Identification of common endophenotypes and aetiological pathways leading to the emergence of autism spectrum disorder and attention-deficit hyperactive disorder

• Project/Area Number: 16H05374
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Tsuchiya Kenji 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): 高貝 就 浜松医科大学, 医学部, 特任教授 (10447807)
• Research Collaborator: SATA Fumihiro ; ITOH Hiroaki ; TAKEI Noriyoshi ; WAKUSAWA Keisuke
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2018: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2017: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
• Keywords: 自閉スペクトラム症 / 注意欠如・多動症 / 出生コホート / 神経発達 / 軌跡 / 自閉スペクトラム症（ / 疫学 / コホート研究 / 中間表現型 / 発達障がい / 環境化学物質

Outline of Final Research Achievements

[Overlap between ASD and ADHD phenotypes] The ADHD phenotype was not specifically associated with social domain nor with repetitive behavior domain of the ASD phenotype, but was significantly associated with those having higher scores in both social and repetitive behavior domains. This suggests individuals having both ASD and ADHD phenotypes are likely to have both social and repetitive behavior problems.
[Overlap between ASD and ADHD endophenotypes and neurodevelopmental trajectories through the first four years of life] In our study subjects, ASD group and ASD+ADHD group both showed delay in neurodevelopment, and ADHD group also showed a similar trend between 0 to 2 years of life. ADHD group, however, showed departure from other two groups after 2 years old.

Academic Significance and Societal Importance of the Research Achievements

1．ASD児・者，およびASDとADHDが併存する児・者の神経発達の軌跡，すなわち2歳前の神経発達の遅延がみられることが共通していた。現在の乳幼児健診システムにおいて，両者を早期に発見することが可能であることが明らかとなった。
2．一方，ASD傾向をもたないADHD児・者は，わずかに神経発達の遅延を示しながらも，その遅延はドメインごとに偏りがあること（粗大運動の遅延は目立たないが微細運動の遅延が目立つこと），その偏りが2歳以降に明らかになっていくことが示された。
3．乳幼児健診のあり方に関する新たな指針が得られた。

