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

doi:10.1016/j.bbih.2023.100630

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

Brain Behav Immun Health. 2023 May 18:30:100630. doi: 10.1016/j.bbih.2023.100630. eCollection 2023 Jul.

Authors

Nagahide Takahashi^{1

2

3}, Tomoko Nishimura^{2

3}, Taeko Harada^{2

3}, Akemi Okumura^{2

3}, Toshiki Iwabuchi^{2

3}, Md Shafiur Rahman^{2

3}, Hitoshi Kuwabara⁴, Shu Takagai^{3

5}, Noriyoshi Usui⁶, Manabu Makinodan⁷, Hideo Matsuzaki^{3

8}, Norio Ozaki⁹, Hiroaki Itoh¹⁰, Yoko Nomura^{11

12}, Jeffrey H Newcorn¹², Kenji J Tsuchiya^{2

3}

Affiliations

¹ Department of Child and Adolescent Psychiatry, Nagoya University Graduate School of Medicine, Japan.
² Research Center for Child Mental Development, Hamamatsu University School of Medicine, Japan.
³ United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Japan.
⁴ Department of Psychiatry, Saitama University School of Medicine, Japan.
⁵ Department of Child and Adolescent Psychiatry, Hamamatsu University School of Medicine, Japan.
⁶ Department of Neuroscience and Cell Biology, Graduate School of Medicine, Osaka University, Japan.
⁷ Department of Psychiatry, Nara Medical University, Japan.
⁸ Research Center for Child Mental Development, University of Fukui, Japan.
⁹ Pathophysiology of Mental Disorders, Nagoya University Graduate School of Medicine, Japan.
¹⁰ Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, Japan.
¹¹ Queens College and Graduate Center, City University of New York, NY, USA.
¹² Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Abstract

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.

Keywords: Attention deficit hyperactivity disorder; Cord blood; Cytokine; Inflammation; Polygenic risk score.