Identification of suicidal-behavior related genes in the HPA axis regulating stress response

• Project/Area Number: 21791132
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Psychiatric science
• Research Institution: Kobe University
• Principal Investigator: HISHIMOTO Akitoyo Kobe University, 大学院・医学研究科, 講師 (50529526)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 臨床精神分子遺伝学 / 自殺 / FKBP5 / NOS1 / 統合失調症 / 死後脳 / polymorphism / アレキシサイミア / 性差 / TPH1 / TPH2 / ALDH2 / ADH1B / RGS2

Research Abstract

We explored a positive association of suicidal behavior with certain haplotypes of FKBP5 gene which regulates the hypothalamo-pituitary-adrenal axis in stress response. We additionally explored associations of suicidal behavior with polymorphisms of ALDH2 and NOS1 genes. We also found a positive association of schizophrenia with polymorphisms of NOS1 gene. Our findings suggest that suicidal behavior is involved in the genetic vulnerability and that certain polymorphisms might be useful for a biomarker of suicidal behavior.

Research Products

• [Journal Article] Association study of EP1 gene polymorphisms with suicide completers in the Japanese population. (2011)
  • Author(s): Cui H, Supriyanto I, Sasada T, Shiroiwa K, Fukutake M, Shirakawa O, Asano M, Ueno Y, Nagasaki Y, Hishimoto A (correspondent)
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry epub
  • Peer Reviewed
• [Journal Article] Alexithymia and its Relationships with Eating Behavior, Self-esteem, and Body esteem in College Women (2011)
  • Author(s): Sasai K, Tanaka K, Hishimoto A(correspondent)
  • Journal Title: Kobe Journal of Medical Sciences in press
  • NAID: 110009587652
  • Peer Reviewed
• [Journal Article] Association of FKBP5 gene haplotypes with completed suicide in the Japanese population. (2011)
  • Author(s): Supriyanto I, Sasada T, Fukutake M, Asano M, Ueno Y, Nagasaki Y, Shirakawa O, Hishimoto A (correspondent)
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry 35(1) Pages: 252-6
  • Peer Reviewed
• [Journal Article] Association of FKBP5 gene haplotypes with completed suicide in the Japanese population. (2011)
  • Author(s): Supriyanto I, et al
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry Volume: 35(1) Pages: 252-256
  • Peer Reviewed
• [Journal Article] Alexithymia and its Relationships with Eating Behavior, Self-esteem, and Body esteem in College Women (2011)
  • Author(s): Sasai K, et al
  • Journal Title: Kobe Journal of Medical Sciences Volume: (In press)
  • Peer Reviewed
• [Journal Article] A putative cis-acting polymorphism in the NOS1 gene is associated with schizophrenia and NOS1 immunoreactivity in the postmortem brain. (2010)
  • Author(s): Huxing Cui, Naoki Nishiguchi, Masaya Yanagi, Fukutake M, Kentaro Mouri, Noboru Kitamura, Takeshi Hashimoto, Osamu Shirakawa, Akitoyo Hishimoto(correspondent).
  • Journal Title: Schizophrenia Research 121(1-3) Pages: 172-178
  • Peer Reviewed
• [Journal Article] A common polymorphism in the 3'-UTR of the NOS1 gene was associated with completed suicides in Japanese male population. (2010)
  • Author(s): Huxing Cui, Irwan Supriyanto, Migiwa Asano, Yasuhiro Ueno, Yasushi Nagasaki, Naoki Nishiguchi, Osamu Shirakawa, Akitoyo Hishimoto(correspondent).
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry 34(6) Pages: 992-996
  • Peer Reviewed
• [Journal Article] Common genetic variations in TPH1/TPH2 genes are not associated with schizophrenia in Japanese population. (2010)
  • Author(s): Kyoichi Shiroiwa, Akitoyo Hishimoto(correspondent), Kentaro Mouri, Fukutake M, Irwan Supriyanto, Naoki Nishiguchi, Osamu Shirakawa, Kiyoshi Maeda.
