Analysis of molecular pathophysiology of gender identity disorder using microarray method

• Project/Area Number: 15K09806
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Okayama University
• Principal Investigator: Okahisa Yuko 岡山大学, 大学病院, 助教 (90583097)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2015: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
• Keywords: 性同一性障害 / 臨床精神分子遺伝学

Outline of Final Research Achievements

The purpose of this study is to reveal the molecular pathophysiology of gender identity disorder. We conducted whole-genome analysis of 206 female-to-male trans-sexual individuals and 1557 control subjects using Japonica array but failed to identify pathogenesis of gender identity disorder. We intend to perform further research using larger samples.

Academic Significance and Societal Importance of the Research Achievements

病態の手掛かりがない性同一性障害について全ゲノム解析を行ったことは、病態解明に向けた有意義な取り組みであったと考える。今回の解析では病態の解明につながる結果は得られなかったが、この研究を手掛かりにより多くのサンプルでの全ゲノム解析やメタボローム解析を行い、病態解明につなげたい。

Research Products

• [Journal Article] Rare loss of function mutations in N-methyl-d-aspartate glutamate receptors and their contributions to schizophrenia susceptibility (2018)
  • Author(s): Yu Yanjie、Lin Yingni、Takasaki Yuto、Wang Chenyao、Kimura Hiroki、Xing Jingrui、Ishizuka Kanako、Toyama Miho、Kushima Itaru、Mori Daisuke、Arioka Yuko、Uno Yota、Shiino Tomoko、Nakamura Yukako、Okada Takashi、Morikawa Mako、Ikeda Masashi、Iwata Nakao、Okahisa Yuko、Takaki Manabu、Sakamoto Shinji、et al.
  • Journal Title: Translational Psychiatry Volume: 8 Issue: 1 Pages: 12-20
  • DOI: 10.1038/s41398-017-0061-y
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Effects of the antipsychotics haloperidol, clozapine, and aripiprazole on the dendritic spine. (2018)
  • Author(s): Takaki M, Kodama M, Mizuki Y, Kawai H, Yoshimura B, Kishimoto M, Sakamoto S, Okahisa Y, Yamada N.
  • Journal Title: Eur Neuropsychopharmacol. Volume: 28(5) Issue: 5 Pages: 610-619
  • DOI: 10.1016/j.euroneuro.2018.03.004
  • Peer Reviewed / Open Access
• [Journal Article] Assessment of a glyoxalase I frameshift variant, p.P122fs, in Japanese patients with schizophrenia. (2018)
  • Author(s): Ishizuka K, Kimura H, Kushima I, Inada T, Okahisa Y, Ikeda M, Iwata N, Mori D, Aleksic B, Ozaki N.
  • Journal Title: Psychiatr Genet. Volume: 5 Issue: 5 Pages: 90-93
  • DOI: 10.1097/ypg.0000000000000204
  • Peer Reviewed / Open Access
• [Journal Article] Genome-Wide Association Study Detected Novel Susceptibility Genes for Schizophrenia and Shared Trans-Populations/Diseases Genetic Effect (2018)
  • Author(s): Ikeda M,Takahashi A,Kamatani Y,Momozawa Y,Saito T,Kondo K,Shimasaki A,Kawase K,Sakusabe T,Iwayama Y,Toyota T,Wakuda T,Kikuchi M,Kanahara N,Yamamori H,Yasuda Y,Watanabe Y,Hoya S,Aleksic B,Kushima I,Arai H,Takaki M,Hattori K,Kunugi H,Okahisa Y,Ohnuma T,Ozaki N,Someya T,Hashimoto R,Yoshikawa T,Kubo M,Iwata N
  • Journal Title: Schizophrenia Bulletin Volume: 印刷中 Issue: 4 Pages: 824-834
  • DOI: 10.1093/schbul/sby140
  • Peer Reviewed / Open Access
• [Journal Article] A genome-wide association study identifies two novel susceptibility loci and trans population polygenicity associated with bipolar disorder. (2017)
  • Author(s): Ikeda M, Shimasaki A, Takahashi A,et al.
  • Journal Title: Mol Psychiatry Volume: in press Issue: 3 Pages: 1-9
  • DOI: 10.1038/mp.2016.259
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Rare genetic variants in CX3CR1 and their contribution to the increased risk of schizophrenia and autism spectrum disorders (2017)
  • Author(s): Ishizuka K、Fujita Y、Kawabata T、Kimura H、Iwayama Y、Inada T、Okahisa Y、Egawa J、Usami M、Kushima I、Uno Y、Okada T、Ikeda M、Aleksic B、Mori D、Someya To、Yoshikawa T、Iwata N、Nakamura H、Yamashita T、Ozaki N
