Functional analysis of suicide-related genes in brain

• Project/Area Number: 26461718
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Kobe University
• Principal Investigator: Hishimoto Akitoyo 神戸大学, 医学研究科, 准教授 (50529526)
• Co-Investigator(Kenkyū-buntansha): 曽良 一郎 神戸大学, 医学研究科, 教授 (40322713) ; 泉 剛 北海道大学, 医学研究科, 准教授 (60312360)
• Co-Investigator(Renkei-kenkyūsha): Watanabe Masahiko 北海道大学, 医学研究科, 教授 (70210945)
• Research Collaborator: Kusumi Ichiro 北海道大学, 医学研究科, 教授 (30250426)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 自殺 / GWAS / 動物モデル / 神経幹細胞 / 自殺の生物学 / ゲノムワイド関連研究 / 神経前駆細胞 / SNP / うつ病

Outline of Final Research Achievements

The genetic research of complete suicide is behind other mental problems because it is extremely difficult to obtain tissue samples of completed suicide. Under the difficult situation, we performed a GWAS using 500 samples of suicide completers, and found two candidates of suicide-related gene; PTCHD3 and RAB18.
Here, we investigated the function of these candidate genes in chronic stressed rats and mouse neural stem cells. Stressed rats showed higher PTCHD3 expression in prefrontal cortex and hippocampus, and lower RAB18 expression in amygdala. In mouse neural stem cells with RAB18 knockdown, cell proliferation and survival were significantly increased compared to controls. Our results suggest aberrant expression of these suicide-related genes may be associated with brain abnormalities in stress conditons. Replication GWAS of suicide completers and further in vivo and in vitro analyses are needed in future studies.

