu, Yuji Ozeki, Kumiko Fujii, Yumiko Takano, Takahiro Shinozaki, Masami Ohrui, and Kazutaka Shimoda
  • Journal Title: Psychiatry Investigation Volume: 16(2): Issue: 2 Pages: 159-166
  • DOI: 10.30773/pi.2018.12.11
  • Peer Reviewed / Open Access
• [Presentation] Examination of the findings suggesting Niemann-Pick disease type C in patients with schizophrenia (2019)
  • Author(s): Fujii K, Maekawa M, Ozeki Y, Eto Y, Saito T, Shinozaki M, Arime Y, Nagashima T, Okayasu H, Ishii S, Shimoda K
  • Organizer: The 2019 congress of the schizophrenia international society
  • Int'l Joint Research
• [Presentation] Are “ALL” of neurological symptoms with schizophrenia induced by antipsychotics? ~Possibility of Niemann-Pick disease type C~ (2019)
  • Author(s): Fujii K, Maekawa M, Ozeki Y, Eto Y, Saito T, Shinozaki M, Arime Y, Nagashima T, Okayasu H, Shimoda K
  • Organizer: 6th Asian College of Neuropsychopharmacology
  • Int'l Joint Research
• [Presentation] 統合失調症と診断された症例を対象とした成人型ニーマンピック病C型を示唆する所見の検討 (2019)
  • Author(s): 藤井久彌子, 前川正充, 尾関祐二, 衞藤義勝, 齋藤尚大, 篠﨑將貴, 有銘預世布, 永島隆秀, 岡安寛明, 石井沙安也, 下田和孝
  • Organizer: 第115回日本精神神経学会
• [Presentation] 『薬剤性』と通常判断する統合失調症のジストニアを再検討する ―成人型ニーマンピック病C型の可能性― (2019)
  • Author(s): 藤井久彌子, 前川正充, 尾関祐二, 衞藤義勝, 齋藤尚大, 篠﨑將貴, 有銘預世布, 永島隆秀, 岡安寛明, 下田和孝
  • Organizer: 第40回日本臨床薬理学会
• [Presentation] 抗精神病薬治療中の神経症状はすべて薬剤性か ―成人型ニーマンピック病C型の可能性を検討する― (2019)
  • Author(s): 藤井久彌子, 前川正充, 尾関祐二, 衞藤義勝, 齋藤尚大, 篠﨑將貴, 有銘預世布, 永島隆秀, 岡安寛明, 石井沙安也, 下田和孝
  • Organizer: 第41回日本生物学的精神医学会
• [Presentation] 統合失調症がジストニアを呈した場合、必ず薬剤性なのか－顕著なジストニアや小脳失調を呈する症例の検討－ (2018)
  • Author(s): 藤井 久彌子、前川 正充、衞藤 義勝、尾関 祐二、齋藤 尚大、有銘 預世布、永島 隆秀、岡安 寛明、篠崎 隆央、竹内 祥貴、秋山 一文、下田 和孝
  • Organizer: 第13回日本統合失調症学会
• [Presentation] Review of the findings which suggest Niemann-Pick disease type C in the patients with schizophrenia (2018)
  • Author(s): Kumiko Fujii, Masamitsu Maekawa, Yuji Ozeki, Yoshikatsu Eto, Takahiro Saito, Yosefu Arime, Hiroaki Okayasu, Takahiro Shinozaki, Kazufumi Akiyama, Kazutaka Shimoda
  • Organizer: 第40回日本生物学的精神医学会
• [Presentation] 統合失調症がジストニアを呈した場合、必ず薬剤性なのか。 (2018)
  • Author(s): 藤井久彌子、前川正充、衞藤義勝、尾関祐二、齋藤尚大、有銘預世布、永島隆秀、 岡安寛明、篠﨑隆央、竹内祥貴、秋山一文、下田和孝
  • Organizer: 第13回日本統合失調症学会