Comparison of the cerebral function before and after the oxytocin administration for patients with autism spectrum disorder.

• Project/Area Number: 24390282
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Kanazawa University
• Principal Investigator: MINABE Yoshio 金沢大学, 医学系, 教授 (60181947)
• Co-Investigator(Kenkyū-buntansha): MUNESUE Toshio 金沢大学, 子どものこころの発達研究センター, 特任教授 (50293353) ; KIKUCHI Mitsuru 金沢大学, 子どものこころの発達研究センター, 特任教授 (00377384) ; OUCHI Yasuomi 浜松医科大学, 分子イメージング先端研究センター, 教授 (40436978)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000); Fiscal Year 2014: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2012: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
• Keywords: オキシトシン / 自閉症スペクトラム / セロトニン / PET / 自閉症スペクトラム障害 / MEG / 脳画像研究 / セロトニン系システム / 広汎性発達障害 / 遺伝子研究 / GABA系ニューロン

Outline of Final Research Achievements

With chronic administration of the oxytocin to the patients with autism spectrum disorder who does not have intelligence impairment, we investigated the influence on the serotonin system and the influence on a social cognitive function. The neurophysiological characterization of the patient who improves with oxytocin administration was also explored. We investigated the changes of the serotonin transporter density after the drug treatment (ten weeks), and we also investigated the changes in brain response to social stimuli recorded by MEG. Study desing: Non-randomized, open and uncontrolled.

Research Products

• [Journal Article] Attentional control and interpretation of facial expression after oxytocin administration to typically developed male adults. (2015)
  • Author(s): Hirosawa T, Kikuchi M, Okumura E, Yoshimura Y, Hiraishi H, Munesue T, Takesaki N, Furutani N, Ono Y, Higashida H, Minabe Y
  • Journal Title: PLoS One Volume: 6 Issue: 2 Pages: e0116918-e0116918
  • DOI: 10.1371/journal.pone.0116918
  • Peer Reviewed / Open Access
• [Journal Article] Reduced long-range functional connectivity in young children with autism spectrum disorder. (2015)
  • Author(s): Kikuchi M, Yoshimura Y, Hiraishi H, Munesue T, Hashimoto T, Tsubokawa T, Takahashi T, Suzuki M, Higashida H, Minabe Y.
  • Journal Title: Soc Cogn Affect Neurosci. Volume: 10 Issue: 2 Pages: 248-254
  • DOI: 10.1093/scan/nsu049
  • Peer Reviewed / Open Access
• [Journal Article] Unusual developmental pattern of brain lateralization in young boys with autism spectrum disorder: Power analysis with child-sized magnetoencephalography. (2015)
  • Author(s): Hiraishi H, Kikuchi M, Yoshimura Y, Kitagawa S, Hasegawa C, Munesue T, Takesaki N, Ono Y, Takahashi T, Suzuki M, Higashida H, Asada M, Minabe Y.
  • Journal Title: Psychiatry Clin Neurosci Volume: 69 Issue: 3 Pages: 153-160
  • DOI: 10.1111/pcn.12261
  • Peer Reviewed
• [Journal Article] Broader autism phenotype in mothers predicts social responsiveness in young children with autism spectrum disorders. (2015)
  • Author(s): Hasegawa C, Kikuchi M, Yoshimura Y, Hiraishi H, Munesue T, Nakatani H, Higashida H, Asada M, Oi M, Minabe Y.
  • Journal Title: Psychiatry Clin Neurosci Volume: 69 Issue: 3 Pages: 136-144
  • DOI: 10.1111/pcn.12210
  • Peer Reviewed
• [Journal Article] Utility of Scalp Hair Follicles as a Novel Source of Biomarker Genes for Psychiatric Illnesses. (2014)
  • Author(s): Maekawa M, Yamada K, Toyoshima M, Ohnishi T, Iwayama Y, Shimamoto C, Toyota T, Nozaki Y, Balan S, Matsuzaki H, Iwata Y, Suzuki K, Miyashita M, Kikuchi M, Kato M, Okada Y, Akamatsu W, Mori N, Owada Y, Itokawa M, Okano H, Yoshikawa T.
