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Study on vulnerability and predictive factors for neurodevelopmental disorders

Research Project

Project/Area Number 20H03595
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 52030:Psychiatry-related
Research InstitutionHirosaki University

Principal Investigator

Nakamura Kazuhiko  弘前大学, 医学研究科, 教授 (80263911)

Co-Investigator(Kenkyū-buntansha) 上野 伸哉  弘前大学, 医学研究科, 教授 (00312158)
斉藤 まなぶ  弘前大学, 保健学研究科, 教授 (40568846)
古川 智範  弘前大学, 医学研究科, 助教 (60402369)
下山 修司  弘前大学, 医学研究科, 助教 (60736370)
坂本 由唯  弘前大学, 医学部附属病院, 講師 (60770386)
足立 匡基  弘前大学, 保健学研究科, 准教授 (50637329)
高橋 芳雄  弘前大学, 保健学研究科, 准教授 (70760891)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2022: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2021: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2020: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Keywords神経発達症群 / 自閉症 / 注意欠如・多動症 / メタボローム解析 / 5歳児発達健診 / ASD / ADHD / オキシトシン / フェリチン / 神経発達障害 / 自閉スペクトラム症 / 質量分析 / 注意欠如・多動性障害
Outline of Research at the Start

①5歳児発達健診で神経発達障害の診断のついた約650名の5歳児を対象。1)ASD診断ツール、ADHD診断ツール、DCD診断ツールなどの各種ツールのデータ、2)メタボローム解析データ、エクソーム解析データ。これらのデータの変量解析を行い、新しい疾患概念の構築の可能性を明らかにする。
②約650名のデータと小学生1年生から6年生、中学生1年生から3年生の子どものこころのサポート調査の2014年から2019年の臨床データをリンクし、継時的な変化を解析し、神経発達障害から問題行動、各種精神疾患が発症しやすい脆弱性、予測因子を明らかにする。

Outline of Final Research Achievements

The 5-year-old developmental check-up was held annually in a certain city. We analyzed serum, genetic and other data of the neurodevelopmental disorder group for tenth years. Metabolomic analysis of plasma revealed that a group of amino acids had significant differences in ASD, and biogenic amines and fatty acids indicated significant differences in ADHD. Significant differences were found in four factors for the coexistence of ASD and ADHD. Furthermore, a correlation was found between sleep and ferritin in the neurodevelopmental disorder group, and a positive correlation was found between oxytocin levels and Conners' hyperactivity in girls in the ASD group.

Academic Significance and Societal Importance of the Research Achievements

2次発達健診で神経発達障害群の診断がついた5歳児約650名の血漿をメタボローム解析することでASD、ADHDの診断マーカーもしくは病態解明につながる因子がいくつか明らかになった。ASD、ADHDと睡眠やオキシトシン値との関連もわかり、ASDやADHDの病態解明につながる結果が得られたことは学問的意義があり、ASDとADHDは同じ群にあり、臨床的にそれを意識することは臨床的にも意義があり、社会に還元できる。

Report

(4 results)
  • 2023 Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (39 results)

All 2023 2022 2021 2020

All Journal Article (14 results) (of which Int'l Joint Research: 10 results,  Peer Reviewed: 14 results,  Open Access: 14 results) Presentation (24 results) (of which Int'l Joint Research: 12 results,  Invited: 1 results) Book (1 results)

  • [Journal Article] Trajectories of emotional and behavioral problems in school-age children with coordination difficulties and their relationships to ASD/ADHD traits2023

    • Author(s)
      Mikami Misaki、Hirota Tomoya、Adachi Masaki、Takahashi Michio、Nishimura Tomoko、Saito Manabu、Nakamura Kazuhiko、Yamada Junko
    • Journal Title

      Research in Developmental Disabilities

      Volume: 133 Pages: 104394-104394

    • DOI

      10.1016/j.ridd.2022.104394

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Molecular diagnosis of 405 individuals with autism spectrum disorder2023

    • Author(s)
      Miyake Noriko、Tsurusaki Yoshinori、Fukai Ryoko、Kushima Itaru...Takata Atsushi、Mizuguchi Takeshi、Ozaki Norio、Matsumoto Naomichi
    • Journal Title

      European Journal of Human Genetics

      Volume: 27-Mar Issue: 12 Pages: 1-8

    • DOI

      10.1038/s41431-023-01335-7

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The Role of the Maternal and Child Health Handbook in Developmental Surveillance: The Exploration of Milestone Attainment Trajectories2022

    • Author(s)
      Hirota Tomoya、Nishimura Tomoko、Mikami Misaki、Saito Manabu、Nakamura Kazuhiko
    • Journal Title

