Identification of the effect of copy number variations associated with schizophrenia on brain networks

• Project/Area Number: 17K10295
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Nagoya University
• Principal Investigator: Yamamoto Maeri 名古屋大学, 医学部附属病院, 助教 (50778272)
• Project Period (FY): 2017-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 統合失調症 / ゲノムコピー数変異 / MRI / functional MRI / ゲノムコピー変異 / Voxel-based-morphometry / voxel-based-morphometry / functional connectivity / ゲノム

Outline of Final Research Achievements

Clinical phenotypic information was examined retrospectively for four patients with 3q29 deletions identified using the array CGH method. All patients had treatment-resistant features, and clozapine, a treatment for treatment-resistant schizophrenia, was used in two patients and was effective in both cases.
The resting-state functional MRI analysis revealed the aberrant functional connectivity between the thalamus and visual cortex is related to attentional impairment in schizophrenia.

Academic Significance and Societal Importance of the Research Achievements

本研究は、3q29欠失を持つ統合失調症患者を対象とした神経生物学的研究によって治療抵抗性統合失調症のメカニズム解明と治療薬開発に繋がる可能性を示した。一方、統合失調症における機能的脳内ネットワークの障害と注意障害との関係を明らかにした。今後3q29欠失を持つ統合失調症患者を対象に解析を行うことで3q29欠失が脳内ネットワークおよび認知機能に与える影響を検討することができる。