  • Journal Title: Biological Psychiatry Volume: 3223 Issue: 2 Pages: 00570-00578
  • DOI: 10.1016/j.biopsych.2014.07.025
  • NAID: 40020643113
  • Peer Reviewed / Open Access
• [Journal Article] A longitudinal study of auditory evoked field and language development in young children (2014)
  • Author(s): Yoshimura Yuko, Kikuchi Mitsuru, Ueno Sanae, Shitamichi Kiyomi, Remijn Gerard, Hiraishi Hirotoshi, Hasegawa Chiaki, Furutani Naoki, Oi Manabu, Munesue Toshio, Tsubokawa Tunehisa, Higashida Haruhiro, Minabe Yoshio
  • Journal Title: NeuroImage Volume: 1;101 Pages: 440-447
  • DOI: 10.1016/j.neuroimage.2014.07.034
  • Peer Reviewed / Open Access
• [Journal Article] Somatosensory evoked field in response to visuotactile stimulation in 3- to 4-year-old children. (2014)
  • Author(s): Remijn GB, Kikuchi M, Shitamichi K, Ueno S, Yoshimura Y, Nagao K, Tsubokawa T, Kojima H, Higashida H, Minabe Y.
  • Journal Title: Front Hum Neurosci Volume: 24 Pages: 170-170
  • DOI: 10.3389/fnhum.2014.00170
  • Peer Reviewed / Open Access
• [Journal Article] Lower gene expression for KCNS3 potassium channel subunit in parvalbumin-containing neurons in the prefrontal cortex in schizophrenia. (2014)
  • Author(s): Georgiev D, Arion D, Enwright JF, Kikuchi M, Minabe Y, Corradi JP, Lewis DA, Hashimoto T.
  • Journal Title: Am J Psychiatry. Volume: 171 Pages: 62-71
  • Peer Reviewed
• [Journal Article] Relationship between brain network pattern and cognitive performance of children revealed by MEG signals during free viewing of video. (2014)
  • Author(s): Duan F, Watanabe K, Yoshimura Y, Kikuchi M, Minabe Y, Aihara K.
  • Journal Title: Brain Cogn Volume: 86 Pages: 10-16
  • DOI: 10.1016/j.bandc.2014.01.011
  • Peer Reviewed
• [Journal Article] Lower gene expression for KCNS3 potassium channel subunit in parvalbumin-containing neurons in the prefrontal cortex in schizophrenia. (2014)
  • Author(s): Georgiev D
  • Journal Title: Am J Psychiatry Volume: 1 Issue: 1 Pages: 62-71
  • DOI: 10.1176/appi.ajp.2013.13040468
  • Peer Reviewed
• [Journal Article] Altered brain connectivity in 3-to-7-year-old children with autism spectrum disorder. (2013)
  • Author(s): Kikuchi, M., Shitamichi, K., Yoshimura, Y., Ueno, S., et al., Remijn, G.B., Takahashi, T., Suzuki, M., Higashida, H., Minabe, Y.
