TY - JOUR
T1 - High level of immunoglobulin G targeting mycoplasma or cytomegalovirus in the newborn increases risk of ADHD
AU - Borbye-Lorenzen, Nis
AU - Holmgaard, Solveig
AU - Ottosson, Filip
AU - Nudel, Ron
AU - Appadurai, Vivek
AU - Laursen, Thomas Munk
AU - Bækvad-Hansen, Marie
AU - Bybjerg-Grauholm, Jonas
AU - Nordentoft, Merete
AU - Børglum, Anders D
AU - Mortensen, Preben Bo
AU - Werge, Thomas
AU - Benros, Michael E
AU - Hougaard, David Michael
AU - Skogstrand, Kristin
N1 - Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2025/1
Y1 - 2025/1
N2 - 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.
AB - 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.
KW - Cytomegalovirus
KW - Dried blood spots
KW - IgG
KW - Infection
KW - Maternal immune activation
KW - Multiplex immuno assay
KW - Mycoplasma
KW - Serology
KW - iPSYCH
UR - http://www.scopus.com/inward/record.url?scp=85203495130&partnerID=8YFLogxK
U2 - 10.1016/j.bbi.2024.09.009
DO - 10.1016/j.bbi.2024.09.009
M3 - Journal article
C2 - 39260764
SN - 0889-1591
VL - 123
SP - 99
EP - 107
JO - Brain, Behavior, and Immunity
JF - Brain, Behavior, and Immunity
ER -