Neurobiological basis of autism spectrum disorders focuslng of reflexive responses to social stimuli

• Project/Area Number: 16K10248
• 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: Okada Takashi 名古屋大学, 医学部附属病院, 准教授 (80335249)
• Co-Investigator(Kenkyū-buntansha): 鈴木 太 福井大学, 子どものこころの発達研究センター, 准教授 (30542683) ; 宇野 洋太 名古屋大学, 医学部附属病院, 助教 (40539681) ; 森川 真子 名古屋大学, 医学系研究科, 寄附講座助教 (60783305) ; 小川 しおり 名古屋大学, 医学部附属病院, 助教 (60814150)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2016: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 自閉スペクトラム症 / 情動的表情認知 / 社会性障害 / 中間表現型 / ゲノムコピー数変異 / アイカメラ / 脳画像 / 表情認識 / 表情表出 / 対人関係障害 / 誤認識パターン / 不適応行動 / 表情認知 / 視線認知 / 反射的応答

Outline of Final Research Achievements

Impaired facial expression recognition disorder is considered to be the most core deficits associated with social disturbances in autism spectrum disorders, but it is also recognized in other disorders such as schizophrenia. We sought to identify a specific pattern of facial affect recognition in autism spectrum disorders, which could clarify the relationship between etiology and pathology. Examination of facial expression recognition patterns in adult men with autism spectrum disorder showed cognitive decline of negative emotions such as anger, disgust, and fear. Adninistration of oxytocin reduced misrecognition between anger and disgust. In addition, we identified rare genomic copy number mutations associated with onset of autism spectrum disorders and accumulated brain imaging and fMRI data.

Academic Significance and Societal Importance of the Research Achievements

本研究の結果から、自閉スペクトラム症では恐怖と怒りの誤認が認められ、それが社会における不適応行動とも関連する障害特異的な表情認識障害である可能性が示唆された。この結果は中間表現型としての有用性と関連しており、今回明らかにしえた稀なゲノムコピー数変異や集積中の脳画像所見とともに併せて解析することで、診断の細分化、診断基準の明確化、病態と関連した個別医療の可能性に道を開くものと思われる。

