1997 Fiscal Year Annual Research Report

精神分裂病と感情障害の発症と経過に関与する神経伝達物質関連遺伝子変異の検索

Research Project

Project/Area Number	07457207
Research Institution	Tokyo Medical and Dental University
Principal Investigator	融道男東京医科歯科大学, 医学部, 教授 (20013972)
Co-Investigator(Kenkyū-buntansha)	有波忠雄筑波大学, 基礎医学系, 助教授 (10212648) 渡辺明子東京医科歯科大学, 医学部, 技官 (40210992) 車地暁生東京医科歯科大学, 医学部, 助手 (00251504) 澁谷治男東京医科歯科大学, 医学部, 助教授 (10158959)
Keywords	精神分裂病 / 感情障害 / アルコール依存症 / ドーパミンD2受容体遺伝子変異 / MTHFR遺伝子変異
Research Abstract	精神分裂病419名、感情障害78名、アルコール依存症393名、対照579名のDNAを用いて変異遺伝子との関連研究を行い、下記の所見を得た。 1、精神分裂病 1)ドーパミンD2受容体遺伝子(DRD2)のSer311Cysは分裂病で保有するものが有意に多く、特に陰性症状のない分裂病で17%の患者が保有し、対照(4%)に比し有意に(p<0.00001)高頻度であった。 2)DRD2のプロモーター領域で-141番目のシトシンが挿入(Ins)または欠失(Del)している多型を見出した。分裂病では-141C挿入型対立遺伝子をもつ個体が罹患する可能性が高いことが予想された(OR:0.06、p<0.001)。 3)methylenetetrabydrofolate reductase(MTHFR)遺伝子のAla677Val多型について関連を調べたところ、分裂病にこの多型を有する者が多かった(OR:1.9、p<0.0006)。 2、感情障害 1)DRD2のCys311変異は感情障害全体では7.7%にみられたが、気分と一致しない精神病症状を有する患者に33.3%という高率でこの変異が認められた(p<0.01)。 2)MTHFRの変異遺伝子Val6,77は大うつ病の患者で対照より高頻度に認められた(OR:2.8、p=0.005)。 3、アルコール依存症 1)DRD2のCys311変異は依存症群で有意に高頻度にみられた(p<0.04)。 2)DRD2の-141C Ins/Del多型-141Ins対立遺伝子の頻度が有意に高かった(p<0.0005)。 3)DRD2のTaqIA1対立遺伝子頻度も依存症群で有意に高かった(p<0.006)。以上はすべて症例-対照関連研究において有意な差を見出したものについてだけまとめたが、これら精神疾患にみられる多様な遺伝子変異は、家族集積を示す複雑遺伝疾患に属する精神疾患の解明を示唆する所見の一端であると思われる。

Research Products

(19 results)

All Other

All Publications (19 results)

