Project/Area Number |
09671008
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Psychiatric science
|
Research Institution | TEIKYO UNIVERSITY |
Principal Investigator |
KUNUGI Hiroshi Teikyo University School of Medicine, Lecturer, 医学部, 講師 (40234471)
|
Co-Investigator(Kenkyū-buntansha) |
LEE Kyu-Bak Teikyo University School of Medicine, Assistant, 医学部, 助手 (40307202)
NANKO Shinichiro Teikyo University School of Medicine, Professor, 医学部, 教授 (60101127)
|
Project Period (FY) |
1997 – 1998
|
Project Status |
Completed (Fiscal Year 1998)
|
Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1997: ¥2,100,000 (Direct Cost: ¥2,100,000)
|
Keywords | Schizophrenia / Neurotrophic factor / Molecular genetics / Hippocampus / Neurodevelopment / Neurotrophin-3 / Brain derived neurotrophic factor / ニューロトロフィン-3 / 関連研究 |
Research Abstract |
Polymorphisms of gens encoding neurotrophic factors are possibly involved in the pathogenesis of schizophrenia. We searched for polymorphisms in the neurotrophin-3 (NT-3), brain derived neurotrophic factor (BDNF), and glial cell-line derived neurotrophic factor (GDNF) genes and explored their effects on susceptibility and neurodevelopmental abnormalities in schizophrenia. The Gly(-63)Glu polymorphism of the NT-3 gene was not significantly associated with susceptibility to schizophrenia when severity of the disease was not taken into account. A nucleotide substitution was found in the vicinity of the AP-1 binding site of the NT-3 gene ; however, it was not associated with susceptibility to schizophrenia. A dinucleotide repeat polymorphism of the NT-3 gene, which was previously reported to be associated with the risk of schizophrenia, was found to be associated with reduced volume of hippocampi in schizophrenic subjects, suggesting that this polymorphism may exert an effect on the development of schizophrenia through neurodevelopmental abnormalities of the CNS including hippocampus. We found two nucleotide substitutions in the promoter and 5 untranslated regions of the BDNF gene. These polymorphisms were suggested to be associated with the risk of developing schizophrenia. We could not find any polymorphism for the GDNF gene. Based on information from the Maternal and Child Health Handbook, we confirmed the prenatal underdevelopment in schizophrenia, including development of the eNS.However, there was no significant association of Gly(-63)Glu or the dinucleotide repeat polymorphism of the NT-3 gene with head circumference at birth of schizophrenics.
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