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Dissecting the prefrontal cortex dysfunction and its recovery in autism spectrum disorder.

Research Project

Project/Area Number 16H05377
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Psychiatric science
Research InstitutionNara Medical University

Principal Investigator

Makinodan Manabu  奈良県立医科大学, 医学部, 准教授 (00510182)

Co-Investigator(Kenkyū-buntansha) 紀本 創兵  奈良県立医科大学, 医学部, 講師 (00405391)
芳野 浩樹  奈良県立医科大学, 医学部, 准教授 (10347560)
太田 豊作  奈良県立医科大学, 医学部, 学内講師 (10553646)
安野 史彦  国立研究開発法人国立長寿医療研究センター, 病院, 医長 (60373388)
松田 康裕  奈良県立医科大学, 医学部, 助教 (70445063)
Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2019: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2018: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Keywords自閉スペクトラム症 / 前頭前野 / 小児期体験 / リハビリテーション / 社会性 / 髄鞘形成 / 社会的経験 / MRI / 認知リハビリテーション / ミエリン / 自閉症 / 前頭前野機能 / 恐怖記憶
Outline of Final Research Achievements

The main purpose of this study was to clarify the structural and functional abnormalities of the prefrontal cortex in adult autism spectrum disorder (ASD) and to establish a method to improve the prefrontal cortex abnormalities. In this study, we considered that childhood experiences of ASD individuals are different from those of typically developed individuals, and conducted research on the impact of childhood experiences of ASD individuals on prefrontal pathology in mice and humans. Mouse studies reveal that juvenile experience activates microglia in the cerebral cortex and environmental intervention can improve prefrontal myelination defects, demonstrating the importance of childhood experiences. From human studies, we have been able to clarify multiple ASD biomarkers and brain circuits that regulate ASD symptoms by using blood and cutting-edge neuroimaging techniques.

Academic Significance and Societal Importance of the Research Achievements

自閉スペクトラム症(ASD)は社会的な問題となっているものの、決定的な治療法はみつかっておらず、その開発は喫緊の課題である。本研究では従来のようにASD病態を定型発達者と比較することで明らかにするのではなく、その小児期体験に着目することで新規知見を得るよう試みた。不良な小児期体験がこれまでに報告されたASD者で認められる諸症状の一部を引き起こすことが明らかになり、ASD者の小児期体験を調整することによるASD症状の軽減が得られる可能性が示された。ASDの諸症状はペアレントトレーニングやソーシャルスキルトレーニングなどの早期介入によって軽減されるが、本研究結果はそれを支持するものである。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (25 results)

All 2020 2019 2018 2017

All Journal Article (14 results) (of which Peer Reviewed: 13 results,  Open Access: 13 results) Presentation (10 results) (of which Int'l Joint Research: 3 results) Book (1 results)

  • [Journal Article] Microstructural Anomalies Evaluated by Neurite Orientation Dispersion and Density Imaging Are Related to Deficits in Facial Emotional Recognition via Perceptual-Binding Difficulties in Autism Spectrum Disorder2020

    • Author(s)
      Fumihiko Yasuno 1 2 , Manabu Makinodan 1 , Masato Takahashi 1 , Kiwamu Matsuoka 1 , Hiroaki Yoshikawa 1 , Soichiro Kitamura 1 , Rio Ishida 1 , Naoko Kishimoto 1 , Toshiteru Miyasaka 3 , Kimihiko Kichikawa 3 , Toshifumi Kishimoto 1
    • Journal Title

      Autism Res

      Volume: 13 Issue: 5 Pages: 729-740

    • DOI

      10.1002/aur.2280

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Delayed Prefrontal Hemodynamic Response Associated With Suicide Risk in Autism Spectrum Disorder2020

    • Author(s)
      Ota T, Iida J, Okazaki K, Ishida R, Takahashi M, Okamura K, Yamamuro K, Kishimoto N, Kimoto S, Yasuda Y, Hashimoto R, Makinodan M, Kishimoto T.
    • Journal Title

      Psychiatry Res

      Volume: 289 Pages: 112971-112971

    • DOI

      10.1016/j.psychres.2020.112971

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Juvenile Social Isolation Enhances the Activity of Inhibitory Neuronal Circuits in the Medial Prefrontal Cortex.2020

    • Author(s)
      Yamamuro K, Yoshino H, Ogawa Y, Okamura K, Nishihata Y, Makinodan M, Saito Y, Kishimoto T
    • Journal Title