      Frontiers in Psychiatry

      Volume: 13 Pages: 902158-902158

    • DOI

      10.3389/fpsyt.2022.902158

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cohort Profile: The Assessment from Preschool to Puberty? Longitudinal Epidemiological (APPLE) study in Hirosaki, Japan2021

    • Author(s)
      Hirota, T., Adachi, M., Takahashi, M., Mori, H., Shinkawa, H., Sakamoto, Y., Saito, M., & Nakamura, K.
    • Journal Title

      International Journal of Epidemiology

      Volume: 50 Issue: 6 Pages: 1782-1783

    • DOI

      10.1093/ije/dyab112

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A loss-of-function variant in SUV39H2 identified in autism-spectrum disorder causes altered H3K9 trimethylation and dysregulation of protocadherin β-cluster genes in the developing brain2021

    • Author(s)
      Balan Shabeesh、-25名-, Shinkai Yoichi、Yoshikawa Takeo
    • Journal Title

      Molecular Psychiatry

      Volume: 26 Issue: 12 Pages: 7550-7559

    • DOI

      10.1038/s41380-021-01199-7

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Prevalence and cumulative incidence of autism spectrum disorders and the patterns of co-occurring neurodevelopmental disorders in a total population sample of 5-year-old children2020

    • Author(s)
      Saito Manabu、Hirota Tomoya、Sakamoto Yui、Adachi Masaki、Takahashi Michio、Osato-Kaneda Ayako、Kim Young Shin、Leventhal Bennett、Shui Amy、Kato Sumi、Nakamura Kazuhiko
    • Journal Title

      Molecular Autism

      Volume: 11 Issue: 1 Pages: 35-35

    • DOI

      10.1186/s13229-020-00342-5

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] In vivo imaging of dopamine D1 receptor and activated microglia in attention-deficit/hyperactivity disorder: a positron emission tomography study2020

    • Author(s)
      Yokokura Masamichi、Takebasashi Kiyokazu、Takao Akiyo、Nakaizumi Kyoko、Yoshikawa Etsuji、Futatsubashi Masami、Suzuki Katsuaki、Nakamura Kazuhiko、Yamasue Hidenori、Ouchi Yasuomi
    • Journal Title

      Molecular Psychiatry

      Volume: - Issue: 9 Pages: 12-12

    • DOI

      10.1038/s41380-020-0784-7

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association between Sleep Disturbances and Emotional/Behavioral Problems in Chinese and Japanese Preschoolers.2020

    • Author(s)
      Wang G, Takahashi M, Wu R, Liu Z, Adachi M, Saito M, Nakamura, K, Jiang F.
    • Journal Title

      Behavioral Sleep Medicine

      Volume: 18(3) Issue: 3 Pages: 420-431

    • DOI

      10.1080/15402002.2019.1605995

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Utilization of the Maternal and Child Health Handbook in Early Identification of Autism Spectrum Disorder and Other Neurodevelopmental Disorders2020

    • Author(s)
      Hirota Tomoya、Bishop Somer、Adachi Masaki、Shui Amy、Takahashi Michio、Mori Hiroyuki、Nakamura Kazuhiko
    • Journal Title

      Autism Research

      Volume: 14 Issue: 3 Pages: 551-559

    • DOI

      10.1002/aur.2442

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Neurodevelopmental Traits and Longitudinal Transition Patterns in Internet Addiction: A 2-year Prospective Study2020

    • Author(s)
      Hirota Tomoya、Takahashi Michio、Adachi Masaki、Sakamoto Yui、Nakamura Kazuhiko
    • Journal Title

      Journal of Autism and Developmental Disorders

      Volume: 51 Issue: 4 Pages: 1365-1374

    • DOI

      10.1007/s10803-020-04620-2

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A potential role of fatty acid binding protein 4 in the pathophysiology of autism spectrum disorder.2020

    • Author(s)
      Maekawa M, Ohnishi T, Toyoshima M, Shimamoto-Mitsuyama C, Hamazaki K, Balan S, Wada Y, Esaki K, Takagai S, Tsuchiya KJ, Nakamura K, Iwata Y, Nara T, Iwayama Y, Toyota T, Nozaki Y, Ohba H, Watanabe A, Hisano Y, Matsuoka S, Tsujii M, Mori N, Matsuzaki H, Yoshikawa T.
    • Journal Title

      Brain Communication

      Volume: 2(2) Issue: 2

    • DOI

      10.1093/braincomms/fcaa145

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Concerns for labor analgesia and autism spectrum disorders2020

    • Author(s)
      Saito Manabu、Nakamura Kazuhiko、Hirota Kazuyoshi
    • Journal Title

      Journal of Anesthesia

      Volume: 35 Issue: 2 Pages: 319-320

    • DOI

      10.1007/s00540-020-02880-x

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pediatric health-related quality of life and school social capital through network perspectives2020

