Interaction of genetic liability for attention deficit hyperactivity disorder (ADHD) and perinatal inflammation contributes to ADHD symptoms in children

Nagahide Takahashi; Tomoko Nishimura; Taeko Harada; Akemi Okumura; Toshiki Iwabuchi; Md Shafiur Rahman; Hitoshi Kuwabara; Shu Takagai; Noriyoshi Usui; Manabu Makinodan; Hideo Matsuzaki; Norio Ozaki; Hiroaki Itoh; Yoko Nomura; Jeffrey H. Newcorn; Kenji J. Tsuchiya

Brain, Behavior, & Immunity - Health (Jul 2023)

Interaction of genetic liability for attention deficit hyperactivity disorder (ADHD) and perinatal inflammation contributes to ADHD symptoms in children

Nagahide Takahashi,
Tomoko Nishimura,
Taeko Harada,
Akemi Okumura,
Toshiki Iwabuchi,
Md Shafiur Rahman,
Hitoshi Kuwabara,
Shu Takagai,
Noriyoshi Usui,
Manabu Makinodan,
Hideo Matsuzaki,
Norio Ozaki,
Hiroaki Itoh,
Yoko Nomura,
Jeffrey H. Newcorn,
Kenji J. Tsuchiya

Affiliations

Nagahide Takahashi: Department of Child and Adolescent Psychiatry, Nagoya University Graduate School of Medicine, Japan; Research Center for Child Mental Development, Hamamatsu University School of Medicine, Japan; United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Japan; Corresponding author. Department of Child and Adolescent Psychiatry, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8560, Japan.
Tomoko Nishimura: Research Center for Child Mental Development, Hamamatsu University School of Medicine, Japan; United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Japan
Taeko Harada: Research Center for Child Mental Development, Hamamatsu University School of Medicine, Japan; United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Japan
Akemi Okumura: Research Center for Child Mental Development, Hamamatsu University School of Medicine, Japan; United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Japan
Toshiki Iwabuchi: Research Center for Child Mental Development, Hamamatsu University School of Medicine, Japan; United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Japan
Md Shafiur Rahman: Research Center for Child Mental Development, Hamamatsu University School of Medicine, Japan; United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Japan
Hitoshi Kuwabara: Department of Psychiatry, Saitama University School of Medicine, Japan
Shu Takagai: United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Japan; Department of Child and Adolescent Psychiatry, Hamamatsu University School of Medicine, Japan
Noriyoshi Usui: Department of Neuroscience and Cell Biology, Graduate School of Medicine, Osaka University, Japan
Manabu Makinodan: Department of Psychiatry, Nara Medical University, Japan
Hideo Matsuzaki: United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Japan; Research Center for Child Mental Development, University of Fukui, Japan
Norio Ozaki: Pathophysiology of Mental Disorders, Nagoya University Graduate School of Medicine, Japan
Hiroaki Itoh: Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, Japan
Yoko Nomura: Queens College and Graduate Center, City University of New York, NY, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Jeffrey H. Newcorn: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Kenji J. Tsuchiya: Research Center for Child Mental Development, Hamamatsu University School of Medicine, Japan; United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Japan

Journal volume & issue: Vol. 30
p. 100630

Abstract

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Objective: Genetic and environmental factors contribute to the development of Attention Deficit/Hyperactivity Disorder (ADHD). Perinatal inflammation is one of the promising environmental risk factors for ADHD, but the relationship between the genetic risk for ADHD and perinatal inflammation requires further examination. Methods: A possible gene-environmental interaction between perinatal inflammation and ADHD polygenic risk score (ADHD-PRS) on ADHD symptoms was investigated in children aged 8–9 from the Hamamatsu Birth Cohort for Mothers and Children (N = 531). Perinatal inflammation was evaluated by the level of concentration of three cytokines assayed in umbilical cord blood. The genetic risk for ADHD was assessed by calculating ADHD-PRS for each individual using a previously collected genome-wide association study of ADHD. Results: Perinatal inflammation (β [SE], 0.263 [0.017]; P < 0.001), ADHD-PRS (β [SE], 0.116[0.042]; P = 0.006), and an interaction between the two (β [SE], 0.031[0.011]; P = 0.010) were associated with ADHD symptoms. The association between perinatal inflammation and ADHD symptoms measured by ADHD-PRS was evident only in the two higher genetic risk groups (β [SE], 0.623[0.122]; P < 0.001 for the medium-high risk group; β [SE], 0.664[0.152]; P < 0.001 for the high-risk group). Conclusion: Inflammation in the perinatal period both directly elevated ADHD symptoms and magnified the impact of genetic vulnerability on ADHD risk particularly among children aged 8–9 with genetically higher risk for ADHD.

Published in Brain, Behavior, & Immunity - Health

ISSN: 2666-3546 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/brain-behavior-and-immunity-health

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