Research Products

• [Journal Article] Effect of continuing and discontinuing medications on quality of life after symptomatic remission in attention-deficit/hyperactivity disorder: a systematic review and meta-analysis (2020)
  • Author(s): Tsujii N, Okada T, Usami M, Kuwabara H, Fujita J, Negoro H, Kawamura M, Iida J, Saito T
  • Journal Title: The Journal of Clinical Psychiatry Volume: 81 Issue: 3 Pages: 19-27
  • DOI: 10.4088/jcp.19r13015
  • Peer Reviewed / Open Access
• [Journal Article] 児童・青年への抗精神病薬の代謝・内分泌系リスクと求められる副作用モニタリング・スケジュール (2020)
  • Author(s): 藤田純一、宇佐美政英、岡田 俊、辻井農亜、根來秀樹、齊藤卓弥、飯田順三
  • Journal Title: 児童精神医学とその近接領域 Volume: 印刷中
  • NAID: 40022263270
  • Peer Reviewed
• [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] Methylation analysis for postpartum depression : a case control study. (2019)
  • Author(s): Nakamura Y, Nakatochi M, Kunimoto S, Okada T, Aleksic B, Toyama M, Shiino T, Morikawa M, Yamauchi A, Yoshimi A, Furukawa-Hibi Y, Nagai T, Ohara M, Kubota C, Yamada K, Ando M, Ozaki N.
  • Journal Title: BMC Psychiatry. Volume: 19 Issue: 1 Pages: 190-199
  • DOI: 10.1186/s12888-019-2172-x
  • Peer Reviewed / Open Access
• [Journal Article] Changes in tryptophan metabolism during pregnancy and postpartum periods: Potential involvement in postpartum depressive symptoms (2019)
  • Author(s): Teshigawara Tomoaki、Mouri Akihiro、Kubo Hisako、Nakamura Yukako、Shiino Tomoko、Okada Takashi、Morikawa Mako、Nabeshima Toshitaka、Ozaki Norio、Yamamoto Yasuko、Saito Kuniaki
  • Journal Title: Journal of Affective Disorders Volume: 255 Pages: 168-176
  • DOI: 10.1016/j.jad.2019.05.028
  • Peer Reviewed
• [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] Effect of intranasal oxytocin on the core social symptoms of autism spectrum disorder: a randomized clinical trial (2018)
  • Author(s): Yamasue H, Okada T, Munesue T, Kuroda M, Fujioka T, Uno Y, Matsumoto K, Kuwabara H, Mori D, Okamoto Y, Yoshimura Y, Kawakubo Y, Arioka Y, Kojima M, Yuhi T, Owada K, Yassin W, Kushima I, Benner S, Ogawa N, Eriguchi Y, Kawano N, Uemura Y, Yamamoto M, Kano Y, Kasai K, Higashida H, Ozaki N, Kosaka H
  • Journal Title: Molecular Psychiatry Volume: Jan Issue: 8 Pages: 1849-1858
  • DOI: 10.1038/s41380-018-0097-2
  • Peer Reviewed / Open Access
• [Journal Article] Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder (2018)
  • Author(s): Takata A, Miyake N, Tsurusaki Y, Fukai R, Miyatake S, Koshimizu E, Kushima I, Okada T, ...Matsumoto N.
  • Journal Title: Cell Reports Volume: 22(3) Issue: 3 Pages: 734-747
  • DOI: 10.1016/j.celrep.2017.12.074
  • Peer Reviewed / Open Access
• [Journal Article] Possible involvement of a cell adhesion molecule, Migfilin, in brain development and pathogenesis of autism spectrum disorders (2017)
  • Author(s): Ishizuka Kanako、Tabata Hidenori、Ito Hidenori、Kushima Itaru、Noda Mariko、Yoshimi Akira、Usami Masahide、Watanabe Kyota、Morikawa Mako、Uno Yota、Okada Takashi、Mori Daisuke、Aleksic Branko、Ozaki Norio、Nagata Koh-ichi
  • Journal Title: Journal of Neuroscience Research Volume: 96 Issue: 5 Pages: 789-802
  • DOI: 10.1002/jnr.24194
  • Peer Reviewed / Open Access
• [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] 強迫、常同、反復ー強迫症と自閉スペクトラム症ー (2017)
  • Author(s): 岡田俊
  • Journal Title: 精神科治療学 Volume: 32(1) Pages: 103-106
• [Journal Article] Aripiprazole in the treatment of irritability in children and adolescents with autism spectrum disorder in Japan: A randomized, double-blind, placebo-controlled study. (2016)
  • Author(s): Ichikawa H, Mikami K, Okada T, Yamashita Y, Ishizaki Y, Tomoda A, Ono H, Usuki C, Tadori Y.