[Publications] Nankai,M., Yamada,S., Muneoka,K., Toru,M.: "Increased 5-HT2-mediated behavior eleven days after shock in learned helpless rats." European Journal of Pharmacology.281. 123-130. (1995)
[Publications] Yamada,S., Watanabe,A., Nankai,M., Toru,M.: "Acute immobilization stress reduces(±)DOI-induced 5-HT2A recrptor-mediated head shakes in rats." Psychopharmacology.119. 9-14. (1995)
[Publications] Arinami,T., Itokawa,M., Aoki,J., Shibuya,H., Ookubo,Y., Iwawaki,A., Ota,K., Shimizu, H., Hamaguchi,H., Toru,M.: "Further association study on dopamine D2 receptor variant S311C in schizophrenia and affective disorders." American Journal of Medical Genetics.67. 133-8. (1996)
[Publications] Arinami,T., Ling Li, Mitushio,H., Itokawa,M., Hamaguchi,H., Toru,M.: "An Insersion/Deletion polymorphism in the angiotensin converting enzyme gene is associated with both brain substance P contents and affective disorders." Biol.Psychiatry.40. 1122-1127. (1996)
[Publications] Arinami,T., Takekoshi,K., Itokawa,M., Hamaguchi,H., Toru,M.: "Failure to find association of the CA repeat polymorphism in the first intron and the Gly-63/Glu-63 polymorphism of the neurotrophin-3 gene with schizophrenia." Psychiatric Genetics.6. 13-15. (1996)
[Publications] Itokawa,M., Toru,M., Ito,K., Tsuga,H., Kameyama,K., Haga,T., Arinami,T., Hamaguchi,H.: "Sequestration of the short and long isoforms of dopamine D2 receptors expressed in Chinese hamster ovary cells." Molecular Pharmacology. 49. 560-566. (1996)
[Publications] Kaneko,K,. Kurumaji,A., Shibuya,H., Nabeshima,T., Toru,M.: "The effects of single and repeated phencyclidine administration of 125I-iomazenil binding in the rat brain." Neurochem.Int.29. 279-287. (1996)
[Publications] Kurumaji,A., Kaneko,K., Toru,M.: "Effects of chronic treatment with haloperidol on [3H]PK11195 binding in the rat brain and peripheral." Neuropharmacology.35. 1075-1079. (1996)
[Publications] Kurumaji,A., Toru,M.: "Postnatal development of periphernal-type benzochiazepine receptors in rat brain and periphernal tissues." Developmental Brain Research.97. 148-151. (1996)
[Publications] Kurumaji,A., Watanabe,A., Kumashiro,S., Semba,J., Toru,M.: "A postmortem study of glycine and its potential precursors in chronic schizophrenics." Neurochemistry International.29(3). 239-245. (1996)
[Publications] Uchiyama,M., Tanaka,K., Isse,K., Toru,M.: "Efficacy of mianserin on symptoms of delirium in the aged:an open trial study." Prog.Neuro-Psychopharmacol. & Biol.Psychiat.20. 651-656. (1996)
[Publications] Toru,M.: "Pharmacotherapy of schizophrenia." Asian Med J.39. 274-278. (1996)
[Publications] Arinami,T., Gao.M., Hamaguchi,H., Toru,M.: "A functional polymorphism in the promoter region of the dopamine D2 receptor gene is associated with schizophrenia." Human Molecular Genetics.6(4). 577-582. (1997)
[Publications] Ishiguro,H., Arinami,T., Yamada,K., Otuka,Y., Toru,M., Shibuya,H.: "An association study between a transcriptional polymerphsm in the serotonin transporter gene and panic disorder in a Japanese population." Psychiatry and Clinical Neuroscinces.51. 333-335. (1997)
[Publications] Arinami,T., Yamada,N., Yamakawa-Kobayashi,K., Hamaguchi,H., Toru,M.: "Methyleneterahydrofolate Reductase Variant and Schizophrenia/Depression" American Journal of Medical Genetics(Neuropsychiatric Genetics).74. 526-528. (1997)
[Publications] Kurumaji,A., Wakai,T., Toru,M.: "Decreases in perpheral-type benzodiazepine receptors in postmortem brains of chronic schizophrenics." J Neural Transm.104. 1361-1370. (1997)
[Publications] Okubo,Y., Suhara,T., Suzuki,K., Kobayashi,K., Inoue,O., Terasaki,O., Someya,Y., Sassa,T., Sudo,Y., Matsushima,E., Iyo,M., Teteno,Y., Toru,M.: "Decreased prefrontal dopamine D1 receptors in schizophrenia revealed by PET." Nature.385(6617). 634-636. (1997)
[Publications] Ishimaru,M., Toru,M.: "The glutamate hypothesis of schizophrenia:therapeutic implications." CNS Drugs.7(1). 47-67. (1997)
[Publications] 融道男, 道明智徳: "精神分裂病の神経伝達物質" ブレイン・サイエンス. 8. 29-38. (1997)

1997 Fiscal Year Annual Research Report

精神分裂病と感情障害の発症と経過に関与する神経伝達物質関連遺伝子変異の検索

Principal Investigator

融 道男 東京医科歯科大学, 医学部, 教授 (20013972)

Research Products

[Publications] Nankai,M., Yamada,S., Muneoka,K., Toru,M.: "Increased 5-HT2-mediated behavior eleven days after shock in learned helpless rats." European Journal of Pharmacology.281. 123-130. (1995)

[Publications] Yamada,S., Watanabe,A., Nankai,M., Toru,M.: "Acute immobilization stress reduces(±)DOI-induced 5-HT2A recrptor-mediated head shakes in rats." Psychopharmacology.119. 9-14. (1995)

[Publications] Arinami,T., Itokawa,M., Aoki,J., Shibuya,H., Ookubo,Y., Iwawaki,A., Ota,K., Shimizu, H., Hamaguchi,H., Toru,M.: "Further association study on dopamine D2 receptor variant S311C in schizophrenia and affective disorders." American Journal of Medical Genetics.67. 133-8. (1996)

