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尾崎 紀夫 Norio Ozaki 名古屋大学大学院医学系研究科精神医学・教授・医学博士


専門分野

精神医学(ゲノム医学アプローチによる精神障害の分子病態解明)

略歴

1982年 3月
名古屋大学医学部卒業
1990年 5月
名古屋大学より医学博士号
1990年 7月
National Institute of Mental Health, Visiting Fellow
1995年 9月
藤田保健衛生大学医学部講師
1998年 5月
藤田保健衛生大学医学部教授
2003年10月
名古屋大学大学院医学系研究科教授

研究課題名

精神障害の病態解明

これまでの成果と今後の展望

A. 研究目的 
我々は日本人統合失調症の全ゲノム関連解析(GWAS)を実施した。その結果に基づき、上位の関連シグナルを独立サンプルでフォローアップしたが、single-locus analysisではゲノムワイドに有意な関連は確認できなかった。一方、既報のGWASの結果に一致して、NOTCH4の関連を支持する所見を得た(rs2071287: pmeta=5.1×10-5)。
本年度は上述のGWASの結果と生物学的知見に基づき、候補遺伝子としてVAV3PTPRAを選択し、本疾患の病態への関与を検討した。VAV3領域は日本人統合失調症を対象にしたGWASと連鎖解析の両方で関連が示唆され、機能的には軸索ガイダンスへの関与が報告されている。PTPRA領域もGWASと連鎖解析で本疾患との関連が示唆され、チロシンリン酸化を介したシグナル伝達系の異常と統合失調症の関連が指摘されていた。本研究では、VAV3についてはvoxel-based morphometry (VBM)解析とリシーケンス解析を行ない、PTPRAについてはPtpra-/-マウスの行動解析と中枢神経系での遺伝子発現解析、患者死後脳でのPTPRA発現解析を実施した。この2つの候補遺伝子の解析から統合失調症の分子病態を解明することが本研究の目的である。

B. 研究成果 
VAV3のVBM解析では日本人GWASで関連シグナルを見出したrs1410403が左上側頭回と左中側頭回の体積に関連することが示された(Figure1)。この領域の体積減少は統合失調症に特徴的な所見として知られる。リシーケンス解析は新規の稀なミスセンス変異を4つ同定した。独立サンプルで関連解析を実施し、その中の1つの変異(Glu741Gly)が統合失調症と関連した(P = .02)(Figure2)。Glu741Glyは発症に対してprotectiveに作用し、in silico解析はVAV3の機能に対する機能的影響を予測した。この結果は「効果の大きな稀な変異」も「効果の小さなありふれた変異」も発症脆弱性に関与することを示している。従って、リシーケンス解析やcopy number variantの解析とGWASは統合失調症の遺伝学的解析において互いに相補的な手法といえる。
PTPRAの解析では、Ptpra-/-マウスが統合失調症のエンドフェノタイプといえるメタンフェタミン誘発性過活動、感覚運動ゲート機構の異常、驚愕反応への馴化欠如を示した。またPtpra-/-マウスは死後脳研究で報告されたミエリン遺伝子の発現低下を示した。PTPRAは遺伝学的に統合失調症と関連し(Figure3)、患者死後脳の解析から背外側前頭前野でPTPRA mRNAの発現低下を認めた。以上の結果はPTPRAが統合失調症の発症脆弱性に関与することが示され、本疾患で認められる白質異常と神経伝達系機能障害の因果関係の解明が今後進むと期待される。

主要研究業績

  1. Furumura K, Koide T, Okada T, Murase S, Aleksic B, Hayakawa N, Shiino T, Nakamura Y, Tamaji A, Ishikawa N, Ohoka H, Usui H, Banno N, Morita T, Goto S, Kanai A, Masuda T, Ozaki N: Prospective Study on the Association between Harm Avoidance and Postpartum Depressive State in a Maternal Cohort of Japanese Women. PLoS One, in press (2012)
  2. Aleksic B, Kushima I, Hashimoto R, Ohi K, Ikeda M, Yoshimi A, Nakamura Y, Ito Y, Okochi T, Fukuo Y, Yasuda Y, Fukumoto M, Yamamori H, Ujike H, Suzuki M, Inada T, Takeda M, Kaibuchi K, Iwata N, Ozaki N: Analysis of the VAV3 as Candidate Gene for Schizophrenia: Evidences From Voxel-Based Morphometry and Mutation Screening. Schizophr Bull, in press (2012)
  3. Tamaji A, Iwamoto K, Kawamura Y, Takahashi M, Ebe K, Kawano N, Kunimoto S, Aleksic B, Noda Y, Ozaki N: Differential effects of diazepam, tandospirone, and paroxetine on plasma brain-derived neurotrophic factor level under mental stress. Hum Psychopharmacol, in press (2012)
  4. Kushima I, Okada T, Ozaki N: Developmental disorders. Brain Nerve, 64, 139-147 (2012)
  5. Torii Y, Iritani S, Sekiguchi H, Habuchi C, Hagikura M, Arai T, Ikeda K, Akiyama H, Ozaki N: Effects of aging on the morphologies of Heschl's gyrus and the superior temporal gyrus in schizophrenia: a postmortem study. Schizophr Res, 134, 137-142 (2012)
