Associations Between Eczema and Attention Deficit Hyperactivity Disorder Symptoms in Children

Evelyn Xiu Ling Loo, Delicia Shu Qin Ooi, Minyee Ong, Le Duc Huy Ta, Hui Xing Lau, Michelle Jia Yu Tay, Qai Ven Yap, Yiong Huak Chan, Elizabeth Huiwen Tham, Anne Eng Neo Goh, Hugo Van Bever, Oon Hoe Teoh, Johan Gunnar Eriksson, Yap Seng Chong, Peter Gluckman, Fabian Kok Peng Yap, Neerja Karnani, Jia Xu, Karen Mei Ling Tan, Kok Hian Tan, Bee Wah Lee, Michael Kramer, Lynette Pei-Chi Shek, Michael J Meaney, Birit F P Broekman, Evelyn Xiu Ling Loo, Delicia Shu Qin Ooi, Minyee Ong, Le Duc Huy Ta, Hui Xing Lau, Michelle Jia Yu Tay, Qai Ven Yap, Yiong Huak Chan, Elizabeth Huiwen Tham, Anne Eng Neo Goh, Hugo Van Bever, Oon Hoe Teoh, Johan Gunnar Eriksson, Yap Seng Chong, Peter Gluckman, Fabian Kok Peng Yap, Neerja Karnani, Jia Xu, Karen Mei Ling Tan, Kok Hian Tan, Bee Wah Lee, Michael Kramer, Lynette Pei-Chi Shek, Michael J Meaney, Birit F P Broekman

Abstract

Background: Epidemiological studies suggest a link between eczema and attention deficit hyperactivity disorder (ADHD), but underlying mechanisms have not been examined.

Objective: We aim to investigate the association between eczema and subsequent ADHD symptoms in the Growing Up in Singapore Towards healthy Outcomes cohort and explore the role of pro-inflammatory cytokines and gut microbiome.

Methods: The modified International Study of Asthma and Allergies in Childhood questionnaire and Computerized Diagnostic Interview Schedule for Children Version IV were administered to assess reported eczema within the first 18 months and presence of ADHD symptoms at 54 months, respectively. Skin prick testing at 18 months, cytokines in maternal blood during pregnancy and cord blood and the mediating role of the gut microbiome at 24 months were assessed.

Results: After adjusting for confounders, eczema with or without a positive skin prick test was associated with doubling the risk of ADHD symptoms. No differences in maternal and cord blood cytokines were observed in children with and without eczema, or children with and without ADHD. Gut microbiome dysbiosis was observed in children with eczema and children with ADHD. Children with eczema also had lower gut bacterial Shannon diversity. However, the relationship between eczema and ADHD was not mediated by gut microbiome.

Conclusion: Early life eczema diagnosis is associated with a higher risk of subsequent ADHD symptoms in children. We found no evidence for underlying inflammatory mechanism or mediation by gut microbiome dysbiosis. Further research should evaluate other mechanisms underlying the link between eczema and ADHD.

Clinical trial registration: [https://ichgcp.net/clinical-trials-registry/NCT01174875], identifier [NCT01174875].

Keywords: atopy; attention deficit hyperactivity disorder; cytokines; eczema; gut microbiome dysbiosis.

Conflict of interest statement

YSC and NK are part of an academic consortium that has received research funding from Abbot Nutrition, Nestle and Danone. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Loo, Ooi, Ong, Ta, Lau, Tay, Yap, Chan, Tham, Goh, Van Bever, Teoh, Eriksson, Chong, Gluckman, Yap, Karnani, Xu, Tan, Tan, Lee, Kramer, Shek, Meaney and Broekman.

Figures

FIGURE 1
FIGURE 1
Comparisons of bacterial candidates in gut microbiome at 24 months between children with and without (A) eczema by 18 months (n = 72 vs 250), (B) ADHD symptoms at 54 months (n = 65 vs 196). Data are presented as median. Only significant bacteria (adjusted p < 0.05) with reference to controls were shown.

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