Molecular genetics study of schizophrenia based on neurodevelopmental hypothesis

• Project/Area Number: 07407028
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Teikyo University
• Principal Investigator: NANKO Shinichiro Teikyo Univ., Dept.of Psychiatry.Professor, 医学部, 教授 (60101127)
• Co-Investigator(Kenkyū-buntansha): KUNUGI Hiroshi Teikyo Univ., Dept.of Psychiatry.Professor, 医学部, 講師 (40234471) ; HIROSE Tetsuya Teikyo Univ., Dept.of Psychiatry.Professor, 医学部, 教授 (10101742)
• Project Period (FY): 1995 – 1997
• Project Status: Completed (Fiscal Year 1997)
• Budget Amount: ¥12,900,000 (Direct Cost: ¥12,900,000); Fiscal Year 1997: ¥1,800,000 (Direct Cost: ¥1,800,000); Fiscal Year 1996: ¥2,500,000 (Direct Cost: ¥2,500,000); Fiscal Year 1995: ¥8,600,000 (Direct Cost: ¥8,600,000)
• Keywords: schizophrenia / neurodevelopmental / ciliary neurotrophic factor (CNTF) / mutation / polymorphism / brain-derived neurotrophic factor (BDNF) / neurotrophin-3 (Nt-3) / 神経発達障害 / CNTF / 変異

Research Abstract

Neurotrophic factors are believed to play an essential role in the neurodevelopment such as in the cellular proliferation, migration, differentiation and death or survival of neurons in central nervous system. Recently, a significant difference was found in the distribution of the CA repeat polymorphism of the neurotrophin-3 (NT-3) gene. (Nanko et al.1994). Thome et al. (Nature Genetics 13 : 144,1996) also reported a significant increase of a null mutation of the ciliary neurotrophic factor (CNTF) gene in mental disorders.
We have been systematically conducting studies to examine possible roles of neurotrophic factors in the etiology of schizophrenia. The results were as follows
1) Neurotrophin-3 : Significant difference of the DNA variants of NT-3 gene and schizophrenia was found, when parients were restricted to severe case (Hattori and Nanko, BBRC 209 : 213-218,1995). we also found A to C mutation in the promoter region of neurotrophin-3 at the position of-1232. The frequency of A allele was 88% among general population. No association was found between this mutation and schizophrenia (Hattori et al.Unpublished).
2) Brain derived neurotrophic factor (BDNF) : We investigated a dinucleotide polymorphic site of the BDNF gene according to Proeschel et al.1992). The PCR fragment of Japanese subjects was longer than in Caucasian subjects reported by Proeschel et al. (1992). No association was found between this polymorphism and schizophrenia.
3) Ciliary neurotrophic factors (CNTF) : We investigated a null mutation of CNTF gene reported by Takahashi et al. (1994) in 138 Japanese patients with schizophrenia and 140 healthy controls. No significant difference was observed between patients and controls.

Research Products

• [Publications] Hattori, M.and Nanko, S.: "Association of neurotrophin-3 gene variant with severe forms of schizophrenia." Biochem Biophys Res Comm. 209. 513-518 (1995)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Sasaki, T.et al.: "Brain-derived neurotrophic factor gene and schizophrenia in Japanese subjects." American Journal of Medical Genetics. 74. 443-444 (1997)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Sakai, T.et al.: "Schizophrenia and the ciliary neurotrophic factor(CNTF)gene: no evidence for the association." Psychiatry Research. 71. 7-10 (1997)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Hattori, M.and Nanko, S.: "Association of neurotrophin-3 gene variant with severe forms of schizophrenia." BBRC. 209. 513-518 (1995)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Sasaki, T., Dai, X-Y,Kuwata, S,Fukuda, R,Kunugi, H., Hattori, M and Nanko, S.: "Brain-derived neurotrophic factor gene and schizophrenia in Japanese subjects." Am J Med Genet. 74. 443-444 (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Sakai, T., Sasaki, T., Tatsumi, M., Kunugi, H., Hattori, M.and Nanko, S.: "Schizophrenia and the ciliary neurotrophic factor (CNTF) gene : no evidence for the association." Psychiatry Res. 71. 7-10 (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Hattori,M.and Nanko,S.: "Association of neurotrophin-3 gene variant with severe forms of schizophrenia." Biochem Biophys Res Comm. 209. 513-518 (1995)
• [Publications] Sasaki,T.et al.: "Brain-derived neurotrophic factor gene and schizophrenia in Japanese subjects." American Journal of Medical Genetics. 74. 443-444 (1997)
• [Publications] Sakai,T.et al.: "Schizophrenia and the ciliary neurotrophic factor(CNTF)gene:no evidence for the association." Psychiatry Research. 71. 7-10 (1997)
• [Publications] Sasaki et al.: "The brain nervotvophic factor gene and schijophveina in Japanese subjects." Am J.Med Geuet. (in press).