Research Products

• [Int'l Joint Research] ニューヨーク市立大学(米国)
• [Int'l Joint Research] ニューヨーク市立大学クイーンズ校(米国)
• [Int'l Joint Research] オールボー大学(デンマーク)
• [Journal Article] Association of late-onset postpartum depression of mothers with expressive language development during infancy and early childhood: the HBC study (2019)
  • Author(s): Aoyagi SS, Takei N, Nishimura T, Nomura Y, Tsuchiya KJ.
  • Journal Title: PeerJ Volume: 7 Pages: e6566-e6566
  • DOI: 10.7717/peerj.6566
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Sensory processing in children with autism spectrum disorder and the mental health of primary caregivers (2019)
  • Author(s): Suzuki Kanae、Takagai Shu、Tsujii Masatsugu、Ito Hiroyuki、Nishimura Tomoko、Tsuchiya Kenji J.
  • Journal Title: Brain and Development Volume: 41 Issue: 4 Pages: 341-351
  • DOI: 10.1016/j.braindev.2018.11.005
  • Peer Reviewed
• [Journal Article] Influence of in utero exposure to maternal depression and natural disaster-related stress on infant temperament at 6 months: The children of Superstorm Sandy (2019)
  • Author(s): Nomura Y, Davey K, Pehme PM, Finik J, Glover V, Zhang W, Huang Y, Buthmann J, Dana K, Yoshida S, Tsuchiya KJ, Li XB, Ham J
  • Journal Title: Infantile Mental Health Journal Volume: - Issue: 2 Pages: 204-216
  • DOI: 10.1002/imhj.21766
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Timing of Prenatal Exposure to Trauma and Altered Placental Expressions of HPA- Axis Genes and Genes Driving Neurodevelopment (2018)
  • Author(s): Wei Zhang, Qian Li, Maya Deyssenroth, Luca Lambertini, Jackie Finik, Jacob Ham, Yongling Huang, Kenji J Tsuchiya, Patricia Pehme, Jessica Buthmann, Sachiko Yoshida, Jia Chen, Yoko Nomura
  • Journal Title: J. Neuroendocrinology Volume: 30（４） Issue: 4
  • DOI: 10.1111/jne.12581
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Placental pathology predicts infantile physical development during first 18 months in Japanese population: Hamamatsu birth cohort for mothers and children (HBC Study) (2018)
  • Author(s): Yaguchi Chizuko、Itoh Hiroaki、Tsuchiya Kenji J.、Furuta-Isomura Naomi、Horikoshi Yoshimasa、Matsumoto Masako、Jeenat Ferdous U.、Keiko Muramatsu-Kato、Kohmura-Kobatashi Yukiko、Tamura Naoaki、Sugihara Kazuhiro、Kanayama Naohiro
  • Journal Title: PLOS ONE Volume: 13 Issue: 4 Pages: e0194988-e0194988
  • DOI: 10.1371/journal.pone.0194988
  • Peer Reviewed / Open Access
• [Journal Article] A cross-continental analysis of weight gain, psychiatric diagnoses and medication use during inpatient psychiatric treatment. The international study on physical illness in mentally ill (2018)
  • Author(s): Engelke C, Lange-Asschenfeldt C, Peter S, Kahl KG, Frasch K, Larsen JI, Bickel GG, Bork B, Jacobsen BA, Wallenstein-Jensen SO, Lauber C, Mogensen B, Nielsen JA, Rossler W, Tsuchiya KJ, Toftegaard KL, Andersen UA, Uwakwe R, Munk-Jorgensen P, Cordes J
  • Journal Title: European Psychiatry Volume: 48 Issue: 1 Pages: 65-70
  • DOI: 10.1016/j.eurpsy.2017.11.004
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Birth Cohort Consortium of Asia: Current and Future Perspectives (2017)
  • Author(s): Kishi R, Zhang JJ, Ha EH, Chen PC, Tian Y, Xia Y, Tsuchiya KJ, Nakai K, Kim S, Hong SJ, Hong YC, Lee JR, Jan Mohamed HJB, Parajuli RP, Adair LS, Chong YS, Guo YL, Wang SL, Nishijo M, Kido T, Tai PT, Nandasena S
  • Journal Title: Epidemiology Volume: 28 Suppl 1 Pages: S19-S34
  • DOI: 10.1097/ede.0000000000000698
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Maternal postpartum depressive symptoms predict delay in non-verbal communication in 14-month-old infants. (2016)
  • Author(s): Kawai E, Takagai S, Takei N, Itoh H, Kanayama N, Tsuchiya JK, for HBC Study Team.
  • Journal Title: Infant Behav Dev Volume: 46 Pages: 33-35
  • DOI: 10.1016/j.infbeh.2016.11.006
  • Peer Reviewed
• [Journal Article] Cohort profile: Hamamatsu Birth Cohort for Mothers and Children (HBC Study) (2016)
  • Author(s): Takagai S, Tsuchiya KJ, Itoh H, Kanayama N, Mori N, Takei N, on behalf of HBC Study Team
  • Journal Title: International Journal of Epidemiology Volume: 45 Issue: 2 Pages: 333-342
  • DOI: 10.1093/ije/dyv290
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Season of birth predicts emotional and behavioral regulation in 18-Month-Old Infants: Hamamatsu Birth Cohort for Mothers and Children (HBC Study) (2016)
  • Author(s): Asano R, Tsuchiya KJ, Harada T, Kugizaki Y, Nakahara R, Nakayasu C, Okumura A, Suzuki Y, Takagai S, Mori N, Takei N; for Hamamatsu Birth Cohort (HBC) Study Team
  • Journal Title: Frontiers in Public Health Volume: 4 Pages: 152-152
  • DOI: 10.3389/fpubh.2016.00152
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Language development during childhood is affected by maternal postpartum depression, not by unwanted pregnancy: HBC Study (2019)
  • Author(s): Tsuchiya KJ, Aoyagi SS, Nomura Y, Yoshida S, Nishimura T, Choi D, Harada T, Iwabuchi T, Nakahara R, Okumura A
  • Organizer: The 9th FAOPS Congress
  • Int'l Joint Research
• [Presentation] 浜松母と子の出生コホート研究 パーフルオロ化合物と児の発達障がいのリスク (2017)
  • Author(s): 土屋賢治
  • Organizer: 第6回日本DOHaD学会学術集会
  • Invited
• [Presentation] 出生～発達の偏り～ASD 浜松母と子の出生コホート研究から (2017)
  • Author(s): 土屋賢治
  • Organizer: 第58回日本児童青年精神医学会総会
  • Invited
• [Presentation] Neurodevelopmental trajectories of children during the first two years of life: how deviant is the trajectory if the child is later diagnosed as having autism spectrum disorder? (2016)
  • Author(s): Tsuchiya KJ
  • Organizer: The 18th International Organization of Psychophysiology World Congress
  • Place of Presentation: Havana, Cuba
  • Year and Date: 2016-09-01
  • Int'l Joint Research
• [Presentation] Paternal age at birth and neurodevelopment in the offspring (2016)
  • Author(s): Tsuchiya KJ, Nishimura T, Takagai S
  • Organizer: International Society for Environmental Epidemiology and International Society for Exposure Science Asia Chapter
  • Place of Presentation: Sapporo, Japan
  • Year and Date: 2016-06-27
  • Int'l Joint Research / Invited
• [Remarks] 浜松医科大学子どものこころの発達研究センター
  • URL: http://www.rccmd.org/
• [Remarks] 子どものこころの発達研究センター 私たちの研究を紹介します
  • URL: http://rccmd.org/modules/center/index.php?content_id=2
• [Patent(Industrial Property Rights)] 1.不注意の測定装置、システム、及び方法 (2016)
  • Inventor(s): 森則夫、鈴木勝昭、土屋賢治、新村千江
  • Industrial Property Rights Holder: 森則夫、鈴木勝昭、土屋賢治、新村千江
  • Industrial Property Rights Type: 特許
  • Filing Date: 2016
  • Acquisition Date: 2017