Integrative approach toward understanding impaired glutamatergic neurotransmission in schizophrenia

2008 Fiscal Year Final Research Report

• Project/Area Number: 18390319
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: The University of Tokyo
• Principal Investigator: KASAI Kiyoto The University of Tokyo, 医学部・附属病院, 教授 (80322056)
• Co-Investigator(Renkei-kenkyūsha): HASHIMOTO Kenji 千葉大学, 社会精神保健教育研究センター, 教授 (10189483) ; SASAKI Tsukasa 東京大学, 学生相談ネットワーク本部, 教授 (50235256) ; AOKI Shigeki 順天堂大学, 医学部, 教授 (80222470) ; ABE Osamu 東京大学, 医学部・附属病院, 准教授 (50302716) ; YAMADA Haruyasu 帝京大学, ちば総合医療センター, 准教授 (70359610)
• Project Period (FY): 2006 – 2008
• Keywords: 脳・神経 / 遺伝子 / 神経画像 / 中間表現型 / グルタミン酸

Research Abstract

統合失調症におけるグルタミン酸神経伝達系の異常を明らかにするために、遺伝子、血液生化学マーカー、神経画像計測を統合したアプローチを行った。その結果、統合失調症において、グルタミン酸神経伝達系のプローブとなる各指標の異常が相互関連していることを明らかにした。この結果は、統合失調症のグルタミン酸神経伝達系異常仮説に依拠した補助診断法開発や分子標的治療研究への基盤となるものである。