Research Products

• [Journal Article] Treatment‐resistant schizophrenia in patients with 3q29 deletion: A case series of four patients (2022)
  • Author(s): Nawa Yoshihiro、Kushima Itaru、Aleksic Branko、Yamamoto Maeri、Kimura Hiroyuki、Banno Masahiro、Hashimoto Ryota、Ozaki Norio
  • Journal Title: Psychiatry and Clinical Neurosciences Volume: - Issue: 7 Pages: 338-339
  • DOI: 10.1111/pcn.13361
  • Peer Reviewed / Open Access
• [Journal Article] Support vector machine-based classification of schizophrenia patients and healthy controls using structural magnetic resonance imaging from two independent sites (2020)
  • Author(s): Yamamoto Maeri、Bagarinao Epifanio、Kushima Itaru、Takahashi Tsutomu、Sasabayashi Daiki、Inada Toshiya、Suzuki Michio、Iidaka Tetsuya、Ozaki Norio
  • Journal Title: PLOS ONE Volume: 15 Issue: 11 Pages: 0239615-0239615
  • DOI: 10.1371/journal.pone.0239615
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Quantitative facial expression analysis revealed the efficacy and time course of oxytocin in autism (2019)
  • Author(s): Owada Keiho、（他28名22番目）Yamamoto Maeri
  • Journal Title: Brain Volume: 142 Issue: 7 Pages: 2127-2136
  • DOI: 10.1093/brain/awz126
  • Peer Reviewed / Open Access
• [Journal Article] Application of eye trackers for understanding mental disorders: Cases for schizophrenia and autism spectrum disorder (2019)
  • Author(s): Shishido Emiko、Ogawa Shiori、Miyata Seiko、Yamamoto Maeri、Inada Toshiya、Ozaki Norio
  • Journal Title: Neuropsychopharmacology Reports Volume: 39 Issue: 2 Pages: 72-77
  • DOI: 10.1002/npr2.12046
  • Peer Reviewed / Open Access
• [Journal Article] White matter microstructural alterations across four major psychiatric disorders: mega-analysis study in 2937 individuals (2019)
  • Author(s): Koshiyama Daisuke、(他38名18番目）Yamamoto Meeri
  • Journal Title: Molecular Psychiatry Volume: 25 Issue: 4 Pages: 883-895
  • DOI: 10.1038/s41380-019-0553-7
  • NAID: 120006980539
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Aberrant functional connectivity between the thalamus and visual cortex is related to attentional impairment in schizophrenia (2018)
  • Author(s): Yamamoto Maeri、Kushima Itaru、Suzuki Ryohei、Branko Aleksic、Kawano Naoko、Inada Toshiya、Iidaka Tetsuya、Ozaki Norio
  • Journal Title: Psychiatry Research: Neuroimaging Volume: 278 Pages: 35-41
  • DOI: 10.1016/j.pscychresns.2018.06.007
  • Peer Reviewed / Open Access
• [Journal Article] Genetic and animal model analyses reveal the pathogenic role of a novel deletion of RELN in schizophrenia. (2018)
  • Author(s): Sobue A, Kushima I, Nagai T, Shan W, Kohno T, Aleksic B, Aoyama Y, Mori D, Arioka Y, Kawano N, Yamamoto M, Hattori M, Nabeshima T, Yamada K, Ozaki N.
  • Journal Title: Sci Rep. Volume: 8 Issue: 1 Pages: 13046-13046
  • DOI: 10.1038/s41598-018-31390-w
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Comparative Analyses of Copy-Number Variation in Autism Spectrum Disorder and Schizophrenia Reveal Etiological Overlap and Biological Insights. (2018)
  • Author(s): Kushima I, (27名中略）, Hashimoto R,(80名中29番目) , et al.
  • Journal Title: Cell Rep Volume: 24(11) Issue: 11 Pages: 2838-2856
  • DOI: 10.1016/j.celrep.2018.08.022
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] High-resolution copy number variation analysis of schizophrenia in Japan. (2017)
  • Author(s): Kushima I, Aleksic B, Nakatochi M, Shimamura T, Shiino T, Yoshimi A, Kimura H, Takasaki Y, Wang C, Xing J, Ishizuka K, Oya-Ito T, Nakamura Y, Arioka Y, Maeda T, Yamamoto M, Yoshida M, Noma H, Hamada S, Morikawa M, Uno Y, Okada T, Iidaka T, Iritani S, Yamamoto T,
  • Journal Title: Molecular Psychiatry Volume: 22 Issue: 3 Pages: 430-440
  • DOI: 10.1038/mp.2016.88
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] 多施設共同研究による統合失調症と双極性障害の大脳皮質構造画像解析 (2022)
  • Author(s): 松本 純弥、福永 雅喜、三浦 健一郎、岡田 直大、 根本 清貴、藤本 美智子、 肥田 道彦、 宮田 淳、 大井 一高、 中瀧 理仁、吉村 玲児、岡本 泰昌、原田 健一郎、橋本 直樹、鬼塚 俊明、 山本 真江里、 山末 英典、高橋 努、渡邊 嘉之、笠井 清登、橋本 亮太
  • Organizer: 日本統合失調症学会
• [Presentation] Cross-diagnostic Comparisons of Intellectual Ability and Work Outcome in Patients with Mental Disorders: A Multi-center Study (2021)
  • Author(s): Chika Sumiyoshi, Maeri Yamamoto（11番目）, Ryota Hashimoto(25番目）、他22名
  • Organizer: Schizophrenia International Research Society
  • Int'l Joint Research
• [Presentation] Cortical structural mega-analysis across four major psychiatric disorders in 5432 individuals (2021)
  • Author(s): Junya Matsumoto, Maeri Yamamoto(23番目）, Norio Ozaki（40番目）, Ryota Hashimoto（42番目）、他38名
  • Organizer: Asian College of Neuropsychopharmacology
  • Int'l Joint Research
• [Presentation] Structural MRI spatial pattern associated with schizophrenia patients in a multivariate approach (2020)
  • Author(s): 山本真江里
  • Organizer: the26th Annual Meeting of the Organization for Human Brain Mapping
  • Int'l Joint Research
• [Presentation] Structural MRI spatial pattern associated with schizophrenia patients in a multivariate approach (2020)
  • Author(s): 山本真江里
  • Organizer: 第43回日本神経科学大会
• [Presentation] Classification of schizophrenia patients and healthy controls using structural MRI (2019)
  • Author(s): Maeri Yamamoto, Epifanio Bagarinao, Itaru Kusihma, Tsutomu Takahashi, Daiki Sasabayashi, Ryohei Suzuki, Aleksic Branko, Toshiya Inada, Michio Suzuki, Tetsuya Iidaka, Norio Ozaki
  • Organizer: the25th Annual Meeting of the Organization for Human Brain Mapping
  • Int'l Joint Research
• [Presentation] Classification of schizophrenia patients and healthy controls (2019)
  • Author(s): Yamamoto Maeri, Bagarinao Epifanio, Kushima Itaru, Suzuki Ryohei, Branko Aleksic, Inada Toshiya, Iidaka Tetsuya, Ozaki Norio
  • Organizer: Neuroscience 2019
  • Int'l Joint Research
• [Presentation] Aberrant Thalamic Functional Connectivity is Related To Attention Deficit in Schizophnreia (2017)
  • Author(s): 山本真江里
  • Organizer: 日本神経科学大会
• [Presentation] Aberrant functional connectivity between thalamus and visual cortex is related to attentional impairment in schizophrenia (2017)
  • Author(s): 山本真江里
  • Organizer: Neuroscience2017
  • Int'l Joint Research
• [Remarks] Reseachmap
  • URL: https://researchmap.jp/7000031353
• [Remarks] ORCiD
  • URL: https://orcid.org/0000-0002-5239-6225
• [Remarks] 名古屋大学医学部狂院データベース
  • URL: http://profs.provost.nagoya-u.ac.jp/view/html/100009117_ja.html