Association of Inflammatory Biomarkers With ADHD and Moderating Effect of Leisure-Time Physical Activity in Adolescents: A Cross-Sectional Study Based on NHANES

Introduction: Research findings on specific inflammatory markers (e.g., CRP) in ADHD show considerable heterogeneity. Meanwhile, the potential moderating role of leisure-time physical activity (LTPA) in this relationship is underexplored. Methods: Based on data from the National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2004, 4,817 adolescents aged 12 to 19 were included. This study used logistic regression analysis and restricted cubic splines (RCS) to explore the association between inflammatory biomarkers and ADHD. Interactive analyses were performed to assess the moderating effect of LTPA on this relationship. Furthermore, subgroup analyses were conducted to validate the robustness of the observed effects. Results: After adjusting for all confounding factors, each 1 mg/L increment in C-reactive protein (CRP) was associated with a 9% higher ADHD risk ( OR = 1.09, 95% CI [1.01, 1.18]). The chronic low-grade inflammation (CLGI) group exhibited a 57% higher risk of ADHD ( OR = 1.57, 95% CI [1.14, 2.15]) compared to the non-GLGI group. The non-linear analysis further revealed that the risk of ADHD reached its peak when CRP was 2.75 mg/L ( OR = 1.89, 95% CI [1.39, 2.57]). Compared with the group engaging in less than 60 min of LTPA daily, the association between ADHD and CRP was moderated in the “LTPA ≥60 min/day” group ( p for interaction = .04). Conclusions: Elevated CRP levels are positively associated with ADHD. More than 60 min/day LTPA may moderate the association between CRP and the risk of ADHD.