Research Products

• [Journal Article] Tract-specific analysis of the superior occipitofrontal fasciculus in schizophrenia (2008)
  • Author(s): Kunimatsu N, Aoki S, Kunimatsu A, Yoshida M, Abe O, Yamada H, Masutani Y, Kasai K, Yamasue H, Ohtsu H, Ohtomo K
  • Journal Title: Psychiatry Res Neuroimaging 164 Pages: 198-205
  • Peer Reviewed
• [Journal Article] Association and interaction analyses of NRG1 and ERBB4 genes with schizophrenia in a Japanese population (2008)
  • Author(s): Shiota S, Tochigi M, Shimada H, Ohashi J, Kasai K, Kato N, Tokunaga K, Sasaki T
  • Journal Title: J Hum Genet 53 Pages: 929-935
  • Peer Reviewed
• [Journal Article] Disrupted integrity of the fornix is associated with impaired memory organization in schizophrenia (2008)
  • Author(s): Takei K, Yamasue H, Abe O, Yamada H, Inoue H, Suga M, Sekita K, Sasaki H, Rogers MA, Aoki S, Kasai K
  • Journal Title: Schizophr Res 103 Pages: 52-61
  • Peer Reviewed
• [Journal Article] Reduced frontopolar activation during verbal fluency task in schizophrenia : a multi-channel near-infrared spectroscopy study (2008)
  • Author(s): Takizawa R, Kasai K, Kawakubo Y, Marumo K, Kawasaki S, Yamasue H, Fukuda M
  • Journal Title: Schizophr Res 99 Pages: 250-262
  • Peer Reviewed
• [Journal Article] Increased positive thought disorder with illness duration in patients with schizophrenia (2007)
  • Author(s): Maeda K, Kasai K, Uetsuki M, Araki T, Yamasue H, Hata A, Kato N, Iwanami A
  • Journal Title: Psychiatry Clin Neurosci 61 Pages: 687-690
  • Peer Reviewed
• [Journal Article] Reduced planum temporale volume and delusional behavior in patients with schizophrenia (2007)
  • Author(s): Yamasaki S, Yamasue H, Abe O, Yamada H, Iwanami A, Hirayasu Y, Nakamura M, Furukawa S, Rogers MA, Tanno Y, Aoki S, Kato N, Kasai K
  • Journal Title: Eur Arch Psychiatry Clin Neurosci 257 Pages: 318-324
  • Peer Reviewed
• [Journal Article] Phonetic mismatch negativity predicts social skills acquisition in schizophrenia (2007)
  • Author(s): Kawakubo Y, Kamio S, Nose T, Iwanami A, Nakagome K, Fukuda M, Kato N, Rogers MA, Kasai K
  • Journal Title: Psychiatry Res 152 Pages: 261-265
  • Peer Reviewed
• [Journal Article] Progressive and interrelated functional and structural evidence for post-onset brain reduction in schizophrenia (2007)
  • Author(s): Salisbury DF, Kuroki N, Kasai K, Shenton ME, McCarley RW
  • Journal Title: Arch Gen Psychiatry 64 Pages: 521-529
  • Peer Reviewed
• [Journal Article] No association between the metabotropic glutamate receptor 3 gene(GRM3)and schizophrenia in a Japanese population (2006)
  • Author(s): Tochigi M, Suga M, Ohashi J, Otowa T, Yamasue H, Kasai K, Kato T, Okazaki Y, Kato N, Sasaki T
  • Journal Title: Schizophr Res 88 Pages: 260-264
  • Peer Reviewed
• [Journal Article] Auditory P300 latency prolongation with age in schizophrenia : gender and subcomponent effects (2006)
  • Author(s): Araki T, Kasai K, Kirihara K, Yamasue H, Kato N, Kudo N, Nakagome K, Iwanami A
  • Journal Title: Schizophr Res 88 Pages: 217-221
  • Peer Reviewed
• [Journal Article] No evidence for an associatin between the BDNF Val66Met polymorphism and schizophrenia or personality traits (2006)
  • Author(s): Tochigi M, Otowa T, Suga M, Rogers M, Minato T, Yamasue H, Kasai K, Kato N, Sasaki T
  • Journal Title: Schizophr Res 87 Pages: 45-47
  • Peer Reviewed
• [Journal Article] Support for an association between mismatch negativity and social functioning in schizophrenia (2006)
  • Author(s): Kawakubo Y, Kasai K
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry 30 Pages: 1367-1368
  • Peer Reviewed
• [Journal Article] Procedural memory predicts social skills in persons with schizophrenia (2006)
  • Author(s): Kawakubo Y, Rogers MA, Kasai K
  • Journal Title: J Nerv Ment Dis 194 Pages: 625-627
  • Peer Reviewed
• [Journal Article] Effect of subjective reasoning and neurocognition on medication adherence for persons with schizophrenia (2006)
  • Author(s): Maeda K, Kasai K, Watanabe A, Henomatsu K, Rogers MA, Kato N
  • Journal Title: Psychiatr Serv 57 Pages: 1203-1205
  • Peer Reviewed
• [Journal Article] Phonetic mismatch negativity predicts verbal memory deficits in schizophrenia (2006)
  • Author(s): Kawakubo Y, Kasai K, Kudo N, Rogers MA, Nakagome K, Itoh K, Kato N