  • Journal Title: Translational Psychiatry Volume: 7 Issue: 8 Pages: e1184-e1184
  • DOI: 10.1038/tp.2017.173
  • Peer Reviewed / Open Access
• [Journal Article] A novel rare variant R292H in RTN4R affects growth cone formation and possibly contributes to schizophrenia susceptibility (2017)
  • Author(s): Kimura H、Fujita Y、Kawabata T、Ishizuka K、Wang C、Iwayama Y、Okahisa Y、Kushima I、Morikawa M、Uno Y、Okada T、Ikeda M、Inada T、Branko A、Mori D、Yoshikawa T、Iwata N、Nakamura H、Yamashita T、Ozaki N
  • Journal Title: Translational Psychiatry Volume: 7 Issue: 8 Pages: e1214-e1214
  • DOI: 10.1038/tp.2017.170
  • Peer Reviewed / Open Access
• [Journal Article] Human Rho Guanine Nucleotide Exchange Factor 11 (ARHGEF11) Regulates Dendritic Morphogenesis (2017)
  • Author(s): Mizuki Y, Takaki M, Sakamoto S, Okamoto S, Kishimoto M, Okahisa Y, Itoh M, Yamada N
  • Journal Title: Int J Mol Sci Volume: 18(1) Issue: 1 Pages: 1-11
  • DOI: 10.3390/ijms18010067
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Estimated cognitive decline in patients with schizophrenia: A multicenter study. (2017)
  • Author(s): Fujino H, Sumiyoshi C, Yasuda Y, Yamamori H, Fujimoto M, Fukunaga M, Miura K, Takebayashi Y, Okada N, Isomura S, Kawano N, Toyomaki A, Kuga H, Isobe M, Oya K, Okahisa Y, Takaki M, Hashimoto N, Kato M, Onitsuka T, Ueno T, Ohnuma T, Kasai K, Ozaki N, Sumiyoshi T, Imura O, Hashimoto R
  • Journal Title: sychiatry Clin Neurosci. Volume: 印刷中 Issue: 5 Pages: 294-300
  • DOI: 10.1111/pcn.12474
  • Peer Reviewed / Open Access
• [Journal Article] Individual risk alleles of susceptibility to schizophrenia are associated with poor clinical and social outcomes. (2016)
  • Author(s): Sakamoto S, Takaki M, Okahisa Y, Mizuki Y, Inagaki M, Ujike H, Mitsuhashi T, Takao S, Ikeda M, Uchitomi Y, Iwata N, Yamada N.
  • Journal Title: J Hum Genet. Volume: 61 Issue: 4 Pages: 329-334
  • DOI: 10.1038/jhg.2015.153
  • NAID: 40020802866
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The Relationship Between Development of Neuronal and Astrocytic Tau Pathologies in Subcortical Nuclei and Progression of Argyrophilic Grain Disease (2016)
  • Author(s): Chikako Ikeda, Osamu Yokota, Shigeto Nagao, Hideki Ishizu, Etsuko Oshima, Masato Hasegawa, Yuko Okahisa, Seishi Terada, Norihito Yamada
  • Journal Title: Brain Pathology Volume: 印刷中 Issue: 4 Pages: 488-505
  • DOI: 10.1111/bpa.12319
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A genome-wide association study of late-onset Alzheimer's disease in a Japanese population. (2015)
  • Author(s): Hirano A, Ohara T, Takahashi A, Aoki M, Fuyuno Y, Ashikawa K, Morihara T, Takeda M, Kamino K, Oshima E, Okahisa Y, Shibata N, Arai H, Akatsu H, Ikeda M, Iwata N, Ninomiya T, Monji A, Kitazono T, Kiyohara Y, Kubo M, Kanba S.
  • Journal Title: Psychiatr Genet. Volume: 25（4） Issue: 4 Pages: 139-146
  • DOI: 10.1097/ypg.0000000000000090
  • Peer Reviewed
• [Journal Article] Difference in determinants of caregiver burden between amnestic mild cognitive impairment and mild Alzheimer's disease. (2015)
  • Author(s): Ikeda C, Terada S, Oshima E, Hayashi S, Okahisa Y, Takaki M, Inagaki M, Yokota O, Uchitomi Y.
  • Journal Title: Psychiatry Res. Volume: 226（1） Issue: 1 Pages: 242-246
  • DOI: 10.1016/j.psychres.2014.12.055
  • Peer Reviewed / Open Access
• [Journal Article] Factors predicting work outcome in Japanese patients with schizophrenia: role of multiple functioning levels (2015)
  • Author(s): Sumiyoshi C, Harvey PD, Takaki M, Okahisa Y, Sato T, Sora I, Nuechterlein KH, Subotnik KL, Sumiyoshi T.
  • Journal Title: Schizophrenia Res: Cognition Volume: 2 Pages: 105-112