      Front Cell Neurosci

      Volume: 14 Pages: 105-105

    • DOI

      10.3389/fncel.2020.00105

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Increased dendritic orientationdispersion in the left occipital gyrus is associated with atypical visual processing in adults with autism spectrum disorder2020

    • Author(s)
      1.Matsuoka K, Makinodan M*, Kitamura S, Takahashi M, Yoshikawa H, Yasuno F, Ishida R, Kishimoto N,Yasuda Y, Hashimoto R, Taoka T, Miyasaka T, Kichikawa K, Kishimoto T
    • Journal Title

      Cereb Cortex

      Volume: in press

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Characterization of behavioral phenotypes in the BTBR <i>T<sup>+</sup> Itpr3<sup>tf</sup></i>/J mouse model of autism spectrum disorder under social housing conditions using the multiple animal positioning system2019

    • Author(s)
      Endo N, Makinodan M*, Somayama N, Komori T, Kishimoto T, Nishi M*
    • Journal Title

      Experimental Animals

      Volume: 68 Issue: 3 Pages: 319-330

    • DOI

      10.1538/expanim.18-0177

    • NAID

      130007689880

    • ISSN
      0007-5124, 1341-1357, 1881-7122
    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anti-inflammatory Effect of Ghrelin in Lymphoblastoid Cell Lines From Children With Autism Spectrum Disorder2019

    • Author(s)
      Yamashita Yasunori、Makinodan Manabu、Toritsuka Michihiro、Yamauchi Takahira、Ikawa Daisuke、Kimoto Sohei、Komori Takashi、Takada Ryohei、Kayashima Yoshinori、Hamano-Iwasa Kaori、Tsujii Masatsugu、Matsuzaki Hideo、Kishimoto Toshifumi
    • Journal Title

      Frontiers in Psychiatry

      Volume: 10 Pages: 152-152

    • DOI

      10.3389/fpsyt.2019.00152

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anti-inflammatory Effect of Ghrelin in Lymphoblastoid Cell Lines From Children With Autism Spectrum Disorder2019

    • Author(s)
      Yasuhiro Matsuda 1 , Manabu Makinodan 1 , Tsubasa Morimoto 1 , Toshifumi Kishimoto
    • Journal Title

      Psychiatry Clin Neurosci

      Volume: 73 Issue: 11 Pages: 676-684

    • DOI

      10.1111/pcn.12912

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Social Status and Modern-Type Depression: A Review2019

    • Author(s)
      Takashi Komori 1 , Manabu Makinodan 1 , Toshifumi Kishimoto 1
    • Journal Title

      Brain Behav

      Volume: 9 Issue: 12

    • DOI

      10.1002/brb3.1464

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Self-Construal Scale: A Potential Tool for Predicting Subjective Well-Being of Individuals With Autism Spectrum Disorder2019

    • Author(s)
      Sachie Kaneko 1 2 3 , Takahiro A Kato 1 , Manabu Makinodan 4 , Takashi Komori 4 , Rio Ishida 4 , Naoko Kishimoto 4 , Masato Takahashi 4 , Yuka Yasuda 4 5 6 , Ryota Hashimoto 6 7 , Hidemi Iwasaka 3 , Ayumi Tanaka 8 , Yukiko Uchida 2 , Shigenobu Kanba 1 , Toshifumi Kishimoto 4
    • Journal Title

      Autism Res

      Volume: in press Issue: 6 Pages: 947-958

    • DOI

      10.1002/aur.2242

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Altered gene expression in lymphoblastoid cell lines after subculture.2018

    • Author(s)
      Toritsuka M, Makinodan M, Yamauchi T, Yamashita Y, Ikawa D, Komori T, Kimoto S, Hamano-Iwasa K, Matsuzaki H, Kishimoto T.
    • Journal Title

      In Vitro Cell. Dev. Biol. Anim.

