Analysis of molecular pathophysiology of schizophrenia using cognitive function and neuroimaging as an intermediate phenotype

2009 Fiscal Year Final Research Report

• Project/Area Number: 19390304
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Nagoya University
• Principal Investigator: OZAKI Norio Nagoya University, 大学院・医学系研究科, 教授 (40281480)
• Co-Investigator(Kenkyū-buntansha): IIDAKA Tetsuya 名古屋大学, 大学院・医学系研究科, 准教授 (70324366)
• Co-Investigator(Renkei-kenkyūsha): IWATA Nakao 藤田保健衛生大学, 医学部, 教授 (60312112)
• Project Period (FY): 2007 – 2009
• Keywords: 統合失調症 / ゲノム / 認知機能 / 神経画像 / 中間表現型

Research Abstract

We conducted the genetic association with neuroimaging data and response to a therapeutic drug instead of diagnosis to investigate the molecular pathophysiology of schizophrenia. As a result a neurotrophic factor gene showed the association with brain structure measured by neuroimaging technique. The therapeutic response to medication had association with dopaminergic genes and newly found genes. In addition, the analysis revealed the association between adverse events induced by medication and gabanergic genes.

Research Products

• [Journal Article] Diagnostic classification of schizophrenia by neural network analysis of blood-based gene expression signatures (2010)
  • Author(s): Takahashi, M., H. Hayashi, Y. Watanabe, K. Sawamura, N. Fukui, J. Watanabe, T. Kitajima, Y. Yamanouchi, N. Iwata, K. Mizukami, T. Hori, K. Shimoda, H. Ujike, N. Ozaki, K. Iijima, K. Takemura, H. Aoshima, T. Someya
  • Journal Title: Schizophr Res (in press)
  • Peer Reviewed
• [Journal Article] Association study of ubiquitin-specific peptidase 46 (USP46) with bipolar disorder and schizophrenia in a Japanese population (2010)
  • Author(s): Kushima, I., B. Aleksic, Y. Ito, Y. Nakamura, K. Nakamura, N. Mori, M. Kikuchi, T. Inada, H. Kunugi, S. Nanko, T. Kato, T. Yoshikawa, H. Ujike, M. Suzuki, N. Iwata, N. Ozaki
  • Journal Title: J Hum Genet (in press)
  • Peer Reviewed
• [Journal Article] Association study of bromodomain-containing 1 gene with schizophrenia in Japanese population (2010)
  • Author(s): Kushima, I., B. Aleksic, M. Ikeda, Y. Yamanouchi, Y. Kinoshita, Y. Ito, Y. Nakamura, T. Inada, N. Iwata, N. Ozaki
  • Journal Title: Am J Med Genet B Neuropsychiatr Genet (in press)
  • Peer Reviewed
• [Journal Article] Genetic association study of KREMEN1 and DKK1 and schizophrenia in a Japanese population (2010)
  • Author(s): Aleksic, B., I. Kushima, Y. Ito, Y. Nakamura, H. Ujike, M. Suzuki, T. Inada, R. Hashimoto, M. Takeda, N. Iwata, N. Ozaki
  • Journal Title: Schizophr Res (in press)
  • Peer Reviewed
• [Journal Article] 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 (2010)
  • Author(s): Ikeda, M., Y. Tomita, A. Mouri, M. Koga, T. Okochi, R. Yoshimura, Y. Yamanouchi, Y. Kinoshita, R. Hashimoto, H.J. Williams, M. Takeda, J. Nakamura, T. Nabeshima, M.J. Owen, M.C. O'Donovan, H. Honda, T. Arinami, N. Ozaki, N. Iwata
  • Journal Title: Biol Psychiatry 67(3) Pages: 263-9