[Publications] Arinami,T., Ling Li, Mitushio,H., Itokawa,M., Hamaguchi,H., Toru,M.: "An Insersion/Deletion polymorphism in the angiotensin converting enzyme gene is associated with both brain substance P contents and affective disorders." Biol.Psychiatry.40. 1122-1127. (1996)

[Publications] Arinami,T., Takekoshi,K., Itokawa,M., Hamaguchi,H., Toru,M.: "Failure to find association of the CA repeat polymorphism in the first intron and the Gly-63/Glu-63 polymorphism of the neurotrophin-3 gene with schizophrenia." Psychiatric Genetics.6. 13-15. (1996)

[Publications] Itokawa,M., Toru,M., Ito,K., Tsuga,H., Kameyama,K., Haga,T., Arinami,T., Hamaguchi,H.: "Sequestration of the short and long isoforms of dopamine D2 receptors expressed in Chinese hamster ovary cells." Molecular Pharmacology. 49. 560-566. (1996)

[Publications] Kaneko,K,. Kurumaji,A., Shibuya,H., Nabeshima,T., Toru,M.: "The effects of single and repeated phencyclidine administration of 125I-iomazenil binding in the rat brain." Neurochem.Int.29. 279-287. (1996)

[Publications] Kurumaji,A., Kaneko,K., Toru,M.: "Effects of chronic treatment with haloperidol on [3H]PK11195 binding in the rat brain and peripheral." Neuropharmacology.35. 1075-1079. (1996)

[Publications] Kurumaji,A., Toru,M.: "Postnatal development of periphernal-type benzochiazepine receptors in rat brain and periphernal tissues." Developmental Brain Research.97. 148-151. (1996)

[Publications] Kurumaji,A., Watanabe,A., Kumashiro,S., Semba,J., Toru,M.: "A postmortem study of glycine and its potential precursors in chronic schizophrenics." Neurochemistry International.29(3). 239-245. (1996)

[Publications] Uchiyama,M., Tanaka,K., Isse,K., Toru,M.: "Efficacy of mianserin on symptoms of delirium in the aged:an open trial study." Prog.Neuro-Psychopharmacol. & Biol.Psychiat.20. 651-656. (1996)

[Publications] Toru,M.: "Pharmacotherapy of schizophrenia." Asian Med J.39. 274-278. (1996)

[Publications] Arinami,T., Gao.M., Hamaguchi,H., Toru,M.: "A functional polymorphism in the promoter region of the dopamine D2 receptor gene is associated with schizophrenia." Human Molecular Genetics.6(4). 577-582. (1997)

[Publications] Ishiguro,H., Arinami,T., Yamada,K., Otuka,Y., Toru,M., Shibuya,H.: "An association study between a transcriptional polymerphsm in the serotonin transporter gene and panic disorder in a Japanese population." Psychiatry and Clinical Neuroscinces.51. 333-335. (1997)

[Publications] Arinami,T., Yamada,N., Yamakawa-Kobayashi,K., Hamaguchi,H., Toru,M.: "Methyleneterahydrofolate Reductase Variant and Schizophrenia/Depression" American Journal of Medical Genetics(Neuropsychiatric Genetics).74. 526-528. (1997)

[Publications] Kurumaji,A., Wakai,T., Toru,M.: "Decreases in perpheral-type benzodiazepine receptors in postmortem brains of chronic schizophrenics." J Neural Transm.104. 1361-1370. (1997)

[Publications] Okubo,Y., Suhara,T., Suzuki,K., Kobayashi,K., Inoue,O., Terasaki,O., Someya,Y., Sassa,T., Sudo,Y., Matsushima,E., Iyo,M., Teteno,Y., Toru,M.: "Decreased prefrontal dopamine D1 receptors in schizophrenia revealed by PET." Nature.385(6617). 634-636. (1997)

[Publications] Ishimaru,M., Toru,M.: "The glutamate hypothesis of schizophrenia:therapeutic implications." CNS Drugs.7(1). 47-67. (1997)

[Publications] 融道男, 道明智徳: "精神分裂病の神経伝達物質" ブレイン・サイエンス. 8. 29-38. (1997)

融道男東京医科歯科大学, 医学部, 教授 (20013972)