      Volume: 54 Issue: 7 Pages: 523-527

    • DOI

      10.1007/s11626-018-0267-1

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Multiple animal positioning system shows that socially-reared mice influence the social proximity of isolation-reared cagemates.2018

    • Author(s)
      Endo N, Ujita W, Fujiwara T, Miyauchi H, Mishima H, Makino Y, Hashimoto L, Oyama, H, Makinodan M, Nishi M, Tohyama C, Kakeyama M*
    • Journal Title

      Communications Biology

      Volume: 1 Issue: 1 Pages: 225-225

    • DOI

      10.1038/s42003-018-0213-5

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Computer-assisted cognitive remediation therapy increases hippocampal volume in patients with schizophrenia: a randomized controlled trial2018

    • Author(s)
      Tsubasa Morimoto, Yasuhiro Matsuda, Kiwamu Matsuoka, Fumihiko Yasuno, Emi Ikebuchi, Hiroyuki Kameda, Toshiaki Taoka, Toshiteru Miyasaka, Kimihiko Kichikawa and Toshifumi Kishimoto
    • Journal Title

      BMC Psychiatry

      Volume: 18 Issue: 1 Pages: 1-8

    • DOI

      10.1186/s12888-018-1667-1

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of the mode of re-socialization after juvenile social isolation on medial prefrontal cortex myelination and function2017

    • Author(s)
      Makinodan M. Ikawa D. Yamamuro K. Yamashita Y. Torituka M. Kimoto S. Okumura K. Komori T. Fukami S. Yoshino H. Kanba S. Wanaka A. Kishimoto T
    • Journal Title

      Sci.Rep

      Volume: 14 Issue: 1 Pages: 5481-5481

    • DOI

      10.1038/s41598-017-05632-2

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of cross-rearing with social peers on myelination in the medial prefrontal cortex of a mouse model with autism spectrum disorder2017

    • Author(s)
      Makinodan M. Okumura K. Ikawa D. Yamashita Y. Yamamuro K. Toritsuka M. Kimoto S. Yamauchi T. Komori T. Kayashima Y. Yoshino H. Wanaka A. Kishimoto T.
    • Journal Title

      Heliyon

      Volume: 3 Issue: 11 Pages: e00468-e00468

    • DOI

      10.1016/j.heliyon.2017.e00468

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Increased dendritic orientationdispersion in the left occipital gyrus is associated with atypical visual processing in adults with autism spectrum disorder2019

    • Author(s)
      Makinodan M
    • Organizer
      World Psychiatric Association
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Increased dendritic orientationdispersion in the left occipital gyrus is associated with atypical visual processing in adults with autism spectrum disorder2019

    • Author(s)
      牧之段学
    • Organizer
      日本神経薬理学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 自閉スペクトラム症の免疫異常とミエリン形成障害2018

    • Author(s)
      牧之段学
    • Organizer
      日本生物学的精神医学会・日本神経化学会合同年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 自殺と脳科学2018

    • Author(s)
      牧之段学
    • Organizer
      日本自殺予防学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 幼少期社会的経験と前頭前野2018

    • Author(s)
      牧之段学
    • Organizer
      日本生物学的精神医学会・日本神経化学会合同年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Jcoresを用いた認知機能リハビリテーションプログラム(VCAT-J)の紹介~SSTとの統合的実施を目指して~2017

    • Author(s)
      松田康裕 盛本翼
    • Organizer
      第23回全国経験交流ワークショップ
    • Related Report
      2017 Annual Research Report
  • [Presentation] 就労支援に役立つ認知機能リハビリテーション(VCAT-J)2017

    • Author(s)
      松田康裕、梅田典子、佐藤さやか、岸本年史
    • Organizer
      就労支援に役立つ認知機能リハビリテーション(VCAT-J)
    • Related Report
      2017 Annual Research Report
  • [Presentation] Computer-assisted cognitive remediation therapy increases hippocampal volume in schizophrenia2017

    • Author(s)
      Morimoto T, Matsuda Y, Matsuoka K, et al.
    • Organizer
      WPA XVII WORLD CONGRESS OF PSYCHIATRY
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Shared glial contributions to the etiology of autism and schizophrenia.2017

    • Author(s)
      Makinodan M
    • Organizer
      World Congress of Biological Psychiatry
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 日本人研究者による自閉スペクトラム症の生物学的研究2017

    • Author(s)
      牧之段学
    • Organizer
      日本児童青年精神医学会総会
    • Related Report
      2017 Annual Research Report
  • [Book] 統合失調症の最近の進歩2018

    • Author(s)
      松田 康裕
    • Total Pages
      4
    • Publisher
      Medical Science Digest
    • Related Report
      2017 Annual Research Report

URL: 

Published: 2016-04-21   Modified: 2021-02-19  

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