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Imaging epigenome-wide association study to identify biomarkers for child maltreatment

Research Project

Project/Area Number 20K02700
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 09030:Childhood and nursery/pre-school education-related
Research InstitutionUniversity of Fukui

Principal Investigator

Nishitani Shota  福井大学, 子どものこころの発達研究センター, 特命講師 (50448495)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords虐待 / マルトリートメント / エピゲノム / MRI / 子ども / DNAメチル化 / 脳 / 遺伝子 / トラウマ / エピジェネティクス / ゲノムワイド解析
Outline of Research at the Start

マルトリートメントの早期介入・治療が望まれていながらも、Mal児当事者を対象とした研究は、未成年である当事者の親権者からの研究同意が得られない等、研究実施が極めて困難なことから、治療の根幹をなす標的分子機序も定まっていない。近年、マルトリートメントがDNAメチル化のエピジェネティックな変化を刻み、それが生涯に渡る脳の脆弱性に関連することを示唆する研究が行われてきた。しかし、かつてマルトリートメントを受けた成人研究が主で、Mal児当事者を対象としたものはごく僅かである。そこで、本研究では、エピジェネティクス、脳MRI、両者を組み合わせた脳画像エピゲノムから、Mal児のバイオマーカー開発を行う。

Outline of Final Research Achievements

In addition to the existing data, additional samples and data were consolidated and cleaned, resulting in a data set (brain MRI and saliva methylation microarray) of 61 maltreatment children and 62 typically developed children. The epigenome-wide analysis identified 16 genome-wide significant DMPs, but no significant DMRs were detected. We also conducted a GAMuT analysis, a genome-wide comparison of each gene unit, and found that the gene containing one location in the DMP was significantly associated. In relation to brain MRI, this methylation was found to correlate negatively with the fusiform gyrus of the occipital lobe.

Academic Significance and Societal Importance of the Research Achievements

マルトリートメント児、及び同年代の定型発達児の脳MRI、唾液メチル化アレイデータの両者が揃った、世界有数かつ本邦一の規模となるデータセットが構築された。これは今後、多くの研究者らに活用される二次データとしての学術的な利用価値も高い。代表者の一次解析の結果では、マルトリートメントに関連した複数のメチル化部位が明らかにされた。それらメチル化部位や遺伝子と、幼少期のマルトリートメントとを、データ駆動型解析から結びつけた功績は、学術的に貢献度が高い。今後、マルトリートメントに曝された子どもの早期発見に資するバイオマーカーとなる視点についての検討も行うことで、社会的意義にも多大な貢献をする可能性が高い。

Report

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

    (28 results)

All 2023 2022 2021 2020 Other

All Int'l Joint Research (5 results) Journal Article (14 results) (of which Int'l Joint Research: 9 results,  Peer Reviewed: 14 results,  Open Access: 10 results) Presentation (6 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Book (1 results) Remarks (2 results)

  • [Int'l Joint Research] Stanford University(米国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] Emory University(米国)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] Korea Brain Research Institute(韓国)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] University of Malaya(マレーシア)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] Emory University/University of Georgia/The University of Toledo(米国)

    • Related Report
      2020 Research-status Report
  • [Journal Article] Cross-tissue correlations of genome-wide DNA methylation in Japanese live human brain and blood, saliva, and buccal epithelial tissues.2023

    • Author(s)
      Nishitani S, Isozaki M, Yao A, Higashino Y, Yamauchi T, Kidoguchi M, Kawajiri S, Tsunetoshi K, Neish H, Imoto H, Arishima H, Kodera T, Fujisawa TX, Nomura S, Kikuta K, Shinozaki G, Tomoda A.
    • Journal Title

      Transl Psychiatry

      Volume: 13 Issue: 1 Pages: 72-72

    • DOI

      10.1038/s41398-023-02370-0

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effects of intranasal oxytocin on neural reward processing in children and adolescents with reactive attachment disorder: A randomized controlled trial2023