  • Journal Title: Neuroimage: Clinical Volume: 2 Pages: 394-401
  • DOI: 10.1016/j.nicl.2013.03.003
  • Peer Reviewed
• [Journal Article] The brain's response to the human voice depends on the incidence of autistic traits in the general population (2013)
  • Author(s): Y Yoshimura, M Kikuchi, S Ueno, E Okumura, H Hiraishi, C Hasegawa, G B Remijn, K Shitamichi, T Munesue, T Tsubokawa, H Higashida, Y Minabe
  • Journal Title: PLoS One Volume: 20巻 Issue: 11 Pages: e80126-e80126
  • DOI: 10.1371/journal.pone.0080126
  • Peer Reviewed
• [Journal Article] Atypical brain lateralisation in the auditory cortex and language performance in 3- to 7-year-old children with high-functioning autism spectrum disorder : a child-customised magnetoencephalography (MEG) study (2013)
  • Author(s): Y Yoshimura, M Kikuchi, K Shitamichi, S Ueno, T Munesue, Y Ono, T Tsubokawa, Y Haruta, M Oi, Y Niida, GB Remijn, T Takahashi, M Suzuki, H Higashida, Y Minabe
  • Journal Title: Mol Autism Volume: 8巻 Issue: 1 Pages: 38-38
  • DOI: 10.1186/2040-2392-4-38
  • Peer Reviewed
• [Journal Article] Anterior prefrontal hemodynamic connectivity in conscious 3- to 7-year-old children with typical development and autism spectrum disorder. (2013)
  • Author(s): Kikuchi, M., Yoshimura, Y., Shitamichi, K., Ueno, S., et al., Remijn, G.B., Takahashi, T., Suzuki, M., Higashida, H., Minabe, Y.
  • Journal Title: PloSONE Volume: 8 Issue: 2 Pages: 56087-56087
  • DOI: 10.1371/journal.pone.0056087
  • Peer Reviewed
• [Journal Article] A custom magnetoencephalography device reveals brain connectivity and high reading/decoding ability in children with autism. (2013)
  • Author(s): Kikuchi M.
  • Journal Title: Scientific Reports Volume: 3 Pages: 1139-1139
  • NAID: 120005821068
  • Peer Reviewed
• [Journal Article] Spatiotemporal frequency characteristics of cerebral oscillations during the perception of fundamental frequency contour changes in one-syllable intonation (2012)
  • Author(s): Ueno S, Okumura E, Remijn GB, YoshimuraY, Kikuchi M, Shitamichi K, Nagao K, Mochiduki M, Haruta Y, Hayashi N, Munesue T, Tsubokawa T, Oi M, NakataniH, Higashida H, MinabeY.
  • Journal Title: Neurosci Lett Volume: (in press) Issue: 2 Pages: 141-146
  • DOI: 10.1016/j.neulet.2012.03.031
  • Peer Reviewed
• [Journal Article] Oxytocin attenuates feelings of hostility depending on emotional context and individuals' characteristics (2012)
  • Author(s): Tetsu Hirosawa1, Mitsuru Kikuchi, Haruhiro Higashida, Eiichi Okumura, Sanae Ueno, Kiyomi Shitamichi, YukoYoshimura, Toshio Munesue, TsunehisaTsubokawa, Yasuhiro Haruta, Hideo Nakatani, Takanori Hashimoto, Yoshio Minabe
  • Journal Title: Scientific Reports Volume: (in press) Issue: 1 Pages: 384-384
  • DOI: 10.1038/srep00384
  • NAID: 120005821069
  • Peer Reviewed
• [Journal Article] Lateralized theta wave connectivity and language performance in 2- to 5-old children (2012)
  • Author(s): 三邉義雄
  • Journal Title: 子どものこころと脳の発達 Volume: 3 Pages: 52-53
