Reconsideration of the diagnostic system for neurodevelopmental disorders with a focus on functional impairment

2022 Fiscal Year Annual Research Report

• Project/Area Number: 22H00492
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: 土屋 賢治 浜松医科大学, 子どものこころの発達研究センター, 特任教授 (20362189)
• Co-Investigator(Kenkyū-buntansha): 友田 明美 福井大学, 子どものこころの発達研究センター, 教授 (80244135) ; 伊東 宏晃 浜松医科大学, 医学部, 教授 (70263085) ; 原 武史 岐阜大学, 工学部, 教授 (10283285) ; 松崎 秀夫 福井大学, 子どものこころの発達研究センター, 教授 (00334970) ; 戸田 重誠 昭和大学, 医学部, 准教授 (00323006) ; 高橋 長秀 名古屋大学, 医学部附属病院, 准教授 (50846714) ; 大島 郁葉 千葉大学, 子どものこころの発達教育研究センター, 教授 (40625472) ; 西村 倫子 浜松医科大学, 子どものこころの発達研究センター, 特任講師 (30773791)
• Project Period (FY): 2022-04-01 – 2025-03-31
• Keywords: 発達障がい / 機能障がい / 自閉スペクトラム症 / 注意欠如多動症 / 出生コホート

Outline of Annual Research Achievements

本研究の目的は、神経発達症に伴う機能障がいの生物学的および社会心理学的基盤を探索し、神経発達症の診断体系を再構成することである。具体的には、浜松母と子の出生コホートを用いて、乳幼児期の社会・コミュニケーション・日常生活機能の変遷と、その神経発達症の診断閾値に与える影響を検討した（Nishimura et al., Psychiatr Clin Neurosci 2023）。また、幼少期のデジタル曝露と外遊びがのちの機能障害の形成に影響を与える可能性が示された（Sugiyama et al, JAMA Pediatr 2023）。さらに、虐待などの不適切な養育「マルトリートメント」を受けて反応性愛着障害を発症した子どもを対象に、オキシトシン経鼻投与による神経報酬処理への影響を解明し、同障害の病態解明および病態特徴に基づく治療薬開発など、臨床応用への発展に貢献した（Takiguchi et al，Front Child Adolesc Psychiatr 2023）。また、臍帯血中のエポキシ脂肪酸の測定により、臍帯血中のリノール酸とリノール酸由来のジオール・ジヒドロキシオクタデセン酸が低出生体重と有意に負の相関があることが見出された（Umeda et al, Front Endocrinol 2022）。さらに、胎盤病理所見、特に母体側の血管還流不全と胎児側の絨毛成熟の遅延は、児の神経発達の遅延に関連していた（Ueda et al., Sci Rep 2022）。最後に、成人ADHD患者瞳孔径のベースラインにおける左右差について定型発達者（TD）とADHD患者群で複雑性解析を行い、ADHD群でより右側にて有意な複雑性を認めた（Kumano et al, Neural Comput 2022）。これらの研究結果は、神経発達症の理解に新たな視点を提供している。

Current Status of Research Progress

1: Research has progressed more than it was originally planned.