    • Author(s)
      Hirota Tomoya、Takahashi Michio、Adachi Masaki、Nakamura Kazuhiko
    • Journal Title

      PLOS ONE

      Volume: 15 Issue: 12 Pages: e0242670-e0242670

    • DOI

      10.1371/journal.pone.0242670

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] VLDL-specific increases of fatty acids in autism spectrum disorder correlate with social interaction.2020

    • Author(s)
      Usui N, Toyoshima M et al.
    • Journal Title

      EBioMedicine

      Volume: 58 Pages: 102917-102917

    • DOI

      10.1016/j.ebiom.2020.102917

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Biological and epidemiological studies of neurodevelopmental disorders2023

    • Author(s)
      Kazuhiko Nakamura
    • Organizer
      ASCAPAP2023
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Association between the Financial Impact of COVID-19 Pandemic and Mental Health of 5 Years Old Children with Neurodevelopmental Traits in Japan2023

    • Author(s)
      Y. Sakamoto , M. Saito , A. Osato , A. Terui , T. Mikami and K. Nakamura
    • Organizer
      INSAR2023
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Prevalence of Sleep Problems in Preschool Children with Neurodevelopmental Disorders and Correlation with Behavioral or Serum Ferritin in Community Surveys A.2022

    • Author(s)
      A Terui, M. Saito , A. Kuki, Y. Sakamoto , T. Mikami , A. Osato and K. Nakamura
    • Organizer
      INSAR2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Responses to COVID-19 Pandemic and Their Associations with Neurodevelopmental Traits in a General Population Sample of 5 Years Old Children in Japan2022

    • Author(s)
      Y. Sakamoto , M. Saito , T. Hirota , A. Osato , A. Terui , T. Mikami and K. Nakamura
    • Organizer
      INSAR2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Relevance of the Plasma Oxytocin Concentration and Neurodevelopmental Disorders in 5-Year-Old Children Considering Gender2021

    • Author(s)
      Y. Sakamoto, M. Saito, A. Osato, A.Terui , K. Yoshida, T. Mikami and K.Nakamura
    • Organizer
      INSAR2021
    • Related Report
      2021 Annual Research Report
  • [Presentation] Verification of New Screening Tools for Neurodevelopmental Disorders in 5-Year-Old Children, Including the Use of Web Systems.2021

    • Author(s)
      A. Terui , M. Saito, M. Adachi, Y. Sakamoto , A. Osato , T. Mikami and K. Nakamura.
    • Organizer
      INSAR2021
    • Related Report
      2021 Annual Research Report
  • [Presentation] シンポジウム「子どものこころの臨床に関する現状と課題」 5歳児発達健診と学校コホートの試み2021

    • Author(s)
      中村和彦、斉藤まなぶ、足立匡基
    • Organizer
      第48回日本脳科学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 未就学児の神経発達障害と睡眠問題;行動、フェリチンとの関係2021

    • Author(s)
      照井藍、斉藤まなぶ、九鬼朝美、坂本由唯、三上珠希、大里絢子、中村和彦
    • Organizer
      第117回日本精神神経学会学術総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 5歳児におけるオキシトシンと神経発達障害の関連と男女差2021

    • Author(s)
      坂本由唯、斉藤まなぶ、大里絢子、照井藍、三上珠希、中村和彦
    • Organizer
      第117回日本精神神経学会学術総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 5歳児の睡眠障害についての疫学分析2021

    • Author(s)
      九鬼朝美、斉藤まなぶ、照井藍、坂本由唯、三上珠希、大里絢子、中村和彦
    • Organizer
      第117回日本精神神経学会学術総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Development of Screening Algorithm for Autism Spectrum Disorder in 5-Year-Old Children Using the Eye-Tracking Device (Gazefinder)2020

    • Author(s)
      Y. Sakamoto, M. Saito, M. Ninomiya, S. Hakoshima, K. J. Tsuchiya, A. Osato, A. Terui, H. Mori, K. Yoshida, Y. Matsubara, T. Mikami, M. Takahashi and K. Nakamura.
    • Organizer
      The International Society for Autism Research (INSAR) 2020 Annual Meeting
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Development of a Screening Algorithm of Neurodevelopmental Disorders for 5-Year-Old Children Toward Web Survey Systemization2020

    • Author(s)
      A. Terui, M. Saito, A. Osato, M. Tanaka, N. Takayanagi, M. Adachi, M. Wakuta, Y. Sakamoto, H. Mori, K. Yoshida, Y. Matsubara, T. Mikami, M. Takahashi, K. Nakamura and Y. Yamamura,
    • Organizer
      The International Society for Autism Research (INSAR) 2020 Annual Meeting
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Utilization of the Maternal and Child Health Handbook in Early Identification of Autism Spectrum Disorder and Other Neurodevelopmental Disorders.2020