  • Journal Title: Neuroscience Letters 472(3) Pages: 194-198
  • Peer Reviewed
• [Journal Article] Alcohol and aldehyde dehydrogenase polymorphisms and risk for suicide ; A preliminary observation in the male Japanese population. (2010)
  • Author(s): Akitoyo Hishimoto(correspondent), Kentaro Mouri, Fukutake M, Yasushi Nagasaki, Migiwa Asano, Yasuhiro Ueno, Naoki Nishiguchi, Osamu Shirakawa
  • Journal Title: Genes, Brain and Behavior 9(5) Pages: 498-502
  • Peer Reviewed
• [Journal Article] Association Study of RGS2 Gene Polymorphisms with Panic Disorder in Japanese. (2010)
  • Author(s): Mouri K, Hishimoto A(correspondent), Fukutake M, Shirakawa O, Nishiguchi N, Maeda K.
  • Journal Title: Kobe Journal of Medical Sciences 55(5) Pages: 116-121
  • NAID: 110007614321
  • Peer Reviewed
• [Journal Article] 細胞接着因子と精神疾患 (2010)
  • Author(s): 菱本明豊、石黒浩毅
  • Journal Title: 日本生物学的精神医学会誌 Vol.21. No.2 Pages: 97-104
  • NAID: 10029784830
• [Journal Article] アルコール依存の生物学 (2010)
  • Author(s): 菱本明豊
  • Journal Title: 日本生物学的精神医学会誌 Vol.21 No.1 Pages: 39-46
  • NAID: 10029784567
• [Journal Article] A putative cis-acting polymorphism in the NOS1 gene is associated with schizophrenia and NOS1 immunoreactivity in the postmortem brain. (2010)
  • Author(s): Cui H, et al
  • Journal Title: Schizophrenia Research Volume: 121(1-3) Pages: 172-178
  • Peer Reviewed
• [Journal Article] A common polymorphism in the 3'-UTR of the NOS1 gene was associated with completed suicides in Japanese male population. (2010)
  • Author(s): Cui H, et al
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry Volume: 34(6) Pages: 992-996
  • Peer Reviewed
• [Journal Article] Common genetic variations in TPH1/TPH2 genes are not associated with schizophrenia in Japanese population. (2010)
  • Author(s): Shiroiwa K, et al
  • Journal Title: Neurosci Lett Volume: 472(3) Pages: 194-198
  • Peer Reviewed
• [Journal Article] Alcohol and aldehyde dehydrogenase polymorphisms and risk for suicide ; A preliminary observation in the Japanese male population. (2010)
  • Author(s): Hishimoto A, et al
  • Journal Title: Genes Brain Behav Volume: 9(5) Pages: 498-502
  • Peer Reviewed
• [Journal Article] Association Study of RGS2 Gene Polymorphisms with Panic Disorder in Japanese. (2010)
  • Author(s): Mouri K, et al
  • Journal Title: Kobe Journal of Medical Sciences Volume: 55(5) Pages: 116-121
  • Peer Reviewed
• [Journal Article] 細胞接着因子と精神疾患 (2010)
  • Author(s): 菱本明豊, ら
  • Journal Title: 日本生物学的精神医学会誌 Volume: 21(2) Pages: 97-104
  • NAID: 10029784830
• [Journal Article] アルコール依存の生物学 (2010)
  • Author(s): 菱本明豊
  • Journal Title: 日本生物学的精神医学会誌 Volume: 21(1) Pages: 39-46
  • NAID: 10029784567
• [Journal Article] Common genetic variations in TPH1/ TPH2 genes are not associated with schizophrenia in Japanese population. (2010)
  • Author(s): Shiroiwa K, et al
  • Journal Title: Neurosci Lett Epub
  • Peer Reviewed
• [Journal Article] Alcohol and aldehyde dehydrogenase polymorphisms and risk for suicide ; A preliminary observation in the Japanese male population. (2010)
  • Author(s): Hishimoto A, et al
  • Journal Title: Genes Brain Behav Epub
  • Peer Reviewed
• [Journal Article] Association Study of RGS2 Gene Polymorphisms with Panic Disorder in Japanese. (2010)
  • Author(s): Mouri K, et al
  • Journal Title: Kobe Journal of Medical Sciences (in press)
  • Peer Reviewed
• [Journal Article] TPH2 is not a susceptibility gene for suicide in Japanese population. (2009)
  • Author(s): Mouri K, Hishimoto A(correspondent), Fukutake M, Shiroiwa K, Asano M, Nagasaki Y, Ueno Y, Shirakawa O, Nishiguchi N, Maeda K.