Reason

出生コホートを用いた研究で，当初の想定以上にデータ解析と論文執筆が進捗し，大きな成果をあげることができた。

Strategy for Future Research Activity

前年度同様に当初の研究計画に沿った実施を行う。とくに，出世コホート研究では，視線計測を用いた機能障がい指標の探索に力点をおく。

Research Products

• [Int'l Joint Research] ニューヨーク市立大/マウントサイナイ大学(米国)
  • Country Name: U.S.A.
  • Counterpart Institution: ニューヨーク市立大/マウントサイナイ大学
• [Journal Article] Identifying Active Progeny Virus Particles in Formalin-Fixed, Paraffin-Embedded Sections Using Correlative Light and Scanning Electron Microscopy (2023)
  • Author(s): Itoh Toshiya、Yamada Satoshi、Ohta Isao、Meguro Shiori、Kosugi Isao、Iwashita Toshihide、Itoh Hiroaki、Kanayama Naohiro、Okudela Koji、Sugimura Haruhiko、Misawa Kiyoshi、Hariyama Takahiko、Kawasaki Hideya
  • Journal Title: Laboratory Investigation Volume: 103 Pages: 100020～100020
  • DOI: 10.1016/j.labinv.2022.100020
  • Peer Reviewed / Open Access
• [Journal Article] Outdoor Play as a Mitigating Factor in the Association Between Screen Time for Young Children and Neurodevelopmental Outcomes (2023)
  • Author(s): Sugiyama M, Tsuchiya KJ, Okubo Y, Rahman MS, Uchiyama S, Harada T, Iwabuchi T, Okumura A, Nakayasu C, Amma Y, Suzuki H, Takahashi N, Kinsella-Kammerer B, Nomura Y, Itoh H, Nishimura T
  • Journal Title: JAMA Pediatrics Volume: 177 Pages: 303～303
  • DOI: 10.1001/jamapediatrics.2022.5356
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Impact of stable environments on maltreated children (2023)
  • Author(s): Koizumi Michiko、Tomoda Akemi、Takiguchi Shinichiro、Kosaka Hirotaka
  • Journal Title: Pediatrics International Volume: 65 Pages: e15443
  • DOI: 10.1111/ped.15443
  • Peer Reviewed / Open Access
• [Journal Article] Effects of intranasal oxytocin on neural reward processing in children and adolescents with reactive attachment disorder: A randomized controlled trial (2023)
  • Author(s): Takiguchi Shinichiro、Makita Kai、Fujisawa Takashi X.、Nishitani Shota、Tomoda Akemi
  • Journal Title: Frontiers in Child and Adolescent Psychiatry Volume: 1 Pages: 1056115
  • DOI: 10.3389/frcha.2022.1056115
  • Peer Reviewed
• [Journal Article] Effects of prenatal cannabis exposure on developmental trajectory of cognitive ability and brain volumes in the adolescent brain cognitive development (ABCD) study (2023)
  • Author(s): Hiraoka Daiki、Makita Kai、Hamatani Sayo、Tomoda Akemi、Mizuno Yoshifumi
  • Journal Title: Developmental Cognitive Neuroscience Volume: 60 Pages: 101209
  • DOI: 10.1016/j.dcn.2023.101209
  • Peer Reviewed / Open Access
• [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 Shota、Isozaki Makoto、Yao Akiko、Higashino Yoshifumi、Yamauchi Takahiro、Kidoguchi Masamune、Kawajiri Satoshi、Tsunetoshi Kenzo、Neish Hiroyuki、Imoto Hirochika、Arishima Hidetaka、Kodera Toshiaki、Fujisawa Takashi X.、Nomura Sadahiro、Kikuta Kenichiro、Shinozaki Gen、Tomoda Akemi
  • Journal Title: Translational Psychiatry Volume: 13 Pages: 72
  • DOI: 10.1038/s41398-023-02370-0
  • Peer Reviewed / Open Access
• [Journal Article] Neural mechanisms underlying rule selection based on response evaluation: a near-infrared spectroscopy study (2022)