  • Peer Reviewed
• [Journal Article] 自閉症スペクトラム障害を対象としたオキシトシン臨床試験の国内外での状況 (2012)
  • Author(s): 芦村和美
  • Journal Title: 北陸神経精神医学雑誌 Volume: 26 Pages: 37-39
  • Peer Reviewed
• [Journal Article] Social memory, amnesia, and autism : brain oxytocin secretion is regulated by NAD+ and single nucleotide polymorphism of CD38 (2012)
  • Author(s): Higashida, H
  • Journal Title: Neurochem Int Volume: (in press) Issue: 6 Pages: 828-838
  • DOI: 10.1016/j.neuint.2012.01.030
  • Peer Reviewed
• [Presentation] 自閉症スペクトラム障害の認知特性と脳機能の特徴 (2014)
  • Author(s): 菊知 充
  • Organizer: 第14回、「精神疾患と認知機能研究会」
  • Place of Presentation: 海運クラブ（東京都）
  • Year and Date: 2014-11-08
• [Presentation] Neuroimaging for brain development in young children (2014)
  • Author(s): 菊知 充、三邉義雄
  • Organizer: 第4回 賀戸久先生記念研究会
  • Place of Presentation: TOKYO REIT虎ノ門ビル（東京都）
  • Year and Date: 2014-11-07
  • Invited
• [Presentation] 広汎性発達障害の早期診断のための診断システム開発, (2014)
  • Author(s): 菊知 充
  • Organizer: 第45回公益財団法人アステラス病態代謝研究会
  • Place of Presentation: 日本工業倶楽部（東京都）
  • Year and Date: 2014-10-18
• [Presentation] 子どものこころの生物学 (2014)
  • Author(s): 三邉義雄
  • Organizer: 第１回大阪大学COIワークショップ
  • Place of Presentation: 大阪大学中ノ島センター10F
• [Presentation] 自閉症スペクトラム障害の幼児期における脳機能結合低下：MEG長距離センサー間の検討 (2013)
  • Author(s): 三邉義雄
  • Organizer: 第４０回日本脳科学会
  • Place of Presentation: アクトシティ浜松 コングレスセンター(浜松市）
• [Presentation] 脳科学から見た発達障がいと音楽 (2013)
  • Author(s): 菊知充
  • Organizer: ミュージックケア学会
  • Place of Presentation: 加佐ノ岬倶楽部 （加賀市）
  • Invited
• [Presentation] 招待シンポジウム：発達障害児の行動をもっと理解する：最先端の脳科学研究から (2013)
  • Author(s): 菊知充
  • Organizer: 独立行政法人 国立精神・神経医療研究センター
  • Place of Presentation: イイノホール(東京）
  • Invited
• [Presentation] 自閉症スペクトラム障害児の理解を目指して：脳科学研究から (2013)
  • Author(s): 菊知充
  • Organizer: 第3回福井県精神科治療研究会
  • Place of Presentation: バードグリーンホテル（福井市）
  • Invited
• [Presentation] Brain connectivity in young children with autism (2013)
  • Author(s): 菊知充
  • Organizer: International Society for the Advancement of Clinical Magnetoencephalography meeting 2013
  • Place of Presentation: Tokyo Dome Hotel Sapporo （札幌市）
• [Presentation] 自閉症スペクトラム障害幼児期における、脳機能結合低下と認知特性 (2013)
  • Author(s): 菊知充
  • Organizer: 第46回 精神神経系薬物治療研究報告会
  • Place of Presentation: 千里ライフサイエンスセンター（大阪府豊中市）
  • Invited
• [Presentation] シンポジウム：幼児用MEGをもちいた広汎性発達障害の脳機能評価 (2013)
  • Author(s): 菊知充
  • Organizer: 第28回日本生体磁気学会
  • Place of Presentation: 朱鷺メッセ（新潟県新潟市）
• [Presentation] Brain connectivity and high reading/decoding ability in young children with autism. (2013)
  • Author(s): Mitsuru Kikuchi
  • Organizer: Neuro2013
  • Place of Presentation: 国立京都国際会館 （京都市）
• [Presentation] An approach with a new neuroimaging methods for young children. (2013)
  • Author(s): Mitsuru Kikuchi
  • Organizer: IEEE ICDL-EpiRob2013 Special Session
  • Place of Presentation: Oosaka Central Public Hall （大阪市）
• [Presentation] A novel method of creating a brain template for mapping in MEG without the need of an MRI (2012)
  • Author(s): Hachiman Y.