  • Journal Title: Child Psychiatry Hum Dev Volume: 7(6) Issue: 5 Pages: 841-851
  • DOI: 10.1007/s10578-016-0704-x
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 自閉スペクトラム症の薬物療法 (2016)
  • Author(s): 岡田俊
  • Journal Title: 精神科 Volume: 29(5) Pages: 400-405
• [Journal Article] Investigation of single-nucleotide variants in MBD5 associated with autism spectrum disorders and schizophrenia phenotypes (2016)
  • Author(s): Kanako Ishizuka, Hiroki Kimura, Akira Yoshimi, Masahiro Banno, Itaru Kushima, Yota Uno, Takashi Okada, Daisuke Mori, Branko Aleksic, Norio Ozaki
  • Journal Title: Nagoya Journal of Medical Science Volume: 78 Issue: 4 Pages: 465-474
  • DOI: 10.18999/nagjms.78.4.465
  • NAID: 120005889989
  • ISSN: 2186-3326
  • URL: https://nagoya.repo.nii.ac.jp/records/22947
  • Peer Reviewed / Open Access
• [Journal Article] Investigation of Rare Single-Nucleotide PCDH15 Variants in Schizophrenia and Autism Spectrum Disorders (2016)
  • Author(s): Ishizuka, K., H. Kimura, C. Wang, J. Xing, I. Kushima, Y. Arioka, T. Oya-Ito, Y. Uno, T. Okada, D. Mori, B. Aleksic, and N. Ozaki.
  • Journal Title: PLoS One Volume: 11 Issue: 4 Pages: e0153224-e0153224
  • DOI: 10.1371/journal.pone.0153224
  • Peer Reviewed / Open Access
• [Presentation] 自閉スペクトラム症と併存症のつながりとつらなり-不安、抑うつ、強迫 (2019)
  • Author(s): 岡田 俊
  • Organizer: 第60回日本児童青年精神医学会総会
  • Invited
• [Presentation] 自閉スペクトラム症と併存症のつながりとつらなり-不安、抑うつ、強迫 (2019)
  • Author(s): 岡田 俊
  • Organizer: 第32回日本総合病院精神医学会総会.
  • Invited
• [Presentation] 発達障害と不安、強迫、トラウマ：そのかさなるとつらなり (2019)
  • Author(s): 岡田俊
  • Organizer: 第11回日本不安症学会
  • Invited
• [Presentation] 発達障害のある子の育ちと育みを支えるということ (2019)
  • Author(s): 岡田俊
  • Organizer: 第177回東海精神神経学会総会
  • Invited
• [Presentation] 神経発達症の子どもの育ちのあゆみと育み (2017)
  • Author(s): 岡田 俊
  • Organizer: 第１１３回日本精神神経学会学術総会
• [Presentation] 自閉スペクトラム症の易刺激性と薬物療法 (2016)
  • Author(s): 岡田俊
  • Organizer: 第26回日本臨床精神神経薬理学会
  • Place of Presentation: ホルトホール大分（大分県大分市）
  • Year and Date: 2016-11-17
  • Invited
• [Presentation] 自閉症スペクトラムと薬物療法 (2016)
  • Author(s): 岡田俊
  • Organizer: 第51回日本発達障害学会
  • Place of Presentation: 京都教育大学（京都府京都市）
  • Year and Date: 2016-08-27
  • Invited
• [Book] 2020年版 発達障害白書 (2019)
  • Author(s): 日本発達障害連盟 編 岡田俊ほか
  • Total Pages: 200
  • Publisher: 明石書店
  • ISBN: 9784750348896
• [Book] こころの治療薬ハンドブック第12版 (2019)
  • Author(s): 井上猛、桑原斉、酒井隆、鈴木映二、水上勝義、宮田久嗣、諸川由実代、吉尾隆、渡邉博幸 編 岡田 俊ほか
  • Total Pages: 428
  • Publisher: 星和書店
  • ISBN: 4791110048
• [Book] 精神科薬物療法マニュアル (2018)
  • Author(s): 木平健治、山田清文、天正雅美、岡田俊ほか
  • Total Pages: 326
  • Publisher: 南山堂
  • ISBN: 9784525773915
• [Book] 発達障害白書2019年版 (2018)
  • Author(s): 會田千重、朝日雅也、阿部達也、岡田俊ほか
  • Total Pages: 200
  • Publisher: 明石書店
  • ISBN: 9784750347202
• [Book] 児童・青年期精神疾患の薬物治療ガイドライン (2018)
  • Author(s): 中村和彦、飯田順三、石飛信、岡田俊ほか
  • Total Pages: 380
  • Publisher: じほう
  • ISBN: 9784840751124
• [Book] 今日の治療指針Vol.60 (2018)
  • Author(s): 福井次矢、高木誠、小室一成、岡田俊ほか
  • Total Pages: 2066
  • Publisher: 医学書院
  • ISBN: 9784260032346
• [Book] 子ども・大人の発達障害診療ハンドブック (2018)
  • Author(s): 内山登紀夫、宇野洋太、蜂矢百合子、岡田俊ほか
  • Total Pages: 314
  • Publisher: 中山書店
  • ISBN: 9784521745688
• [Book] こころの医学入門 (2017)
  • Author(s): 近藤直司、田中康雄、本田秀夫、岡田俊ほか
  • Total Pages: 330
  • Publisher: 中央法規
  • ISBN: 9784805854952
• [Book] 発達障害白書２０１８年度版 (2017)
  • Author(s): 熊谷晋一郎、田中哲、平田勝政、岡田俊ほか
  • Total Pages: 200
  • Publisher: 明石書店
  • ISBN: 9784750345680
• [Book] 臨床児童精神医学ハンドブック (2016)
  • Author(s): 本城秀次、野邑健二、岡田俊（編）
  • Total Pages: 544
  • Publisher: 西村書店
• [Book] 明石書店 (2016)
  • Author(s): 日本発達障害連盟（編）
  • Total Pages: 216
  • Publisher: 発達障害白書2017年版