  • Author(s): Harada T, Iwabuchi T, Senju A, Nakayasu C, Nakahara R, Tsuchiya KJ, Hoshi Y
  • Journal Title: Sci Rep Volume: 12 Pages: 20696
  • DOI: 10.1038/s41598-022-25185-3
  • Peer Reviewed / Open Access
• [Journal Article] Early temperament as a predictor of language skills at 40 months (2022)
  • Author(s): Ishikawa-Omori Y, Nishimura T, Nakagawa A, Okumura A, Harada T, Nakayasu C, Iwabuchi T, Amma Y, Suzuki H, Rahman MS, Nakahara R, Takahashi N, Nomura Y, Tsuchiya KJ
  • Journal Title: BMC Pediatrics Volume: 22 Pages: 56
  • DOI: 10.1186/s12887-022-03116-5
  • Peer Reviewed / Open Access
• [Journal Article] Associations Among Maternal Metabolic Conditions, Cord Serum Leptin Levels, and Autistic Symptoms in Children (2022)
  • Author(s): Iwabuchi T, Takahashi N, Nishimura T, Rahman MS, Harada T, Okumura A, Kuwabara H, Takagai S, Nomura Y, Matsuzaki H, Ozaki N, Tsuchiya KJ
  • Journal Title: Frontiers in Psychiatry Volume: 12 Pages: 816196
  • DOI: 10.3389/fpsyt.2021.816196
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Identification of neurodevelopmental transition patterns from infancy to early childhood and risk factors predicting descending transition (2022)
  • Author(s): Kato T, Nishimura T, Takahashi N, Harada T, Okumura A, Iwabuchi T, Nomura Y, Senju A, Tsuchiya KJ, Takei N
  • Journal Title: Scientific Reports Volume: 12 Pages: 4822
  • DOI: 10.1038/s41598-022-08827-4
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Trajectories of Adaptive Behaviors During Childhood in Females and Males in the General Population (2022)
  • Author(s): Nishimura T, Kato T, Okumura A, Harada T, Iwabuchi T, Rahman MS, Hiroya T, Takahashi M, Adachi M, Kuwabara H, Takagai S, Nomura Y, Takahashi N, Senju A, Tsuchiya KJ. Trajectories of adaptive behaviors during childhood in females and males in the general population
  • Journal Title: Frontiers in Psychiatry Volume: 13 Pages: 817383
  • DOI: 10.3389/fpsyt.2022.817383
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Placental pathology predicts infantile neurodevelopment (2022)
  • Author(s): Ueda M, Tsuchiya KJ, Yaguchi C, Furuta-Isomura N, Horikoshi Y, Matsumoto M, Suzuki M, Oda T, Kawai K, Itoh T, Matsuya M, Narumi M, Kohmura-Kobayashi Y, Tamura N, Uchida T, Itoh H
  • Journal Title: Scientific Reports Volume: 12 Pages: 2578
  • DOI: 10.1038/s41598-022-06300-w
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Linoleic acid and linoleate diols in neonatal cord blood influence birth weight (2022)
  • Author(s): Umeda N, Hirai T, Ohto-Nakanishi T, Tsuchiya KJ, Matsuzaki H
  • Journal Title: Frontiers in Endocrinology Volume: 13 Pages: -
  • DOI: 10.3389/fendo.2022.986650
  • Peer Reviewed / Open Access
• [Journal Article] Maternal Plasma and Cord Blood Concentration Profiles of Duloxetine During the Peripartum Period and Their Associations With the Modified Finnegan Score (2022)
  • Author(s): Taguchi Reina、Naito Takafumi、Suzuki Koji、Kurosawa Yuko、Itoh Hiroaki、Kawakami Junichi
  • Journal Title: Therapeutic Drug Monitoring Volume: 44 Pages: 351～352
  • DOI: 10.1097/FTD.0000000000000943
