Borbye-Lorenzen Nis, Holmgaard Solveig, Ottosson Filip, Nudel Ron, Appadurai Vivek, Laursen Thomas Munk, Bækvad-Hansen Marie, Bybjerg-Grauholm Jonas, Nordentoft Merete, Børglum Anders D, Mortensen Preben Bo, Werge Thomas, Benros Michael E, Hougaard David Michael, Skogstrand Kristin
Danish Center for Neonatal Screening, Department of Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
Copenhagen Research Center for Biological and Precision Psychiatry, Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark; CORE - Copenhagen Research Center for Mental Health, Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark; iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.
Brain Behav Immun. 2025 Jan;123:99-107. doi: 10.1016/j.bbi.2024.09.009. Epub 2024 Sep 12.
Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder typically detected in childhood. Although ADHD has been demonstrated to have a strong genetic component, environmental risk factors, such as maternal infections during pregnancy, may also play a role. We therefore measured the immunological response to 5 abundant microorganisms (Toxoplasmosis Gondii, cytomegalovirus (CMV), Herpes Simplex Virus 1, Epstein Barr Virus and mycoplasma pneumoniae) in newborn heel prick samples of 1679 ADHD cases and 2948 matching controls as part of the iPSYCH Danish case-cohort study. We found an association between high anti-CMV (OR 1.30, 95 % CI [1.09,1.55], p = 0.015) and anti-mycoplasma (OR 1.30, 95 % CI [1.07,1.59], p = 0.037) signal and those newborns later being diagnosed with ADHD. The risk estimate remained increased when controlling for ADHD polygenic risk score as well as penicillin prescriptions. We saw a dose-response association with the amount of positive anti-microorganism titers increasing the risk of being diagnosed with ADHD later in life (p = 0.01 for the trend), suggesting that the more activated the immune system is prior to or at birth, the higher the risk is for a later diagnosis with ADHD. If the associations are causal, they emphasize the importance of a healthy life style during pregnancy to reduce the risk of infections when pregnant and the associated risks for the child.
注意力缺陷多动障碍（ADHD）是一种通常在儿童期被检测出的神经发育障碍。尽管已证明ADHD有很强的遗传因素，但环境风险因素，如孕期母亲感染，也可能起作用。因此，作为iPSYCH丹麦病例队列研究的一部分，我们在1679例ADHD病例和2948例匹配对照的新生儿足跟血样本中，测量了对5种常见微生物（弓形虫、巨细胞病毒（CMV）、单纯疱疹病毒1型、爱泼斯坦-巴尔病毒和肺炎支原体）的免疫反应。我们发现，抗CMV高信号（比值比1.30，95%置信区间[1.09，1.55]，p = 0.015）和抗支原体高信号（比值比1.30，95%置信区间[1.07，1.59]，p = 0.037）与那些后来被诊断为ADHD的新生儿之间存在关联。在控制ADHD多基因风险评分以及青霉素处方后，风险估计值仍然升高。我们观察到抗微生物阳性滴度数量与日后被诊断为ADHD的风险之间存在剂量反应关联（趋势p = 0.01），这表明在出生前或出生时免疫系统激活程度越高，日后被诊断为ADHD的风险就越高。如果这些关联是因果关系，它们强调了孕期保持健康生活方式以降低孕期感染风险及对孩子相关风险的重要性。