    • Author(s)
      T Hirota, S. Bishop, M. Adachi, M. Takahashi, H. Mori, A. M. Shui and K. Nakamura
    • Organizer
      The International Society for Autism Research (INSAR) 2020 Annual Meeting
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] White Matter Structure Relates to Delayed Processing Speed for the Planning Task and in ASD without Intellectual Disability.2020

    • Author(s)
      M. Takahashi, Y. Matsubara and K. Nakamura.
    • Organizer
      The International Society for Autism Research (INSAR) 2020 Annual Meeting
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Creation of eye tracking pattern algorithm for 5 year old ASD screening.2020

    • Author(s)
      Saito Manabu, Ninomiya Masaru,Hakoshima Shuji, Tsuchiya Kenji, Osato Kaneda Ayako Mikami Tamaki, Sakamoto Yui , Yoshida Kazutaka , Terui Ai, Nakamura Kazuhiko.
    • Organizer
      NPBPPP2020 (第50回日本神経精神薬理学会年会・第42回日本生物学的精神医学会年会・第4回日本精神薬学会総会・学術集会 合同年会)
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 5歳児発達健診 Web スクリーニングシステム(ここあぽ)の完成2020

    • Author(s)
      斉藤 まなぶ、田中 勝則 、山村 靖彦 、和久田 学、大里 絢子、足立 匡基、三上 珠希 、 坂本 由唯 、照井 藍 、森 裕幸、新川 広樹 、高橋 芳雄、栗林 理人、中村 和彦
    • Organizer
      第116回日本精神神経学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Utilization of web screening system for developmental health check&-up in 5-yea-old children 5歳児発達健診でのWebスクリーニングシステムの活用2020

    • Author(s)
      斉藤まなぶ、田中勝則、大里絢子、足立匡基、坂本由唯、三上珠希、照井藍、鈴木裕幸、新川広樹、高橋芳雄、中村和彦
    • Organizer
      第62回日本小児神経学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 視点追跡装置(Gaze Finder)を用いた5歳児のASDスクリーニングアルゴリズムの開発2020

    • Author(s)
      斉藤まなぶ、坂本由唯、三上珠希、大里絢子、照井藍、中村和彦
    • Organizer
      第61回日本児童青年精神医学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 3歳児健診における簡便かつ鋭敏な神経発達症のスクリーニング法の探索2020

    • Author(s)
      大里 絢子, 斉藤 まなぶ, 坂本 由唯, 三上 珠希, 足立 匡基, 中村 和彦
    • Organizer
      第61回日本児童青年精神医学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 5歳児発達健診でのwebスクリーニングシステムの活用2020

    • Author(s)
      照井 藍, 斉藤 まなぶ, 田中 勝則, 大里 絢子, 足立 匡基, 坂本 由唯, 三上 珠希, 栗林 理人, 中村 和彦
    • Organizer
      第61回日本児童青年精神医学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 地域における5歳の自閉スペクトラム症の疫学調査 調整有病率と累積発生率2020

    • Author(s)
      斉藤 まなぶ, 坂本 由唯, 足立 匡基, 高橋 芳雄, 大里 絢子, 三上 珠希, 照井 藍, 栗林 理人, 中村 和彦
    • Organizer
      第61回日本児童青年精神医学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Prevalence of sleep problems in Japanese preschoolers and children with developmental disabilities.2020

    • Author(s)
      M Saito, M* Takahashi, A Terui, Y Sakamoto, M Adachi, H Shinkawa, H Mori, K Nakamura.
    • Organizer
      IACAPAP2020
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Comorbid rate of sleep problems and the characteristics in Japanese 5-yearold ASD children2020

    • Author(s)
      "Ai Terui*, Manabu Saito, Yui Sakamoto, Tomoya Hirota , Michio Takahashi, Tamaki Mikami, Hiroki Shinkawa, Kazuhiko Nakamura"
    • Organizer
      IACAPAP2020
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] "Plasma Oxytocin and Developmental Disorders in Japanese 5-year-old children"2020

    • Author(s)
      "Yui Sakamoto*, Manabu Saito, Shuji Shimoyama, Ayako Osato, Ai Terui, Kazutaka Yoshida, Tamaki Mikami, Kazuhiko Nakamura"
    • Organizer
      IACAPAP2020
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Book] 子どものこころの診療のコツ 研究のコツ2023

    • Author(s)
      中村和彦編
    • Total Pages
      223
    • Publisher
      金剛出版
    • ISBN
      9784772420068
    • Related Report
      2022 Annual Research Report

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Published: 2020-04-28   Modified: 2026-03-25  

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