  6. Banno M, Koide T, Aleksic B, Yamada K, Kikuchi T, Kohmura K, Adachi Y, Kawano N, Kushima I, Ikeda M, Inada T, Yoshikawa T, Iwata N, Ozaki N: A case control association study and cognitive function analysis of neuropilin and tolloid-like 1 gene and schizophrenia in the Japanese population. PLoS One, 6, e28929 (2011)
  7. Fuchikami M, Morinobu S, Segawa M, Okamoto Y, Yamawaki S, Ozaki N, Inoue T, Kusumi I, Koyama T, Tsuchiyama K, Terao T: DNA methylation profiles of the brain-derived neurotrophic factor (BDNF) gene as a potent diagnostic biomarker in major depression. PLoS One, 6, e23881 (2011)
  8. Ikeda M, Aleksic B, Kinoshita Y, Okochi T, Kawashima K, Kushima I, Ito Y, Nakamura Y, Kishi T, Okumura T, Fukuo Y, Williams HJ, Hamshere ML, Ivanov D, Inada T, Suzuki M, Hashimoto R, Ujike H, Takeda M, Craddock N, Kaibuchi K, Owen MJ, Ozaki N, O'Donovan MC, Iwata N: Genome-wide association study of schizophrenia in a Japanese population. Biol Psychiatry, 69, 472-478 (2011)
  9. Ishikawa N, Goto S, Murase S, Kanai A, Masuda T, Aleksic B, Usui H, Ozaki N: Prospective study of maternal depressive symptomatology among Japanese women. J Psychosom Res, 71, 264-269 (2011)
  10. Kishi T, Yoshimura R, Fukuo Y, Kitajima T, Okochi T, Matsunaga S, Inada T, Kunugi H, Kato T, Yoshikawa T, Ujike H, Umene-Nakano W, Nakamura J, Ozaki N, Serretti A, Correll CU, Iwata N: The CLOCK gene and mood disorders: a case-control study and meta-analysis. Chronobiol Int, 28, 825-833 (2011)
  11. Niwa M, Matsumoto Y, Mouri A, Ozaki N, Nabeshima T: Vulnerability in early life to changes in the rearing environment plays a crucial role in the aetiopathology of psychiatric disorders. Int J Neuropsychopharmacol, 14, 459-477 (2011)
  12. Sekiguchi H, Iritani S, Habuchi C, Torii Y, Kuroda K, Kaibuchi K, Ozaki N: Impairment of the tyrosine hydroxylase neuronal network in the orbitofrontal cortex of a genetically modified mouse model of schizophrenia. Brain Res, 1392, 47-53 (2011)
  13. Takahashi N, Nielsen KS, Aleksic B, Petersen S, Ikeda M, Kushima I, Vacaresse N, Ujike H, Iwata N, Dubreuil V, Mirza N, Sakurai T, Ozaki N, Buxbaum JD, Sap J: Loss of function studies in mice and genetic association link receptor protein tyrosine phosphatase alpha to schizophrenia. Biol Psychiatry, 70, 626-635 (2011)
  14. Takata A, Kim SH, Ozaki N, Iwata N, Kunugi H, Inada T, Ujike H, Nakamura K, Mori N, Ahn YM, Joo EJ, Song JY, Kanba S, Yoshikawa T, Kim YS, Kato T: Association of ANK3 with bipolar disorder confirmed in East Asia. Am J Med Genet B Neuropsychiatr Genet, 156B, 312-315 (2011)
  15. Yoshimura T, Usui H, Takahashi N, Yoshimi A, Saito S, Aleksic B, Ujike H, Inada T, Yamada M, Uchimura N, Iwata N, Sora I, Iyo M, Ozaki N: Association analysis of the GDNF gene with methamphetamine use disorder in a Japanese population. Prog Neuropsychopharmacol Biol Psychiatry, 35, 1268-1272 (2011)