  • Peer Reviewed
• [Journal Article] Comparative Analysis of Gene Expression Profiles in the Adipose Tissue of Obese Adult Mice With Rapid Infantile Growth After Undernourishment In Utero (2022)
  • Author(s): Suzuki Misako、Kohmura-Kobayashi Yukiko、Ueda Megumi、Furuta-Isomura Naomi、Matsumoto Masako、Oda Tomoaki、Kawai Kenta、Itoh Toshiya、Matsuya Madoka、Narumi Megumi、Tamura Naoaki、Uchida Toshiyuki、Mochizuki Kazuki、Itoh Hiroaki
  • Journal Title: Frontiers in Endocrinology Volume: 13 Pages: 818064
  • DOI: 10.3389/fendo.2022.818064
  • Peer Reviewed / Open Access
• [Journal Article] Intrauterine Hyponutrition Reduces Fetal Testosterone Production and Postnatal Sperm Count in the Mouse (2022)
  • Author(s): Fujisawa Yasuko、Ono Hiroyuki、Konno Alu、Yao Ikuko、Itoh Hiroaki、Baba Takashi、Morohashi Kenichirou、Katoh-Fukui Yuko、Miyado Mami、Fukami Maki、Ogata Tsutomu
  • Journal Title: Journal of the Endocrine Society Volume: 6 Pages: bvac022
  • DOI: 10.1210/jendso/bvac022
  • Peer Reviewed
• [Journal Article] Developmental Origins of Metaflammation; A Bridge to the Future Between the DOHaD Theory and Evolutionary Biology (2022)
  • Author(s): Itoh Hiroaki、Ueda Megumi、Suzuki Misako、Kohmura-Kobayashi Yukiko
  • Journal Title: Frontiers in Endocrinology Volume: 13 Pages: 839436
  • DOI: 10.3389/fendo.2022.839436
  • Peer Reviewed / Open Access
• [Journal Article] Pregnancy complicated by neurofibromatosis type 1 in a patient with a history of massive spontaneous hemothorax: a case report (2022)
  • Author(s): Kitamoto Mei、Narumi Megumi、Oda Tomoaki、Tamura Naoaki、Uchida Toshiyuki、Itoh Hiroaki
  • Journal Title: Hypertension Research in Pregnancy Volume: 10 Pages: 121～124
  • DOI: 10.14390/jsshp.HRP2022-006
  • Peer Reviewed
• [Journal Article] Editorial: A Half-Century History of Nutritional Guidance for Pregnant Women in Japan: A Promising Research Target of the DOHaD Study (2022)
  • Author(s): Itoh Hiroaki、Aoyama Tomoko、Kohmura-Kobayashi Yukiko、Nemoto Takahiro
  • Journal Title: Frontiers in Endocrinology Volume: 13 Pages: 942256
  • DOI: 10.3389/fendo.2022.942256
  • Peer Reviewed / Open Access
• [Journal Article] The Effectiveness and Cost-effectiveness of Well Parent Japan for Japanese Mothers of Children With ADHD: Protocol for a Randomized Controlled Trial (2022)
  • Author(s): Shimabukuro Shizuka、Daley David、Endo Takahiro、Harada Satoshi、Tomoda Akemi、Yamashita Yushiro、Oshio Takashi、Guo Boliang、Ishii Atsuko、Izumi Mio、Nakahara Yukiko、Yamamoto Kazushi、Yao Akiko、Tripp Gail
  • Journal Title: JMIR Research Protocols Volume: 11 Pages: e32693
  • DOI: 10.2196/32693
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Beneficial Effects of Behavioral Parent Training on Inhibitory Control in Children With Attention-Deficit/Hyperactivity Disorder: A Small-Scale Randomized Controlled Trial (2022)
  • Author(s): Yao Akiko、Shimada Koji、Kasaba Ryoko、Tomoda Akemi
  • Journal Title: Frontiers in Psychiatry Volume: 13 Pages: 859249
  • DOI: 10.3389/fpsyt.2022.859249
  • Peer Reviewed / Open Access
