Early-Life Injuries and the Development of Attention-Deficit/Hyperactivity Disorder

Theresa Wimberley*, Isabell Brikell, Emil M. Pedersen, Esben Agerbo, Bjarni J. Vilhjálmsson, Clara Albiñana, Florian Privé, Anita Thapar, Kate Langley, Lucy Riglin, Marianne Simonsen, Helena S. Nielsen, Anders D. Børglum, Merete Nordentoft, Preben B. Mortensen, Søren Dalsgaard

*Corresponding author for this work

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Abstract

Objective: To estimate phenotypic and familial association between early-life injuries and attention-deficit/hyperactivity disorder (ADHD) and the genetic contribution to the association using polygenic risk score for ADHD (PRS-ADHD) and genetic correlation analyses. Methods: Children born in Denmark between 1995–2010 (n = 786,543) were followed from age 5 years until a median age of 14 years (interquartile range: 10–18 years). Using ICD-10 diagnoses, we estimated hazard ratios (HRs) and absolute risks of ADHD by number of hospital/emergency ward–treated injuries by age 5. In a subset of ADHD cases and controls born 1995 to 2005 who had genetic data available (n = 16,580), we estimated incidence rate ratios (IRRs) for the association between PRS-ADHD and number of injuries before age 5 and the genetic correlation between ADHD and any injury before age 5. Results: Injuries were associated with ADHD (HR = 1.61; 95% CI, 1.55–1.66) in males (HR = 1.59; 1.53–1.65) and females (HR = 1.65; 1.54–1.77), with a dose-response relationship with number of injuries. The absolute ADHD risk by age 15 was 8.4% (3+ injuries) vs 3.1% (no injuries). ADHD was also associated with injuries in relatives, with a stronger association in first- than second-degree relatives. PRS-ADHD was marginally associated with the number of injuries in the general population (IRR = 1.06; 1.00–1.14), with a genetic correlation of 0.53 (0.21–0.85). Conclusions: Early-life injuries in individuals and their relatives were associated with a diagnosis of ADHD. However, even in children with the most injuries, more than 90% were not diagnosed with ADHD by age 15. Despite a low positive predictive value and that the impact of unmeasured factors such as parental behavior remains unclear, results indicate that the association is partly explained by genetics, suggesting that early-life injuries may represent or herald early behavioral manifestations of ADHD.

Original languageEnglish
Article number21m14033
JournalJournal of Clinical Psychiatry
Volume83
Issue number1
Number of pages19
ISSN0160-6689
DOIs
Publication statusPublished - 2022

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