  16. Kushima I, Nakamura Y, Aleksic B, Ikeda M, Ito Y, Shiino T, Okochi T, Fukuo Y, Ujike H, Suzuki M, Inada T, Hashimoto R, Takeda M, Kaibuchi K, Iwata N, Ozaki N: Resequencing and Association Analysis of the KALRN and EPHB1 Genes And Their Contribution to Schizophrenia Susceptibility. Schizophr Bull, in press (2011)
  17. Ikeda M, Aleksic B, Kinoshita Y, Okochi T, Kawashima K, Kushima I, Ito Y, Nakamura Y, Kishi T, Okumura T, Fukuo Y, Williams HJ, Hamshere ML, Ivanov D, Inada T, Suzuki M, Hashimoto R, Ujike H, Takeda M, Craddock N, Kaibuchi K, Owen MJ, Ozaki N, O'Donovan MC, Iwata N: Genome-Wide Association Study of Schizophrenia in a Japanese Population. Biol Psychiatry, 69, 472-478 (2011)
  18. Syu A, Ishiguro H, Inada T, Horiuchi Y, Tanaka S, Ishikawa M, Arai M, Itokawa M, Niizato K, Iritani S, Ozaki N, Takahashi M, Kakita A, Takahashi H, Nawa H, Keino-Masu K, Arikawa-Hirasawa E, Arinami T: Association of the HSPG2 Gene with Neuroleptic-Induced Tardive Dyskinesia. Neuropsychopharmacology, 35, 1155-1164 (2010)
  19. Hashimoto R, Noguchi H, Hori H, Nakabayashi T, Suzuki T, Iwata N, Ozaki N, Kosuga A, Tatsumi M, Kamijima K, Harada S, Takeda M, Saitoh O, Kunugi H: A genetic variation in the dysbindin gene (DTNBP1) is associated with memory performance in healthy controls. World J Biol Psychiatry, 11, 431-438 (2010)
  20. Ishiguro H, Koga M, Horiuchi Y, Noguchi E, Morikawa M, Suzuki Y, Arai M, Niizato K, Iritani S, Itokawa M, Inada T, Iwata N, Ozaki N, Ujike H, Kunugi H, Sasaki T, Takahashi M, Watanabe Y, Someya T, Kakita A, Takahashi H, Nawa H, Arinami T: Supportive evidence for reduced expression of GNB1L in schizophrenia, Schizophr Bull, in press (2011)
  21. Takahashi M, Hayashi H, Watanabe Y, Sawamura K, Fukui N, Watanabe J, Kitajima T, Yamanouchi Y, Iwata N, Mizukami K, Hori T, Shimoda K, Ujike H, Ozaki N, Iijima K, Takemura K, Aoshima H, Someya T: Diagnostic classification of schizophrenia by neural network analysis of blood-based gene expression signatures. Schizophr Res, 119, 210-218 (2010)
  22. Ohnuma T, Shibata N, Baba H, Ohi K, Yasuda Y, Nakamura Y, Okochi T, Naitoh H, Hashimoto R, Iwata N, Ozaki N, Takeda M, Arai H: No association between DAO and schizophrenia in a Japanese patient population: a multicenter replication study. Schizophr Res, 118, 300-302 (2010)
  23. Ohi K, Hashimoto R, Yasuda Y, Yoshida T, Takahashi H, Iike N, Iwase M, Kamino K, Ishii R, Kazui H, Fukumoto M, Takamura H, Yamamori H, Azechi M, Ikezawa K, Tanimukai H, Tagami S, Morihara T, Okochi M, Yamada K, Numata S, Ikeda M, Tanaka T, Kudo T, Ueno S, Yoshikawa T, Ohmori T, Iwata N, Ozaki N, Takeda M: The chitinase 3-like 1 gene and schizophrenia: Evidence from a multi-center case-control study and meta-analysis. Schizophr Res, 116, 126-132 (2010)
  24. Kushima I, Aleksic B, Ito Y, Nakamura Y, Nakamura K, Mori N, Kikuchi M, Inada T, Kunugi H, Nanko S, Kato T, Yoshikawa T, Ujike H, Suzuki M, Iwata N, Ozaki N: Association study of ubiquitin-specific peptidase 46 (USP46) with bipolar disorder and schizophrenia in a Japanese population. J Hum Genet, 55, 133-136 (2010)
