Early life injuries and the development of attention deficit/hyperactivity disorder

OBJECTIVES: 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 1995-2010 (n=786,543) were followed from age five until a median age of 14 (IQR: 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 five. In a subsample born 1995 to 2005 with genetic data available (n=16,580), we estimated incidence rate ratios (IRR) for the association between PRS-ADHD and number of injuries before age five and the genetic correlation between ADHD and any injury before age five. 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, stronger in 1(st)- than 2(nd)-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 behaviour 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.