Research Products

• [Journal Article] Association study of MIF promoter polymorphisms with suicide completers in the Japanese population (2017)
  • Author(s): Naofumi Shimmyo, Akitoyo Hishimoto, Ikuo Otsuka, Satoshi Okazaki, Shuken Boku, Kentaro Mouri, Tadasu Horai, Motonori Takahashi, Yasuhiro Ueno, Osamu Shirakawa, Ichiro Sora
  • Journal Title: Neuropsychiatric Disease and Treatment Volume: 13 Pages: 899-908
  • DOI: 10.2147/ndt.s130855
  • NAID: 120006024452
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Aberrant telomere length and mitochondrial DNA copy number in suicide completers (2017)
  • Author(s): Ikuo Otsuka, Takeshi Izumi, Shuken Boku, Atsushi Kimura, Yuan Zhang, Kentaro Mouri, Satoshi Okazaki, Kyoichi Shiroiwa, Motonori Takahashi, Yasuhiro Ueno, Osamu Shirakawa, Ichiro Sora, Akitoyo Hishimoto
  • Journal Title: Scientific Reports Volume: in press
  • NAID: 120006373780
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 自殺既遂の生物学的研究 (2016)
  • Author(s): 大塚郁夫、曽良一郎、菱本明豊
  • Journal Title: 日本神経精神薬理学雑誌 Volume: 36 Pages: 55-62
  • Peer Reviewed
• [Journal Article] Slow synaptic transmission mediated by TRPV1 channels in CA3 interneurons of the hippocampus. (2016)
  • Author(s): Eguchi N, Hishimoto A, Sora I, Mori M.
  • Journal Title: Neurosci Lett. Volume: 616 Pages: 170-176
  • DOI: 10.1016/j.neulet.2015.12.065
  • Peer Reviewed
• [Journal Article] Rare truncating variations and risk of schizophrenia: Whole-exome sequencing in three families with affected siblings and a three-stage follow-up study in a Japanese population. (2016)
  • Author(s): Watanabe Y, Nunokawa A, Shibuya M, Ikeda M, Hishimoto A, Kondo K, Egawa J, Kaneko N, Muratake T, Saito T, Okazaki S, Shimasaki A, Igeta H, Inoue E, Hoya S, Sugai T, Sora I, Iwata N, Someya T
  • Journal Title: Psychiatry Research Volume: 235 Pages: 13-18
  • DOI: 10.1016/j.psychres.2015.12.011
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The serum level of NX-DCP-R, but not DCP, is not increased in alcoholic liver disease without hepatocellular carcinoma. (2016)
  • Author(s): Saito M, Yano Y, Hirano H, Momose K, Mouri K, Hishimoto A, Yoshida M, Azuma T.
  • Journal Title: Cancer Biomark. Volume: 16 Issue: 1 Pages: 171-180
  • DOI: 10.3233/cbm-150553
  • Peer Reviewed
• [Journal Article] Molecular Histochemistry Identifies Peptidomic Organization and Reorganization Along Striatal Projection Units. (2016)
  • Author(s): Hishimoto A, Nomaru H, Ye K, Nishi A, Lim J, Aguilan JT, Nieves E, Kang G, Angeletti RH, Hiroi N.
  • Journal Title: Biol Psychiatry. Volume: 79 Issue: 5 Pages: 415-420
  • DOI: 10.1016/j.biopsych.2015.09.012
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] 自殺既遂の生物学的研究 (2016)
  • Author(s): 大塚郁夫、菱本明豊
  • Journal Title: 日本神経精神薬理学雑誌 Volume: 36 Pages: 0-0
  • Peer Reviewed
• [Journal Article] A decrease in protein level and a missense polymorphism of KIF17 are associated with schizophrenia. (2015)
  • Author(s): Ratta-Apha W, Mouri K, Boku S, Ishiguro H, Okazaki S, Otsuka I, Sora I, Arinami T, Shirakawa O, Hishimoto A.
  • Journal Title: Psychiatry Res. Volume: 230 Issue: 2 Pages: 424-429
  • DOI: 10.1016/j.psychres.2015.09.031
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Lack of cardinal symptoms of meningitis in a hospitalized patient with chronic schizophrenia: lessons to be learned. (2015)
  • Author(s): So R, Hirota T, Yamamoto Y, Hishimoto A, Correll CU.
  • Journal Title: Gen Hosp Psychiatry. Volume: 37 Issue: 6 Pages: 621-621
  • DOI: 10.1016/j.genhosppsych.2015.07.011
  • Peer Reviewed
• [Journal Article] Association analysis of the HLA-DRB1*01 and HLA-DRB1*04 with schizophrenia by tag SNP genotyping in the Japanese population. (2015)
  • Author(s): Ratta-apha W, Boku S, Mouri K, Okazaki S, Otsuka I, Watanabe Y, Nunokawa A, Someya T, Shirakawa O, Sora I, Hishimoto A.
  • Journal Title: Psychiatry Res. Volume: 229 Issue: 1-2 Pages: 627-628
  • DOI: 10.1016/j.psychres.2015.07.016
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Assessment of copy number variations in the brain genome of schizophrenia patients. (2015)
  • Author(s): Sakai M, Watanabe Y, Someya T, Araki K, Shibuya M, Niizato K, Oshima K, Kunii Y, Yabe H, Matsumoto J, Wada A, Hino M, Hashimoto T, Hishimoto A, Kitamura N, Iritani S, Shirakawa O, Maeda K, Miyashita A, Niwa S, Takahashi H, Kakita A, Kuwano R, Nawa H.
  • Journal Title: Mol Cytogenet. Volume: 8 Issue: 1 Pages: 46-46
  • DOI: 10.1186/s13039-015-0144-5
  • Peer Reviewed / Open Access
• [Journal Article] Association analysis of the Cadherin13 gene with schizophrenia in the Japanese population. (2015)
  • Author(s): Otsuka I, Watanabe Y, Hishimoto A, Boku S, Mouri K, Shiroiwa K, Okazaki S, Nunokawa A, Shirakawa O, Someya T, Sora I.
  • Journal Title: Neuropsychiatr Dis Treat. Volume: 11 Pages: 1381-1393
  • DOI: 10.2147/ndt.s84736
  • NAID: 120005657654
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Blood Diagnostic Biomarkers for Major Depressive Disorder using Multiplex DNA Methylation Profiles: Discovery and Validation. (2015)
  • Author(s): Shusuke Numata, Kazuo Ishii, Atsushi Tajima, Jun-Ichi Iga, Makoto Kinoshita, Shinya Watanabe, Hidehiro Umehara, Manabu Fuchikami, Satoshi Okada, Shuken Boku, Akitoyo Hishimoto, Shinji Shimodera, Issei Imoto, Shigeru Morinobu, Tetsuro Ohmori
  • Journal Title: Epigenetics Volume: 10(2) Issue: 2 Pages: 135-141
  • DOI: 10.1080/15592294.2014.1003743
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A rare MIR138-2 gene variation is associated with schizophrenia in a Japanese population (2014)
  • Author(s): Watanabe, Y., Hishimoto, A., Shibuya, M., Nunokawa, A., Kaneko, N., Igeta, Egawa, J., Mouri, K., Sora, I., Someya, T.
  • Journal Title: Psychiatry Research Volume: 215 Issue: 3 Pages: 801-802
  • DOI: 10.1016/j.psychres.2013.12.029
  • Peer Reviewed
• [Journal Article] Association analysis of putative cis-acting polymorphisms of interleukin-19 gene with schizophrenia (2014)
  • Author(s): Okazaki, S., Watanabe, Y., Hishimoto, A., Sasada, T., Mouri, K., Shiroiwa, K., Eguchi, N., Ratta-Apha, W., Otsuka, I., Nunokawa, A., Kaneko, N., Shibnuya. M., Someya, T., Shirakawa, O., Sora, I.
  • Journal Title: Progress in Neuro-Psychopharmacology & Biological Psychiatry Volume: 50 Pages: 151-156
  • DOI: 10.1016/j.pnpbp.2013.12.006
  • Peer Reviewed
• [Journal Article] Haplotype analysis of the DISC1 Ser704Cys variant in Japanese suicide completers. (2014)
  • Author(s): Ratta-Apha W, Hishimoto A, Mouri K, Shiroiwa K, Sasada T, Yoshida M, Okazaki S, Supriyanto I, Asano M, Ueno Y, Shirakawa O, Sora I
  • Journal Title: Psychiatry Res Volume: 215 Issue: 1 Pages: 249-251
  • DOI: 10.1016/j.psychres.2013.11.007
  • Peer Reviewed
• [Journal Article] 慢性疼痛に対しデュロキセチンが奏功した4症例の検討 (2014)
  • Author(s): 大塚郁夫, 白岩恭一, 毛利健太郎, 菱本 明豊，曽良一郎
  • Journal Title: 臨床精神薬理 Volume: 17 Pages: 1151-1156
  • Peer Reviewed
• [Journal Article] SSRI/SNRI投与後に賦活症状によるものと考えられる自殺念慮・自殺行動が出現した5症例の検討 (2014)
  • Author(s): 笹田 徹, 田中 究, 菱本 明豊
  • Journal Title: 臨床精神薬理 Volume: 17 Pages: 245-252
  • Peer Reviewed
• [Book] Depression Frontier 2 うつ病臨床のこんな疑問に答える -脳科学からのアプローチ- (2016)
  • Author(s): 大塚郁夫、菱本明豊
  • Total Pages: 138
  • Publisher: 医薬ジャーナル社