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry. 33(8) Pages: 1546-1550
  • Peer Reviewed
• [Journal Article] Species differences in cannabinoid receptor 2 (CNR2 gene): identification of novel human and rodent CB2 isoforms, differential tissue expression, and regulation by cannabinoid receptor ligands. (2009)
  • Author(s): Qing-Rong Liu, Chun-Hung Pan, Akitoyo Hishimoto, Chuan-Yun Li, Zheng-Xiong Xi, Alvaro Llorente-Berzal, Maria-Paz Viveros, Hiroki Ishiguro, Tadao Arinami, Emmanuel Shan Onaivi, George R.Uhl.
  • Journal Title: Genes, Brain and Behavior 8(5) Pages: 512-530
  • Peer Reviewed
• [Journal Article] 精神科外来における統合失調症患者に対するblonanserinの使用経験 (2009)
  • Author(s): 菱本明豊, 福武将映, 山本泰司, 他
  • Journal Title: 臨床精神薬理誌 Vol.12 No.9 Pages: 1999-2009
  • Peer Reviewed
• [Journal Article] 病歴の取り方 (2009)
  • Author(s): 菱本明豊
  • Journal Title: 精神科 Vol.15 No.1 Pages: 16-24
• [Journal Article] TPH2 is not a susceptibility gene for suicide in Japanese population. (2009)
  • Author(s): Mouri K, et al
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry 33(8) Pages: 1546-1550
  • Peer Reviewed
• [Journal Article] Species differences in cannabinoid receptor 2 (CNR2 gene): identification of novel human and rodent CB2 isoforms, differential tissue expression, and regulation by cannabinoid receptor ligands. (2009)
  • Author(s): Qing-Rong Liu, et al
  • Journal Title: Genes Brain Behav 8(5) Pages: 512-530
  • Peer Reviewed
• [Journal Article] 精神科外来における統合失調症患者に対するblonanserinの使用経験 (2009)
  • Author(s): 菱本明豊
  • Journal Title: 臨床精神薬理誌 12(9) Pages: 1999-2009
  • Peer Reviewed
• [Journal Article] 病歴の取り方 (2009)
  • Author(s): 菱本明豊
  • Journal Title: 精神科 15(1) Pages: 16-24
• [Presentation] Association of FKBP5 gene haplotypes with completed suicide in Japanese population (2011)
  • Author(s): Akitoyo Hishimoto, Toru Sasada, Masaaki Fukutake, Kyoichi Shiroiwa, Irwan Suoriyanto, Osamu Shirakawa
  • Organizer: 19th European Congress Psychiatry-EPA2011
  • Place of Presentation: Austria
• [Presentation] 自殺とBDNF遺伝子多型との相関研究 (2010)
  • Author(s): 吉田正邦, ら
  • Organizer: 第32回日本生物学的精神医学会
  • Place of Presentation: リーガロイヤルホテル小倉(福岡県)
  • Year and Date: 2010-10-10
• [Presentation] アルコール依存症と自殺-遺伝疫学的視点から- (2010)
  • Author(s): 菱本明豊
  • Organizer: アルコール薬物依存関連合同学術総会(第45回日本アルコール・薬物医学会)
  • Place of Presentation: リーガロイヤルホテル小倉(福岡県)
  • Year and Date: 2010-10-08
• [Presentation] 神経型一酸化窒素合成酵素(NOS1)遺伝子のシス活性を持つ一塩基多型は死後脳NOS1免疫反応レベルと統合失調症に相関する (2010)
  • Author(s): 菱本明豊, ら
  • Organizer: 第32回日本生物学的精神医学会
  • Place of Presentation: リーガロイヤルホテル小倉(福岡県)
  • Year and Date: 2010-10-08
• [Presentation] A putative cis-acting polymorphism in the NOS1 gene is associated with schizophrenia and NOS1 immunoreactivity in the postmortem brain (2010)
  • Author(s): Hishimoto A
  • Organizer: Taiwanese Society of Biological Psychiatry and Neuropsychopharmacology 2010 Fall Meeting
  • Place of Presentation: Taipei(Taiwan)(招待講演)