  • Peer Reviewed / Int'l Joint Research
• [Presentation] The relationship of N-methyl-D-aspartate receptor antibody and psychiatric disorders (2018)
  • Author(s): Kawai H, Sakamoto S, Kishimoto M, Okahisa Y, Takaki M, Yamada N
  • Organizer: CINP 31st World Congress
  • Int'l Joint Research
• [Presentation] Effects of the antipsychotics haloperidol, clozapine, and aripiprazole on the dendritic spine (2018)
  • Author(s): Takaki M, Kodama M, Mizuki Y, Kawai H, Yoshimura B, Kishimoto M, Sakamoto S, Okahisa Y, Yamada N.
  • Organizer: CINP 31st World Congress
  • Int'l Joint Research
• [Presentation] 電気痙攣療法における発作の質に麻酔薬が与える影響の検討 (2016)
  • Author(s): 酒本真次, 藤原雅樹, 岸本真希子, 岡久祐子, 髙木学, 山田了士
  • Organizer: 第26回 日本臨床精神神経薬理学会
  • Place of Presentation: 大分
  • Year and Date: 2016-11-17
• [Presentation] 統合失調症患者において、アリピプラゾールへの切り替え方法が継続率に与える影響の検討 (2016)
  • Author(s): 大林芳明, 吉村文太, 酒本真次, 岸本真希子, 岡久祐子, 武田俊彦, 髙木学, 山田了士
  • Organizer: 第26回 日本臨床精神神経薬理学会
  • Place of Presentation: 大分
  • Year and Date: 2016-11-17
• [Presentation] 日中の仮眠と易怒性が初期症状であり早期診断が困難であった神経梅毒の一例 (2016)
  • Author(s): 寒川尚登, 岸本真希子, 岡久祐子, 大島悦子, 川田清宏, 山田了士, 田所功, 幡中典子, 太田康之, 阿部康二
  • Organizer: 第57回 中国・四国精神神経学会
  • Place of Presentation: 松山
  • Year and Date: 2016-11-10
• [Presentation] Expression Profiles and Neurocognitive/Social Functions as a Predictive Biomarker of Schizophrenia (2016)
  • Author(s): Okahisa Y, Sakamoto S, Kishimoto M, Takaki M, Yamada N.
  • Organizer: 10th International Conference on Early Psychosis
  • Place of Presentation: Milan, Italy
  • Year and Date: 2016-10-19
  • Int'l Joint Research
• [Presentation] PDE4B 遺伝子が統合失調症の発症脆弱性と認知機能に与える影響 (2016)
  • Author(s): 酒本真次, 高木学, 岡本宗次郎, 岸本真希子, 岡久祐子, 大井一高, 橋本亮太, 山田了士
  • Organizer: 第38回 日本生物学的精神医学会
  • Place of Presentation: 福岡
  • Year and Date: 2016-09-08
• [Presentation] 抗NMDA受容体抗体が神経発達に及ぼす影響の検討 (2016)
  • Author(s): 岡本宗次郎, 酒本真次, 岸本真希子, 岡久祐子, 髙木学, 山田了士
  • Organizer: 第38回 日本生物学的精神医学会
  • Place of Presentation: 福岡
  • Year and Date: 2016-09-08
• [Presentation] Factors to predict work outcome in Japanese patients with schizophrenia: cutoff performances on measures of functional outcomes (2016)
  • Author(s): Sumiyoshi C, Takaki M, Okahisa Y, Sato T, Sora I, Harvey P.D, Nuechterlein K.H, Subotnik K.L, Sumiyoshi T.
  • Organizer: 5th Biennial Schizophrenia International Research Society Conference
  • Place of Presentation: Florence, Italy
  • Year and Date: 2016-04-02
  • Int'l Joint Research
• [Presentation] Expression profiles and social function as a predictive biomarker of schizophrenia : a pilot study (2016)
  • Author(s): Okahisa Y, Sakamoto S, Takaki M, Yamada N.
  • Organizer: 5th Biennial Schizophrenia International Research Society Conference
  • Place of Presentation: Florence, Italy
  • Int'l Joint Research
• [Presentation] Clozapineによる無顆粒球症の改善後に薬剤性過敏性症候群（DIHS）を来した一例 (2015)
  • Author(s): 原紘志、岡久祐子、酒本真次、川田清宏、高木学、山田了士
  • Organizer: 第56回中国・四国精神神経学会
  • Place of Presentation: 倉敷
  • Year and Date: 2015-11-13
• [Presentation] 統合失調症患者の認知機能障害に対するクロザピンの有効性の検討 (2015)
  • Author(s): 酒本真次、水木寛、岡久祐子、高木学、山田了士
  • Organizer: 第25回日本臨床精神神経薬理学会
  • Place of Presentation: 東京
  • Year and Date: 2015-10-29
• [Presentation] Expression profiles and cognitive function as a predictive biomarker of schizophrenia : a pilot study (2015)
  • Author(s): Okahisa Y, Sakamoto S, Takaki M, Yamada N.
  • Organizer: XXIIIRD World Congress of Psychiatric Genetics
  • Place of Presentation: Toronto, Canada
  • Year and Date: 2015-10-18
  • Int'l Joint Research
• [Presentation] NMDA受容体機能関連遺伝子と統合失調症患者の臨床的・社会的転帰との関連研究 (2015)
  • Author(s): 酒本真次、高木学、岡久祐子、水木寛、山田了士
  • Organizer: 第37回日本生物学的精神医学会 第45回日本神経精神薬理学会 合同年会
  • Place of Presentation: 東京
  • Year and Date: 2015-09-25