  25. Kushima I, Aleksic B, Ikeda M, Yamanouchi Y, Kinoshita Y, Ito Y, Nakamura Y, Inada T, Iwata N, Ozaki N: Association study of bromodomain-containing 1 gene with schizophrenia in Japanese population. Am J Med Genet B Neuropsychiatr Genet, 153B, 786-791 (2010)
  26. Ishiguro H, Horiuchi Y, Ishikawa M, Koga M, Imai K, Suzuki Y, Morikawa M, Inada T, Watanabe Y, Takahashi M, Someya T, Ujike H, Iwata N, Ozaki N, Onaivi ES, Kunugi H, Sasaki T, Itokawa M, Arai M, Niizato K, Iritani S, Naka I, Ohashi J, Kakita A, Takahashi H, Nawa H, Arinami T: Brain Cannabinoid CB2 Receptor in Schizophrenia. Biol Psychiatry, 67, 974-982 (2010)
  27. Ikeda M, Tomita Y, Mouri A, Koga M, Okochi T, Yoshimura R, Yamanouchi Y, Kinoshita Y, Hashimoto R, Williams H.J, Takeda M, Nakamura J, Nabeshima T, Owen M.J, O'Donovan M.C, H. Honda, Arinami T, Ozaki N, Iwata N: Identification of Novel Candidate Genes for Treatment Response to Risperidone and Susceptibility for Schizophrenia: Integrated Analysis Among Pharmacogenomics, Mouse Expression, and Genetic Case-Control Association Approaches. Biol Psychiatry, 1, 67, 263-269 (2010)
  28. Ikeda M, Aleksic B, Kirov G, Kinoshita Y, Yamanouchi Y, Kitajima T, Kawashima K, Okochi T, Kishi T, Zaharieva I, Owen MJ, O'Donovan MC, Ozaki N, Iwata N: Copy number variation in schizophrenia in the Japanese population. Biol Psychiatry, 67, 283-286 (2010)
  29. Iidaka T, Saito DN, Komeda H, Mano Y, Kanayama N, Osumi T, Ozaki N, Sadato N: Transient Neural Activation in Human Amygdala Involved in Aversive Conditioning of Face and Voice. J Cogn Neurosci, 22, 2074-2085 (2010)
  30. Aleksic B, Kushima I, Ito Y, Nakamura Y, Ujike H, Suzuki M, Inada T, Hashimoto R, Takeda M, Iwata N, and Ozaki N: Genetic association study of KREMEN1 and DKK1 and schizophrenia in a Japanese population. Schizophr Res, 118, 113-117 (2010)
  31. Arai S, Shibata H, Sakai M, Ninomiya H, Iwata N, Ozaki N, Fukumaki Y: Association analysis of the glutamic acid decarboxylase 2 and the glutamine synthetase genes (gad2, glul) with schizophrenia. Psychiatr Genet, 19, 6-13 (2009)
  32. Kawashima K, Ikeda M, Kishi T, Kitajima T, Yamanouchi Y, Kinoshita Y, Okochi T, Aleksic B, Tomita M, Okada T, Kunugi H, Inada T, Ozaki N, Iwata N: Bdnf is not associated with schizophrenia: Data from a japanese population study and meta-analysis. Schizophr Res, 112, 72-79 (2009)
  33. Kishi T, Ikeda M, Kitajima T, Yamanouchi Y, Kinoshita Y, Kawashima K, Okochi T, Okumura T, Tsunoka T, Inada T, Ozaki N, Iwata N: Association analysis of functional polymorphism in estrogen receptor alpha gene with schizophrenia and mood disorders in the japanese population. Psychiatr Genet, 19, 217-218 (2009)
  34. Kishi T, Tsunoka T, Ikeda M, Kawashima K, Okochi T, Kitajima T, Kinoshita Y, Okumura T, Yamanouchi Y, Inada T, Ozaki N, Iwata N: Serotonin 1a receptor gene and major depressive disorder: An association study and meta-analysis. J Hum Genet, 54, 629-633 (2009)