    • Author(s)
      Takiguchi Shinichiro、Makita Kai、Fujisawa Takashi X.、Nishitani Shota、Tomoda Akemi
    • Journal Title

      Frontiers in Child and Adolescent Psychiatry

      Volume: 1 Pages: 1-16

    • DOI

      10.3389/frcha.2022.1056115

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Association of Epigenetic Differences Screened in a Few Cases of Monozygotic Twins Discordant for Attention-Deficit Hyperactivity Disorder With Brain Structures2022

    • Author(s)
      Fujisawa Takashi X.、Nishitani Shota、Makita Kai、Yao Akiko、Takiguchi Shinichiro、Hamamura Shoko、Shimada Koji、Okazawa Hidehiko、Matsuzaki Hideo、Tomoda Akemi
    • Journal Title

      Frontiers in Neuroscience

      Volume: 15 Pages: 1-12

    • DOI

      10.3389/fnins.2021.799761

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The effects of epigenetic age and its acceleration on surface area, cortical thickness and volume in young adults.2022

    • Author(s)
      Cheong Y, Nishitani S, Yu J, Habata K, Kamiya T, Shiotsu D, Omori IM, Okazawa H, Tomoda A, Kosaka H, Jung M.
    • Journal Title

      Cereb Corte

      Volume: in press Issue: 24 Pages: 043-043

    • DOI

      10.1093/cercor/bhac043

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Epigenetic Clock Deceleration and Maternal Reproductive Efforts: Associations With Increasing Gray Matter Volume of the Precuneus.2022

    • Author(s)
      Nishitani S, Kasaba R, Hiraoka D, Shimada K, Fujisawa TX, Okazawa H, Tomoda A.
    • Journal Title

      Front Genet.

      Volume: 12 Pages: 803584-803584

    • DOI

      10.3389/fgene.2022.803584

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A multi-modal MRI analysis of brain structure and function in relation to OXT methylation in maltreated children and adolescents2021

    • Author(s)
      Nishitani Shota、Fujisawa Takashi X.、Hiraoka Daiki、Makita Kai、Takiguchi Shinichiro、Hamamura Shoko、Yao Akiko、Shimada Koji、Smith Alicia K.、Tomoda Akemi
    • Journal Title

      Translational Psychiatry

      Volume: 11 Issue: 1 Pages: 1-9

    • DOI

      10.1038/s41398-021-01714-y

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Influence of the COVID-19 Pandemic on Parenting Stress Across Asian Countries: A Cross-National Study.2021

    • Author(s)
      Kurata S, Hiraoka D, Ahmad Adlan AS, Jayanath S, Hamzah N, Ahmad-Fauzi A, Fujisawa TX, Nishitani S, Tomoda A.
    • Journal Title

      Front Psychol.

      Volume: 12 Pages: 782298-782298

    • DOI

      10.3389/fpsyg.2021.782298

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Altered epigenetic clock in children exposed to maltreatment.2021

    • Author(s)
      Nishitani S, Suzuki S, Ochiai K, Yao A, Fujioka T, Fujisawa TX, Tomoda A.
    • Journal Title

      Psychiatry Clin Neurosci.

      Volume: 75 Issue: 3 Pages: 110-112

    • DOI

      10.1111/pcn.13183

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epigenetic modification of the oxytocin gene is associated with gray matter volume and trait empathy in mothers2021

    • Author(s)
      Hiraoka D, Nishitani S, Shimada K, Kasaba R, Fujisawa TX, Tomoda A.
    • Journal Title

      Psychoneuroendocrinology.