  • Peer Reviewed
• [Journal Article] Copy number variation in schizophrenia in the Japanese population (2010)
  • Author(s): Ikeda, M., B. Aleksic, G. Kirov, Y. Kinoshita, Y. Yamanouchi, T. Kitajima, K. Kawashima, T. Okochi, T. Kishi, I. Zaharieva, M.J. Owen, M.C. O'Donovan, N. Ozaki, N. Iwata
  • Journal Title: Biol Psychiatry 67(3) Pages: 283-6
  • Peer Reviewed
• [Journal Article] The Disrupted-in-Schizophrenia-1 Ser704Cys polymorphism and brain morphology in schizophrenia (2009)
  • Author(s): Takahashi, T., M. Suzuki, M. Tsunoda, N. Maeno, Y. Kawasaki, S.Y. Zhou, H. Hagino, L. Niu, H. Tsuneki, S. Kobayashi, T. Sasaoka, H. Seto, M. Kurachi, N. Ozaki
  • Journal Title: Psychiatry Res 172(2) Pages: 128-35
  • Peer Reviewed
• [Journal Article] BDNF is not associated with schizophrenia: data from a Japanese population study and meta-analysis (2009)
  • Author(s): Kawashima, K., M. Ikeda, T. Kishi, T. Kitajima, Y. Yamanouchi, Y. Kinoshita, T. Okochi, B. Aleksic, M. Tomita, T. Okada, H. Kunugi, T. Inada, N. Ozaki, N. Iwata
  • Journal Title: Schizophr Res 112(1-3) Pages: 72-9
  • Peer Reviewed
• [Journal Article] Genetic analysis of the gene coding for DARPP-32 (PPP1R1B) in Japanese patients with schizophrenia or bipolar disorder (2008)
  • Author(s): Yoshimi, A., N. Takahashi, S. Saito, Y. Ito, B. Aleksic, H. Usui, Y. Kawamura, Y. Waki, T. Yoshikawa, T. Kato, N. Iwata, T. Inada, Y. Noda, N. Ozaki
  • Journal Title: Schizophr Res 100(1-3) Pages: 334-41
  • Peer Reviewed
• [Journal Article] An association study of tachykinin receptor 3 gene with schizophrenia in the Japanese population (2008)
  • Author(s): Saito, S., N. Takahashi, N. Maeno, Y. Ito, B. Aleksic, H. Usui, T. Iidaka, T. Inada, N. Ozaki
  • Journal Title: Neuroreport 19(4) Pages: 471-473
  • Peer Reviewed
• [Journal Article] Aberrant DNA methylation associated with bipolar disorder identified from discordant monozygotic twins (2008)
  • Author(s): Kuratomi, G., K. Iwamoto, M. Bundo, I. Kusumi, N. Kato, N. Iwata, N. Ozaki, T. Kato
  • Journal Title: Mol Psychiatry 13(4) Pages: 429-41
  • Peer Reviewed
• [Journal Article] The Dysbindin Gene (DTNBP1) Is Associated with Methamphetamine Psychosis (2008)
  • Author(s): Kishimoto, M., H. Ujike, Y. Motohashi, Y. Tanaka, Y. Okahisa, T. Kotaka, M. Harano, T. Inada, M. Yamada, T. Komiyama, T. Hori, Y. Sekine, N. Iwata, I. Sora, M. Iyo, N. Ozaki, S. Kuroda
  • Journal Title: Biol Psychiatry 63(2) Pages: 191-196
  • Peer Reviewed
• [Journal Article] Relationship between three serotonin receptor subtypes (HTR3A, HTR2A and HTR4) and treatment-resistant schizophrenia in the Japanese population (2008)
  • Author(s): Ji, X., N. Takahashi, S. Saito, R. Ishihara, N. Maeno, T. Inada, N. Ozaki
  • Journal Title: Neurosci Lett 435(2) Pages: 95-8
  • Peer Reviewed
• [Journal Article] Pathway-based association analysis of genome-wide screening data suggest that genes associated with the gamma-aminobutyric acid receptor signaling pathway are involved in neuroleptic-induced, treatment-resistant tardive dyskinesia (2008)