  • Year and Date: 2010-09-18
• [Presentation] 抗酒薬のレビュー:治療メカニズム、治療エビデンス、副作用など (2010)
  • Author(s): 菱本明豊
  • Organizer: 第32回日本アルコール関連問題学会
  • Place of Presentation: 神戸国際会議場(兵庫県)
  • Year and Date: 2010-07-16
• [Presentation] Alcohol and aldehyde dehydrogenase polymorphisms and risk for suicide (2010)
  • Author(s): Hishimoto A, et al
  • Organizer: the 18th European Congress of Psychiatry
  • Place of Presentation: Munich (Germany)
  • Year and Date: 2010-02-28
• [Presentation] A putative cis-acting polymorphism in the NOS1 gene is associated with schizophrenia and NOS1 immuno-reactivity in the postmortem brain (2010)
  • Author(s): Akitoyo Hishimoto
  • Organizer: Taiwanese Society of Biological Psychiatry and Neuropsychopharmacology 2010 Fall Meeting
  • Place of Presentation: Taiwan
• [Presentation] Alcohol and aldehyde dehydrogenase polymorphisms and risk for suicide. (2010)
  • Author(s): Akitoyo Hishimoto, Kentaro Mouri, Osamu Shirakawa
  • Organizer: 18th European Congress Psychiatry-EPA 2011
  • Place of Presentation: Germany
• [Presentation] A genetic variation of NOS1is associated with schizophrenia and NOS1 expression in the brain (2010)
  • Author(s): Akitoyo Hishimoto, Cui huxing, Naoki Nishiguchi, Masaya Yanagi, Akitoyo Hishimoto, Kentaro Mouri, Noboru Kitamjura, Kenji Hashimoto, Osamu Shirakawa
  • Organizer: 第32回日本生物学的精神医学会
  • Place of Presentation: 福岡
• [Presentation] 自殺とBDNF遺伝子多型との相関研究 (2010)
  • Author(s): 吉田正邦、白岩恭一、イルワンスプリヤント、江口典臣、福武将映、笹田徹、菱本明豊
  • Organizer: 第32回日本生物学的精神医学会
  • Place of Presentation: 福岡
• [Presentation] 精神科外来における統合失調症患者に対するblonanserinの使用経験 (2009)
  • Author(s): 福武将映, ら
  • Organizer: 第19回日本臨床精神神経薬理学会
  • Place of Presentation: 国立京都国際会館(京都府)
  • Year and Date: 2009-11-13
• [Presentation] Neurobiology of suicide (2009)
  • Author(s): Maeda K, et al
  • Organizer: The Kobe Conference of Neuropsychiatric Association
  • Place of Presentation: 神戸国際会議場(兵庫県)
  • Year and Date: 2009-09-12
• [Presentation] RGS2遺伝子多型とパニック障害との相関研究 (2009)
  • Author(s): 毛利健太朗, ら
  • Organizer: 第31回日本生物学的精神医学会
  • Place of Presentation: 国立京都国際会館(京都府)
  • Year and Date: 2009-04-25
• [Book] 脳(ブレイン)バンク 精神疾患の謎を解くために (2011)
  • Author(s): 加藤忠史, ブレインバンク委員会
  • Publisher: 光文社新書
• [Book] 専門医のための精神科臨床リュミエール29(張賢徳編)(自殺予防の基本戦略)(「自殺の生物学的知見」) (2011)
  • Author(s): 福武将映、菱本明豊、白川治
  • Publisher: 中山書店
• [Book] 自殺の生物学(松本英夫、傳田健三編)(子どもの心の診療シリーズ、4巻、子どもの不安障害と抑うつ) (2010)
  • Author(s): 菱本明豊, 辻井農亜, 白川治
  • Publisher: 中山書店
• [Book] 子どもの心の診療シリーズ、4巻、子どもの不安障害と抑うつ(松本英夫、傳田健三 編)(自殺の生物学) (2010)
  • Author(s): 菱本明豊, ら
  • Total Pages: 296
  • Publisher: 中山書店
• [Book] ブロナンセリン100の症例「統合失調症の再発再燃例へのブロナンセリンの効果」 (2009)
  • Author(s): 菱本明豊
  • Publisher: 星和書店
• [Book] ブロナンセリン100の症例(統合失調症の再発再燃例へのブロナンセリンの効果) (2009)
  • Author(s): 菱本明豊, ら
  • Total Pages: 317
  • Publisher: 星和書店
• [Remarks] 生物学的精神医学会ブレインバンク委員会委員として一般書『脳(ブレイン)バンク 精神疾患の謎を解くために,加藤忠史&ブレインバンク委員会 光文社新書,2011』を執筆担当し、精神医学研究の啓蒙を行った。