Imaging genetics of neural network in ADHD using resting state fMRI

• Project/Area Number: 18K13106
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 09030:Childhood and nursery/pre-school education-related
• Research Institution: University of Fukui
• Principal Investigator: Mizuno Yoshifumi 福井大学, 子どものこころの発達研究センター, 特別研究員 (50756814)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 注意欠如多動症（ADHD） / 自閉スペクトラム症（ASD) / 構造的MRI / 中心後回 / 自閉スペクトラム症（ASD） / 注意欠如・多動症（ADHD） / COMT遺伝子多型 / 脳構造画像 / 自閉スペクトラム症(ASD) / 安静時機能的MRI / 構造画像 / 機械学習 / COMT / ADHD / imaging genetics

Outline of Final Research Achievements

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) share high rates of comorbidity. However, no structural studies have focused on patients with comorbid ASD and ADHD. We thus aimed to clarify the structural features and developmental changes in patients with comorbid ASD and ADHD in a relatively large sample from two sites. Ninety-two patients and 141 typically developing (TD) controls were assessed for volumetric characteristics using structural MRI. Patients with ASD and ADHD exhibited significantly lower left postcentral gyrus volumes than TD controls. We observed significantly lower postcentral gyrus volumes exclusively in children and preadolescents, and not in adolescents. Our findings suggest that abnormal somatosensory, attributed to delayed maturation of the left postcentral gyrus, leads to the core symptoms experienced by patients with comorbid ASD and ADHD.

Academic Significance and Societal Importance of the Research Achievements

福井大学と大阪大学によって比較的多数のサンプルを集積して解析を行った結果、これまで明らかにされていなかった自閉スペクトラム症（ASD）と注意欠如多動症（ADHD）の併存例における脳構造の特徴と発達による変化が明らかとなった。この成果はASD・ADHDのの病態解明に貢献し、ASD・ADHDを客観的に評価するためのバイオマーカーの開発につながる可能性がある。

Research Products

• [Int'l Joint Research] スタンフォード大学(米国)
• [Journal Article] 「神経発達症」に関する研究の最前線 -連合小児発達学研究科の取り組み (2020)
  • Author(s): 水野賀史、友田明美
  • Journal Title: 小児の精神と神経 Volume: 60 Pages: 218-222
  • NAID: 130007920793
• [Journal Article] Thalamic Volume Is Related to Increased Anterior Thalamic Radiations in Children with Reactive Attachment Disorder (2020)
  • Author(s): Jung Minyoung、Takiguchi Shinichiro、Hamamura Shoko、Mizuno Yoshifumi、Kosaka Hirotaka、Tomoda Akemi
  • Journal Title: Cerebral Cortex Volume: - Issue: 7 Pages: 4238-4245
  • DOI: 10.1093/cercor/bhaa051
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Structural brain abnormalities in children and adolescents with comorbid autism spectrum disorder and attention-deficit/hyperactivity disorder (2019)
  • Author(s): Mizuno Y, Kagitani-Shimono K, Jung M, Makita K, Takiguchi S, Fujisawa TX, Tachibana M, Nakanishi M, Mohri I, Taniike M, Tomoda A.
  • Journal Title: Transl Psychiatry. Volume: 9 Issue: 1 Pages: 332-332
  • DOI: 10.1038/s41398-019-0679-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] ADHDの薬物療法 (2019)
  • Author(s): 水野 賀史、友田 明美
  • Journal Title: モダンフィジシャン Volume: 39 Pages: 1139-1141
• [Journal Article] The effects of COMT polymorphism on cortical thickness and surface area abnormalities in children with ADHD (2018)
  • Author(s): Jung M, Mizuno Y (co-first author), Fujisawa TX, Takiguchi S, Kong J, Kosaka H, Tomoda A
  • Journal Title: Cerebral Cortex Volume: - Issue: 9 Pages: 3902-3911
  • DOI: 10.1093/cercor/bhy269
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] AD/HDの脳機能 (2018)
  • Author(s): 水野賀史, 島田浩二, 滝口慎一郎, 友田明美
  • Journal Title: 日本臨牀 Volume: 76 Pages: 544-548
  • NAID: 40021529342
• [Journal Article] ADHDにおける遺伝子の脳画像の関連解析 (2018)
  • Author(s): 水野賀史, 島田浩二, 滝口慎一郎, 友田明美
  • Journal Title: BIO INDUSTRY Volume: 35 Pages: 10-17
• [Presentation] Effects of methylphenidate on aberrant brain network dynamics in children with attention-deficit/hyperactivity disorder : a randomized controlled clinical trial (2021)
  • Author(s): Mizuno Y, Cai W, Supekar, K, Makita K, Takiguchi S, Tomoda A, Menon V
  • Organizer: 2021 Society of Biological Psychiatry Annual Meeing
  • Int'l Joint Research
• [Presentation] Structural brain abnormalities in children and adolescents with comorbid autism spectrum disorder and attention-deficit/hyperactivity disorder (2020)
  • Author(s): Mizuno Y, Jung M, Makita K, Takiguchi S, Fujisawa TX, Tomoda A
  • Organizer: American Academy of Child and Adolescent Psychiatry’s 67th Annual Meeting
  • Int'l Joint Research
• [Presentation] Structural classification feature in children with ADHD using machine learning approach (2019)
  • Author(s): Mizuno Y, Jung M, Fujisawa TX, Takiguchi S, Kosaka H, Tomoda A
  • Organizer: 第61回日本小児神経学会学術集会
• [Presentation] MRIを用いた神経発達症に対する脳画像研究 (2019)
  • Author(s): 水野 賀史
  • Organizer: 第122回日本小児精神神経学会
• [Presentation] ADHD児における構造的ネットワークの変化 (2018)
  • Author(s): 水野賀史, 丁ミンヨン, 滝口慎一郎, 友田明美
  • Organizer: 第60回日本小児神経学会学術集会
• [Presentation] COMT genotype affect cortical thickness and surface area abnormalities in boys with ADHD -Machine learning and imaging genetics approach to ADHD- (2018)
  • Author(s): Jung M, Mizuno Y, Fujisawa TX, Takiguchi S, Kosaka H, Tomoda A
  • Organizer: 第2回ヒト脳イメージング研究会
• [Presentation] The Effects of Catechol-O-Methyltransferase (COMT) Polymorphism on Cortical Thickness and Surface Area Abnormalities in Children With ADHD (2018)
  • Author(s): Mizuno Y, Jung M, Fujisawa TX, Takiguchi S, Kosaka H, Tomoda A
  • Organizer: AACAP's 65th Annual Meeting
  • Int'l Joint Research
• [Presentation] ADHD児における大脳皮質厚と表面積に対するCOMT遺伝子多型の影響 (2018)
  • Author(s): 水野賀史, 滝口慎一郎, 友田明美
  • Organizer: 日本小児精神神経学会第120回記念大会