  35. Kishi T, Kitajima T, Ikeda M, Yamanouchi Y, Kinoshita Y, Kawashima K, Okochi T, Okumura T, Tsunoka T, Ozaki N, Iwata N: Clock may predict the response to fluvoxamine treatment in japanese major depressive disorder patients. Neuromolecular Med, 11, 53-57 (2009)
  36. Kubota K, Inoue K, Hashimoto R, Kumamoto N, Kosuga A, Tatsumi M, Kamijima K, Kunugi H, Iwata N, Ozaki N, Takeda M, Tohyama M: Tumor necrosis factor receptor-associated protein 1 regulates cell adhesion and synaptic morphology via modulation of n-cadherin expression. J Neurochem, 110, 496-508 (2009)
  37. Ohi K, Hashimoto R, Yasuda Y, Yoshida T, Takahashi H, Iike N, Fukumoto M, Takamura H, Iwase M, Kamino K, Ishii R, Kazui H, Sekiyama R, Kitamura Y, Azechi M, Ikezawa K, Kurimoto R, Kamagata E, Tanimukai H, Tagami S, Morihara T, Ogasawara M, Okochi M, Tokunaga H, Numata S, Ikeda M, Ohnuma T, Ueno S, Fukunaga T, Tanaka T, Kudo T, Arai H, Ohmori T, Iwata N, Ozaki N, Takeda M: Association study of the g72 gene with schizophrenia in a japanese population: A multicenter study. Schizophr Res, 109, 80-85 (2009)
  38. Takahashi T, Suzuki M, Tsunoda M, Maeno N, Kawasaki Y, Zhou SY, Hagino H, Niu L, Tsuneki H, Kobayashi S, Sasaoka T, Seto H, Kurachi M, Ozaki N: The disrupted-in-schizophrenia-1 ser704cys polymorphism and brain morphology in schizophrenia. Psychiatry Res, 172, 128-135 (2009)
  39. Okumura T, Okochi T, Kishi T, Ikeda M, Kitajima T, Yamanouchi Y, Kinoshita Y, Kawashima K, Tsunoka T, Ujike H, Inada T, Ozaki N, Iwata N: No association between polymorphisms of neuronal oxide synthase 1 gene (nos1) and schizophrenia in a japanese population. Neuromolecular Med, 11, 123-127 (2009)
  40. Ueno H, Nishigaki Y, Kong QP, Fuku N, Kojima S, Iwata N, Ozaki N, Tanaka M: Analysis of mitochondrial DNA variants in japanese patients with schizophrenia. Mitochondrion, 9, 385-393 (2009)
  41. Watanabe Y, Nunokawa A, Kaneko N, Arinami T, Ujike H, Inada T, Iwata N, Kunugi H, Itokawa M, Otowa T, Ozaki N, Someya T: A two-stage case-control association study of padi2 with schizophrenia. J Hum Genet, 54, 430-432 (2009)
  42. Yoshimi A, Takahashi N, Saito S, Ito Y, Aleksic B, Usui H, Kawamura Y, Waki Y, Yoshikawa T, Kato T, Iwata N, Inada T, Noda Y, Ozaki N: Genetic analysis of the gene coding for darpp-32 (ppp1r1b) in japanese patients with schizophrenia or bipolar disorder. Schizophr Res, 100, 334-341 (2008)
  43. Yamasaki N, Maekawa M, Kobayashi K, Kajii Y, Maeda J, Soma M, Takao K, Tanda K, Ohira K, Toyama K, Kanzaki K, Fukunaga K, Sudo Y, Ichinose H, Ikeda M, Iwata N, Ozaki N, Suzuki H, Higuchi M, Suhara T, Yuasa S, Miyakawa T: Alpha-camkii deficiency causes immature dentate gyrus, a novel candidate endophenotype of psychiatric disorders. Mol Brain, 1, 6 (2008)