  • Organizer: Radiological Society of North America 2012 98th Scientific Assembly and Annual Meeting
  • Place of Presentation: McCormick Place(米)
  • Year and Date: 2012-11-26
• [Presentation] Toward Diagnosis and Therapy of Autism: MEG and Oxytocin (2012)
  • Author(s): Minabe Y
  • Organizer: Japan-Korea Joint symposium
  • Place of Presentation: 金沢大学医学部記念館(石川県)
  • Year and Date: 2012-11-07
• [Presentation] 発達障害の早期発見に向けた研究 (2012)
  • Author(s): 菊知充
  • Organizer: 第47回北陸心理学会
  • Place of Presentation: 金沢大学サテライト・プラザ(石川県)(招待講演)
  • Year and Date: 2012-10-27
• [Presentation] 未就学広汎性発達障害児の認知機能および脳機能結合の特性 (2012)
  • Author(s): 菊知充
  • Organizer: 第21回海馬と高次脳機能学会
  • Place of Presentation: 湯涌創作の森(石川県)
  • Year and Date: 2012-10-07
• [Presentation] 未就学広汎性発達障害児の大脳半球側性化:幼児用MEGによる検討 (2012)
  • Author(s): 三邉義雄
  • Organizer: 第39回日本脳科学会
  • Place of Presentation: リーガロイヤルホテル小倉(福岡県)
  • Year and Date: 2012-10-04
• [Presentation] MEGによる定型発達児と自閉症児の自発脳活動の比較 (2012)
  • Author(s): 平石博敏
  • Organizer: 第39回日本脳科学会
  • Place of Presentation: リーガロイヤルホテル小倉(福岡県)
  • Year and Date: 2012-10-04
• [Presentation] 小児MEG検査におけるマツピング用MR画像作成手法に関する研究:テンプレート選択手法の最適化 (2012)
  • Author(s): 八幡優希
  • Organizer: 第40回日本放射線技術学会秋季学術大会
  • Place of Presentation: タワーホール船堀(東京都)
  • Year and Date: 2012-10-04
• [Presentation] 幼児用MEGによる未就学広汎性発達障害児の生理学的検討 (2012)
  • Author(s): 三邉義雄
  • Organizer: 第34回日本生物学的精神医学会
  • Place of Presentation: 神戸国際会議(兵庫県)
  • Year and Date: 2012-09-30
• [Presentation] 幼児の脳機能測定 (2012)
  • Author(s): 菊知充
  • Organizer: 神経ダイナミクスから社会的相互作用へ至る過程の理解と構築による構成的発達科学研究会
  • Place of Presentation: 大阪大学(大阪府)(招待講演)
  • Year and Date: 2012-09-28
• [Presentation] Oxytocin attenuates feelings of hostility depending on emotional context and individuals? characteristics. (2012)
  • Author(s): Hirosawa Tetsu
  • Organizer: 18th International Conference on Biomagnetism
  • Place of Presentation: MAISON DE LA CHIMIE (仏)
  • Year and Date: 2012-08-27
• [Presentation] MEG-NIRS統合機の開発:幼児への応用 (2012)
  • Author(s): 菊知充
  • Organizer: 第14回ヒト脳機能マッピング学会
  • Place of Presentation: 京王プラザホテル札幌(北海道)(招待講演)
  • Year and Date: 2012-07-06
• [Presentation] 幼児の言語発達と脳機能結合:コピーレンズ解析による試み (2012)
  • Author(s): 菊知充
  • Organizer: 第27回 日本生体磁気学会大会
  • Place of Presentation: 東京電機大学(東京都)
  • Year and Date: 2012-05-31
• [Remarks] 子どものこころの発達研究センター
  • URL: http://kodomokokoro.w3.kanazawa-u.ac.jp/
• [Remarks] 金沢大学附属病院神経科精神科
  • URL: http://psychiatry.w3.kanazawa-u.ac.jp/
• [Remarks] バンビプラン
  • URL: http://bambiplan.w3.kanazawa-u.ac.jp/
• [Remarks] 連合小児発達学研究科 金沢校
  • URL: http://rengou.w3.kanazawa-u.ac.jp/