      Volume: 123 Pages: 105026-105026

    • DOI

      10.1016/j.psyneuen.2020.105026

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epigenetic prediction of 17β-estradiol and relationship to trauma-related outcomes in women2021

    • Author(s)
      Hack LM, Nishitani S, Knight AK, Kilaru V, Maddox SA, Seligowski AV, Jovanovic T, Ressler KJ, Smith AK, Michopoulos V
    • Journal Title

      Comprehensive Psychoneuroendocrinology

      Volume: 6 Pages: 100045-100045

    • DOI

      10.1016/j.cpnec.2021.100045

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Mismatch negativity of preschool children at risk of developing mental health problems2021

    • Author(s)
      Aoi T, Fujisawa TX, Nishitani S, Tomoda A.
    • Journal Title

      Neuropsychopharmacol Rep.

      Volume: - Issue: 2 Pages: 1-7

    • DOI

      10.1002/npr2.12168

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epigenetic modification of the oxytocin receptor gene: implications for autism symptom severity and brain functional connectivity2020

    • Author(s)
      Andari E, Nishitani S, Kaundinya G, Caceres GA, Morrier MJ, Ousley O, Smith AK, Cubells JF, Young LJ
    • Journal Title

      Neuropsychopharmacology

      Volume: 45(7) Issue: 7 Pages: 1150-1158

    • DOI

      10.1038/s41386-020-0610-6

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Pathways linking adverse environments to emerging adults' substance abuse and depressive symptoms: A prospective analysis of rural African American men2020

    • Author(s)
      Kogan SM, Bae D, Cho J, Smith AK, Nishitani S
    • Journal Title

      Developmental Psychopathology

      Volume: なし Issue: 4 Pages: 1-11

    • DOI

      10.1017/s0954579420000632

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Methylation of OXT and OXTR genes, central oxytocin, and social behavior in female macaques2020

    • Author(s)
      De Leon D, Nishitani S, Walum H, McCormack KM, Wilson ME, Smith AK, Young LJ, Sanchez MM
    • Journal Title

      Hormones and Behavior

      Volume: 126 Pages: 104856-104856

    • DOI

      10.1016/j.yhbeh.2020.104856

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 社会性とエピジェネティクス2022

    • Author(s)
      西谷正太
    • Organizer
      日本社会心理学会第63回大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] A cross-national study of the influences of COVID-19 pandemic on parenting stress across Asian countries2021

    • Author(s)
      Shota Nishitani
    • Organizer
      The 2nd International Symposium for CRNACDD
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Epigenetic modulation of OXT and OXTR genes in humans2021

    • Author(s)
      Shota Nishitani
    • Organizer
      The 33rd Meeting of the Japanese Society for Behavioral Neuroendocrinology
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Oxytocin and oxytocin receptor DNA methylation modulates social behaviors in humans2020

    • Author(s)
      Shota Nishitani
    • Organizer
      The 43rd Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2020 Research-status Report
  • [Presentation] 被虐待児のOXTR遺伝子DNAメチル化の脳画像エピゲノム解析2020

    • Author(s)
      西谷正太, 友田明美
    • Organizer
      第116回日本精神神経学会学術総会
    • Related Report
      2020 Research-status Report
  • [Presentation] 社会環境による ヒトの社会性への影響2020

    • Author(s)
      西谷正太
    • Organizer
      日本社会心理学会第61回大会
    • Related Report
      2020 Research-status Report
  • [Book] Chapter 16 - Capturing the epigenome: Differences among blood, saliva, and brain samples, Epigenetics of Stress and Stress Disorders2022

    • Author(s)
      Nishitani Shota
    • Total Pages
      420
    • Publisher
      Elsevier (Academic Press)
    • ISBN
      9780128230398
    • Related Report
      2021 Research-status Report
  • [Remarks] AMAZE-CpG

    • URL

      https://snishit-amaze-cpg.web.app/

    • Related Report
      2022 Annual Research Report
  • [Remarks] meVBM

    • URL

      https://snishit-mevbm.web.app/

    • Related Report
      2022 Annual Research Report

URL: 

Published: 2020-04-28   Modified: 2024-01-30  

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