  44. Tanaka M, Kobayashi D, Murakami Y, Ozaki N, Suzuki T, Iwata N, Haraguchi K, Ieiri I, Kinukawa N, Hosoi M, Ohtani H, Sawada Y, Mine K: Genetic polymorphisms in the 5-hydroxytryptamine type 3b receptor gene and paroxetine-induced nausea. Int J Neuropsychopharmacol, 11, 261-267 (2008)
  45. Takahashi T, Suzuki M, Tsunoda M, Kawamura Y, Takahashi N, Maeno N, Kawasaki Y, Zhou SY, Hagino H, Niu L, Tsuneki H, Kobayashi S, Sasaoka T, Seto H, Kurachi M, Ozaki N: The association of genotypic combination of the drd3 and bdnf polymorphisms on the adhesio interthalamica and medial temporal lobe structures. Prog Neuropsychopharmacol Biol Psychiatry, 32, 1236-1242 (2008)
  46. Kawashima K, Kishi T, Ikeda M, Kitajima T, Yamanouchi Y, Kinoshita Y, Takahashi N, Saito S, Ohi K, Yasuda Y, Hashimoto R, Takeda M, Inada T, Ozaki N, Iwata N: No association between tagging snps of snare complex genes (stx1a, vamp2 and snap25) and schizophrenia in a japanese population. Am J Med Genet B Neuropsychiatr Genet, 147B, 1327-1331 (2008)
  47. Ji X, Takahashi N, Saito S, Ishihara R, Maeno N, Inada T, Ozaki N: Relationship between three serotonin receptor subtypes (htr3a, htr2a and htr4) and treatment-resistant schizophrenia in the japanese population. Neurosci Lett, 435, 95-98 (2008)
  48. Ito Y, Nakamura Y, Takahashi N, Saito S, Aleksic B, Iwata N, Inada T, Ozaki N: A genetic association study of the fxyd domain containing ion transport regulator 6 (fxyd6) gene, encoding phosphohippolin, in susceptibility to schizophrenia in a japanese population. Neurosci Lett, 438, 70-75 (2008)
  49. Ikeda M, Yamanouchi Y, Kinoshita Y, Kitajima T, Yoshimura R, Hashimoto S, O'Donovan MC, Nakamura J, Ozaki N, Iwata N: Variants of dopamine and serotonin candidate genes as predictors of response to risperidone treatment in first-episode schizophrenia. Pharmacogenomics, 9, 1437-1443 (2008)
  50. Ikeda M, Takahashi N, Saito S, Aleksic B, Watanabe Y, Nunokawa A, Yamanouchi Y, Kitajima T, Kinoshita Y, Kishi T, Kawashima K, Hashimoto R, Ujike H, Inada T, Someya T, Takeda M, Ozaki N, Iwata N: Failure to replicate the association between nrg1 and schizophrenia using japanese large sample. Schizophr Res, 101, 1-8 (2008)
  51. Ikeda M, Hikita T, Taya S, Uraguchi-Asaki J, Toyo-oka K, Wynshaw-Boris A, Ujike H, Inada T, Takao K, Miyakawa T, Ozaki N, Kaibuchi K, Iwata N: Identification of ywhae, a gene encoding 14-3-3epsilon, as a possible susceptibility gene for schizophrenia. Hum Mol Genet, 17, 3212-3222 (2008)
  52. Aleksic B, Ikeda M, Ishihara R, Saito S, Inada T, Iwata N, Ozaki N: No association between the oligodendrocyte-related gene plp1 and schizophrenia in the japanese population. J Hum Genet, 53, 863-866 (2008)
  53. Kuratomi G et al. Aberrant DNA methylation associated with bipolar disorder identified from discordant monozygotic twins. Mol. Psychiatry 13: 429-441 (2008)
  54. Ohnishi T et al. A Promoter Haplotype of the Inositol Monophosphatase 2 Gene (IMPA2) at 18p11.2 Confers a Possible Risk for Bipolar Disorder by Enhancing Transcription. Neuropsychopharmacology 32: 1727-1737 (2007)