• [Journal Article] The influence of intelligence and cognitive abilities on the reading ability of Japanese students with developmental disorders (2022)
  • Author(s): Yamaguchi Daisuke、Hiratani Michio、Matsuura Naomi、Fujisawa Takashi X.、Takiguchi Shinichiro、Fujioka Toru、Kono Toshihiro、Ishizaka Ikuyo、Tomoda Akemi
  • Journal Title: Brain and Development Volume: 44 Pages: 361-371
  • DOI: 10.1016/j.braindev.2022.02.006
  • Peer Reviewed
• [Journal Article] Guided internet-based cognitive behavioral therapy for obsessive-compulsive disorder: A multicenter randomized controlled trial in Japan (2022)
  • Author(s): Matsumoto Kazuki、Hamatani Sayo、Makino Takuya、Takahashi Jumpei、Suzuki Futoshi、Ida Tomoko、Hamamura Shoko、Takiguchi Shinichiro、Tomoda Akemi、Omori Ichiro M.、Kosaka Hirotaka、Shinno Seina、Ikai Tomoki、Hayashi Hiroyuki、Katayama Hiroto、Shiko Yuki、Ozawa Yoshihito、Kawasaki Yohei、Sutoh Chihiro、Shimizu Eiji
  • Journal Title: Internet Interventions Volume: 28 Pages: 100515
  • DOI: 10.1016/j.invent.2022.100515
  • Peer Reviewed / Open Access
• [Journal Article] Methylphenidate remediates aberrant brain network dynamics in children with attention‐deficit/hyperactivity disorder: A randomized controlled trial (2022)
  • Author(s): Mizuno Yoshifumi、Cai Weidong、Supekar Kaustubh、Makita Kai、Takiguchi Shinichiro、Tomoda Akemi、Menon Vinod
  • Journal Title: NeuroImage Volume: 257 Pages: 119332
  • DOI: 10.1016/j.neuroimage.2022.119332
  • Peer Reviewed / Open Access
• [Journal Article] Longitudinal impact of COVID-19 pandemic on mental health of children in the ABCD study cohort (2022)
  • Author(s): Hamatani Sayo、Hiraoka Daiki、Makita Kai、Tomoda Akemi、Mizuno Yoshifumi
  • Journal Title: Scientific Reports Volume: 12 Pages: -
  • DOI: 10.1038/s41598-022-22694-z
  • Peer Reviewed / Open Access
• [Journal Article] Phldb2 is essential for regulating hippocampal dendritic spine morphology through drebrin in an adult-type isoform-specific manner (2022)
  • Author(s): Xie Min-Jue、Yagi Hideshi、Iguchi Tokuichi、Yamazaki Hiroyuki、Hanamura Kenji、Matsuzaki Hideo、Shirao Tomoaki、Sato Makoto
  • Journal Title: Neuroscience Research Volume: 185 Pages: 1-10
  • DOI: 10.1016/j.neures.2022.09.010
  • Peer Reviewed
• [Journal Article] Asymmetric Complexity in a Pupil Control Model With Laterally Imbalanced Neural Activity in the Locus Coeruleus: A Potential Biomarker for Attention-Deficit/Hyperactivity Disorder (2022)
  • Author(s): Kumano Hiraku、Nobukawa Sou、Shirama Aya、Takahashi Tetsuya、Takeda Toshinobu、Ohta Haruhisa、Kikuchi Mitsuru、Iwanami Akira、Kato Nobumasa、Toda Shigenobu
  • Journal Title: Neural Computation Volume: 34 Pages: 2388-2407
  • DOI: 10.1162/neco_a_01545
  • Peer Reviewed / Open Access
• [Presentation] ④左右瞳孔径挙動に基づくADHDの判別の検討と数理モデルによる神経活動推定 (2022)
  • Author(s): 信川 創、 熊野 開、白間 綾、髙橋 哲也、武田 俊信、太田 晴久、菊知 充、 岩波 明、加藤 進昌、戸田 重誠
  • Organizer: 日本成人ADHD学会
• [Presentation] 「DOHaD学」と精神神経疾患 (2022)
  • Author(s): 土屋賢治
  • Organizer: フォーラム2022：衛生薬学・環境トキシコロジー
  • Invited
• [Book] 発達障がい 病態から支援まで (2022)
  • Author(s): 谷池雅子，清水栄司，辻井正次，土屋賢治，松崎秀夫（編集）
  • Total Pages: 250
  • Publisher: 朝倉書店
• [Remarks]
  • URL: http://rccmd.net/