The role of inflammation in the prospective associations between early childhood sleep problems and ADHD at 10 years: findings from a UK birth cohort study

Background: Several underlying mechanisms potentially account for the link between sleep and attention deficit and hyperactivity disorder (ADHD), including inflammation. However, studies so far have been cross sectional. We investigate (a) the association between early childhood sleep and probable ADHD diagnosis in childhood and (b) whether childhood circulating inflammatory markers mediate these prospective associations. Methods: Data from the Avon Longitudinal Study of Parents and Children were available for 7,658 10-year-old children. Parent-reported sleep duration, night awakening frequency and regular sleep routines were collected at 3.5 years. The Development and Wellbeing Assessment was administered to capture children with clinically relevant ADHD symptoms, or probable ADHD diagnosis. Blood samples were collected at 9 years, from which two inflammatory markers were obtained [interleukin-6 (IL-6) and C-reactive protein (CRP)]. Logistic regression analyses were applied to investigate the associations between sleep variables at 3.5 years and probable ADHD diagnosis at 10 years. Further, path analysis was applied to examine the potential mediating role of inflammation at 9 years (as measured by CRP and IL�6) in the associations between early sleep and ADHD at 10 years. Results: Less regular sleep routines (OR = 0.51, 95% CI = 0.28–0.93, p = .029), shorter nighttime sleep (OR = 0.70, 95% CI = 0.56–0.89, p = .004) and higher night awakening frequency (OR = 1.27, 95% CI = 1.06–1.52, p = .009) at 3.5 years were associated with higher odds of ADHD at 10 years. Further, IL-6 at 9 years, but not CRP, mediated the association between irregular sleep routines and ADHD (bias-corrected estimate, �0.002; p = .005) and between night awakening and ADHD (bias-corrected estimate, 0.002; p = .003). Conclusions: Several sleep problems in early childhood constitute a risk factor for probable ADHD diagnosis at 10 years. Further, these associations are partially mediated by IL-6 at 9 years. These results open a new research vista to the pathophysiology of ADHD and highlight sleep and inflammation as potential preventative targets for ADHD. Keywords: Sleep; ADHD; inflammatory markers; ALSPAC; longitudinal.