  55. Matsuzawa D et al. Identification of Functional Polymorphisms in the Promoter Region of the Human PICK1 Gene and Their Association With Methamphetamine Psychosis. Am. J. Psychiatry 164: 1105-1114 (2007)
  56. Horiuchi Y et al. Support for association of the PPP3CC gene with schizophrenia. Mol. Psychiatry 12: 891-893 (2007)
  57. Hashimoto R et al. Pituitary adenylate cyclase-activating polypeptide is associated with schizophrenia. Mol. Psychiatry 12: 1026-1032 (2007)
  58. Ikeda M et al. Positive association of the serotonin 5-HT7 receptor gene with schizophrenia in a Japanese population. Neuropsychopharmacology 31: 866-871 (2006)
  59. Hashimoto R et al. Impact of the DISC1 Ser704Cys polymorphism on risk for major depression, brain morphology and ERK signaling. Hum. Mol. Genet. 15: 3024-3033 (2006)
  60. Ikeda M et al. Association Analysis of Chromosome 5 GABA(A) Receptor Cluster in Japanese Schizophrenia Patients. Biol. Psychiatry 58: 440-445 (2005)
  61. Arinami T et al. Genomewide high-density SNP linkage analysis of 236 Japanese families supports the existence of schizophrenia susceptibility Loci on chromosomes 1p, 14q, and 20p. Am. J. Hum. Genet. 77: 937-944 (2005)
  62. Iidaka T et al. A variant C178T in the regulatory region of the serotonin receptor gene HTR3A modulates neural activation in the human amygdala. J. Neurosci. 25: 6460-6466 (2005)
  63. Okada M et al. Modification of Human 5-HT2C Receptor Function by Cys23Ser, an Abundant, Naturally Occurring Amino Acid Substitution. Mol. Psychiatry 9: 55-64 (2004)
  64. Numakawa T et al. Evidence of novel neuronal functions of dysbindin, a susceptibility gene for schizophrenia. Hum. Mol. Genet. 13: 2699-2708 (2004)
  65. Iwata N et al. No Association With the Neuregulin 1 Haplotype to Japanese Schizophrenia. Mol. Psychiatry 9: 126-127 (2004)
  66. Ikeda M et al. Association of AKT1 with schizophrenia confirmed in a Japanese population. Biol. Psychiatry 56: 698-700 (2004)
  67. Ozaki N et al. Serotonin transporter missense mutation associated with a complex neuropsychiatric phenotype. Mol. Psychiatry 8: 933-936 (2003)
  68. Iwata N et al. Association of a 5-HT(5A) receptor polymorphism, Pro15Ser, to schizophrenia. Mol. Psychiatry 6: 217-219 (2001)
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  71. Ozaki N. et al. Two naturally occurring amino acid substitutions of the 5-HT2A receptor, similar prevalence in patients with seasonal affective disorder and controls. Biol. Psychiatry 40: 1267-1272 (1996)
  72. Malhotra AK et al. Lack of association between polymorphisms in the 5-HT2A receptor gene and the antipsychotic response to clozapine. Am. J. Psychiatry 153: 1092-1094 (1996)
  73. Ozaki N et al. Prevalence of seasonal difficulties in mood and behavior among Japanese civil servants. Am. J. Psychiatry 152: 1225-1227 (1995)

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