  • Journal Title: Neuroreport 17 Pages: 1043-1046
  • Peer Reviewed
• [Journal Article] The effect of perospirone on auditory P300 in schizophrenia : a preliminary study (2006)
  • Author(s): Araki T, Kasai K, Rogers MA, Kato N, Iwanami A
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry 30 Pages: 1083-1090
  • Peer Reviewed
• [Journal Article] Perospirone in the treatment of schizophrenia : effect on verbal memory organization (2006)
  • Author(s): Araki T, Yamasue H, Sumiyoshi T, Kuwabara H, Suga M, Iwanami A, Kato N, Kasai K
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry 30 Pages: 204-208
  • Peer Reviewed
• [Journal Article] Structural disruption of the dorsal cingulum bundle is associated with impaired Stroop performance in patients with schizophrenia
  • Author(s): Takei K, Yamasue H, Abe O, Yamada H, Inoue H, Suga M, Muroi M, Sasaki H, Aoki S, Kasai K
  • Journal Title: Schizophr Res (in press)
  • Peer Reviewed
• [Journal Article] Association study between auditory P3a/P3b event-related potentials and thought disorder in schizophrenia
  • Author(s): Kirihara K, Araki T, Uetsuki M, Yamasue H, Hata A, Rogers MA, Iwanami A, Kasai K
  • Journal Title: Brain Imaging Behav (in press)
  • Peer Reviewed
• [Journal Article] Association between catechol-o-methyltrasferase val108/158met genotype and prefrontal hemodynamic response in schizophrenia
  • Author(s): Takizawa R, Tochigi M, Kawakubo Y, Marumo K, Sasaki T, Fukuda M, Kasai K
  • Journal Title: PLoS ONE (in press)
  • Peer Reviewed
• [Journal Article] Association between sigma-1 receptor gene polymorphism and prefrontal hemodynamic response induced by cognitive activation in schizophrenia
  • Author(s): Takizawa R, Hashimoto K, Tochigi M, Kawakubo Y, Marumo K, Sasaki T, Fukuda M, Kasai K
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry (in press)
  • Peer Reviewed
• [Presentation] Mismatch negativity as a functional probe for glutamatergic/synaptic dysfunction in schizophrenia (2008)
  • Author(s): Kasai K
  • Organizer: World Federation of Societies of Biological Psychiatry 2^<nd> WFSBP Asia-Pacific Congress and Annual Meeting of JSBP
  • Place of Presentation: Toyama, Japan[Symposium]
  • Year and Date: 2008-09-12
• [Presentation] Phonetic magnetic mismatch field (MMF) as a functional probe for glutamatergic /synaptic dysfunction in schizophrenia (2007)
  • Author(s): Kasai K
  • Organizer: International Society for the Advancement of Clinical Magnetoencephalography
  • Place of Presentation: Matsushima, Japan[Symposium]
  • Year and Date: 2007-08-28
• [Presentation] a probe for glutamatergic dysfunction in schizophrenia (2006)
  • Author(s): Kasai K
  • Organizer: 14^<th> Biennal Congress on International Pharmaco-EEG Society(Mismatch negativity (MMN))
  • Place of Presentation: Awaji, Japan[invited lecture]
  • Year and Date: 2006-09-07
• [Book] 精神疾患と脳画像、専門医のための精神科臨床リュミエール2(統合失調症の脳構造) (2008)
  • Author(s): 井上秀之、山末英典、笠井清登
  • Publisher: 中山書店、東京
• [Book] 精神疾患の脳画像解析・診断学(笠井清登編) (2008)
  • Author(s): 平安良雄
  • Publisher: 南山堂、東京
• [Book] Psychology and Schizophrenia(Pletson JE)(Nova Science Publishers, Hauppauge, NY, USAUsing advanced neuroimaging techniques toward understanding schizophrenia) (2007)
  • Author(s): Yamasue H, Kasai K, Fukuda M
  • Publisher: Nova Science Publishers, Hauppauge, NY, USA
• [Book] Psychology and Schizophrenia(Pletson JE,)(Executive deficits in schizophrenia and mood disorder) (2007)
  • Author(s): Rogers M, Kasai K, Fukuda M
  • Publisher: Nova Science Publishers Publishers, Hauppauge, NY, USA
• [Book] 統合失調症の治療-基礎と臨床-(脳の電気生理学的評価) (2007)
  • Author(s): 笠井清登
• [Book] TEXT 精神医学、コラム(精神疾患のNIRS) (2007)
  • Author(s): 滝沢龍、笠井清登
  • Publisher: 南山堂、東京
• [Book] 認知療法2006(貝谷久宣)(統合失調症における非薬理学的介入の効果の脳基盤) (2006)
  • Author(s): 笠井清登
  • Publisher: 星和書店
• [Book] EBM精神疾患の治療2006-2007, 各論、I統合失調症(器質性変化は臨床症状や社会的予後と関連するか?) (2006)
  • Author(s): 管心、山末英典、笠井清登
  • Publisher: 中外医学社、東京
• [Book] EBM精神疾患の治療2006-2007, 各論、I統合失調症(どこまで脳器質性障害と言えるか?) (2006)
  • Author(s): 山末英典、管心、笠井清登
  • Publisher: 中外医学社、東京
• [Book] 専門医のための精神科臨床リュミエール7(初回エピソード統合失調症の画像・神経生理)
  • Author(s): 高野洋輔、切原賢治、笠井清登
  • Publisher: 中山書店、東京(印刷中)
• [Book] 精神疾患とNIRS(福田正人)(統合失調症・自閉症の前頭葉機能障害とNIRSの臨床応用)
  • Author(s): 滝沢龍、川久保友紀、桑原斉、笠井清登
  • Publisher: 中山書店、東京(印刷中)
• [Remarks] 研究室ホームページ
  • URL: http://npsy.umin.jp/study/cp.html