  • Author(s): Inada, T., M. Koga, H. Ishiguro, Y. Horiuchi, A. Syu, T. Yoshio, N. Takahashi, N. Ozaki, T. Arinami
  • Journal Title: Pharmacogenet Genomics 18(4) Pages: 317-323
  • Peer Reviewed
• [Journal Article] Variants of dopamine and serotonin candidate genes as predictors of response to risperidone treatment in first-episode schizophrenia (2008)
  • Author(s): Ikeda, M., Y. Yamanouchi, Y. Kinoshita, T. Kitajima, R. Yoshimura, S. Hashimoto, M.C. O'Donovan, J. Nakamura, N. Ozaki, N. Iwata
  • Journal Title: Pharmacogenomics 9(10) Pages: 1437-4
  • Peer Reviewed
• [Journal Article] Failure to replicate the association between NRG1 and schizophrenia using Japanese large sample (2008)
  • Author(s): Ikeda, M., N. Takahashi, S. Saito, B. Aleksic, Y. Watanabe, A. Nunokawa, Y. Yamanouchi, T. Kitajima, Y. Kinoshita, T. Kishi, K. Kawashima, R. Hashimoto, H. Ujike, T. Inada, T. Someya, M. Takeda, N. Ozaki, N. Iwata
  • Journal Title: Schizophr Res 101(1-3) Pages: 1-8
  • Peer Reviewed
• [Journal Article] Identification of YWHAE, a gene encoding 14-3-3epsilon, as a possible susceptibility gene for schizophrenia (2008)
  • Author(s): Ikeda, M., T. Hikita, S. Taya, J. Uraguchi-Asaki, K. Toyo-oka, A. Wynshaw-Boris, H. Ujike, T. Inada, K. Takao, T. Miyakawa, N. Ozaki, K. Kaibuchi, N. Iwata
  • Journal Title: Hum Mol Genet 7(20) Pages: 3212-22
  • Peer Reviewed
• [Journal Article] N. o association between the oligodendrocyte-related gene PLP1 and schizophrenia in the Japanese population (2008)
  • Author(s): Aleksic, B., M. Ikeda, R. Ishihara, S. Saito, T. Inada, N. Iwata, N. Ozaki
  • Journal Title: J Hum Genet 53(9) Pages: 863-6
  • Peer Reviewed
• [Journal Article] Identification of Functional Polymorphisms in the Promoter Region of the Human PICK1 Gene and Their Association With Methamphetamine Psychosis (2007)
  • Author(s): Matsuzawa, D., K. Hashimoto, R. Miyatake, Y. Shirayama, E. Shimizu, K. Maeda, Y. Suzuki, Y. Mashimo, Y. Sekine, T. Inada, N. Ozaki, N. Iwata, M. Harano, T. Komiyama, M. Yamada, I. Sora, H. Ujike, A. Hata, A. Sawa, M. Iyo
  • Journal Title: Am J Psychiatry 164(7) Pages: 1105-14
  • Peer Reviewed
• [Journal Article] Association of SOX10 with schizophrenia in the Japanese population (2007)
  • Author(s): Maeno, N., N. Takahashi, S. Saito, X. Ji, R. Ishihara, N. Aoyama, A. Branko, H. Miura, M. Ikeda, T. Suzuki, T. Kitajima, Y. Yamanouchi, Y. Kinoshita, N. Iwata, T. Inada, N. Ozaki
  • Journal Title: Psychiatr Genet 17(4) Pages: 227-231
  • Peer Reviewed
• [Journal Article] Association study between the transferrin gene and schizophrenia in the Japanese population (2007)
  • Author(s): Maeno, N., N. Takahashi, S. Saito, X. Ji, A. Branko, R. Ishihara, K. Yoshida, T. Inada, T. Iidaka, N. Ozaki
  • Journal Title: Neuroreport 18(5) Pages: 517-20
  • Peer Reviewed
• [Journal Article] No association between the glutamate decarboxylase 67 gene (GAD1) and schizophrenia in the Japanese population (2007)
  • Author(s): Ikeda, M., N. Ozaki, Y. Yamanouchi, T. Suzuki, T. Kitajima, Y. Kinoshita, T. Inada, N. Iwata
  • Journal Title: Schizophr Res 91(1-3) Pages: 22-6
  • Peer Reviewed
• [Journal Article] Possible association of beta-arrestin 2 gene with methamphetamine use disorder, but not schizophrenia (2007)
  • Author(s): Ikeda, M., N. Ozaki, T. Suzuki, T. Kitajima, Y. Yamanouchi, Y. Kinoshita, T. Kishi, Y. Sekine, M. Iyo, M. Harano, T. Komiyama, M. Yamada, I. Sora, H. Ujike, T. Inada, N. Iwata
  • Journal Title: Genes Brain Behav 6(1) Pages: 107-12
  • Peer Reviewed
• [Journal Article] Pituitary adenylate cyclase-activating polypeptide is associated with schizophrenia (2007)
  • Author(s): Hashimoto, R., H. Hashimoto, N. Shintani, S. Chiba, S. Hattori, T. Okada, M. Nakajima, K. Tanaka, N. Kawagishi, K. Nemoto, T. Mori, T. Ohnishi, H. Noguchi, H. Hori, T. Suzuki, N. Iwata, N. Ozaki, T. Nakabayashi, O. Saitoh, A. Kosuga, M. Tatsumi, K. KamijiHashimoto, R., H. Hashimoto, N. Shintani, S
  • Journal Title: Mol Psychiatry 12(11) Pages: 1026-1032
  • Peer Reviewed
• [Journal Article] Gap junction coding genes and schizophrenia: a genetic association study (2007)
  • Author(s): Aleksic, B., R. Ishihara, N. Takahashi, N. Maeno, X. Ji, S. Saito, T. Inada, N. Ozaki
  • Journal Title: J Hum Genet 52(6) Pages: 498-501
  • Peer Reviewed
• [Presentation] DISC1-interacting molecule and schizophrenia (2009)
  • Author(s): Ozaki, N
  • Organizer: in 9th World Congress of Biological Psychiatry: Symposium Genetic stratetegies in the search for genes in schizophrenia
  • Place of Presentation: Paris, France
  • Year and Date: 20090628-20090702
• [Presentation] Glia-related gene and schizophrenia: Invited lecture. in The Third Dual Congress on (2008)
  • Author(s): Ozaki, N
  • Organizer: Psychiatry and the Neurosciences
  • Place of Presentation: Athens
  • Year and Date: 20081016-20081019
• [Presentation] 統合失調症モデル動物に臨床医が望むこと (2008)
  • Author(s): 尾崎紀夫
  • Organizer: in第18回日本臨床精神神経薬理学会・第38回日本神経精神薬理学会合同年会
  • Place of Presentation: 東京
  • Year and Date: 20081001-20081003
• [Presentation] From Gene to Phenotype in Schizophrenia: Invited lecture (2008)
  • Author(s): Ozaki, N
  • Organizer: in 2nd WFSBP Asia-Pacific Congress
  • Place of Presentation: Toyama
  • Year and Date: 20080910-20080913
• [Presentation] Endophenotype Approach of Mental Disorders: Bridging between Genotype and Phenotype (2008)
  • Author(s): Ozaki, N
  • Organizer: in 2008 International Conference on Pharmacogenomics Symposium :New Paradigm of Pharmacogonomics: to be alone or together Invited
  • Place of Presentation: Busan, Korea
  • Year and Date: 20080409-20080412
• [Presentation] DISC1-interacting molecules and pathogenesis of schizophrenia:Candidate gene approach (2007)
  • Author(s): Ozaki, N., , M. Ikeda, S. Taya, K. Kaibuchi, N. Iwata
  • Organizer: in 2nd WFSBP International Congress of Biological Psychiatry :Symposium Pathogenesis of Schizophrenia
  • Place of Presentation: Chilli
  • Year and Date: 20070417-20070421