Serum TLR4, NF-κB, and NLRP3 Levels in Children with Attention-Deficit/Hyperactivity Disorder: A Case-Control Study

Background: Increasing evidence suggests that inflammatory processes may be involved in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). However, clinical data regarding TLR4, NF-κB and NLRP3 in children with ADHD remain limited. This study aimed to compare serum TLR4, NF-κB, and NLRP3 levels between children with ADHD and healthy controls and to examine the associations between these inflammatory markers and ADHD symptom severity. Methods: A total of 42 children with ADHD and 40 age- and sex-matched healthy controls were enrolled. ADHD symptoms were assessed using the Conners' Parent Rating Scale-Revised Short Form (CPRS-RS) and the Conners' Teacher Rating Scale-Revised Short Form (CTRS-RS). Serum TLR4, NF-κB, and NLRP3 levels were measured using enzyme-linked immunosorbent assay (ELISA). Between-group comparisons were performed after adjustment for age, sex, and body mass index (BMI), and correlations between inflammatory markers and symptom severity were evaluated. Results: Serum NF-κB and NLRP3 levels were significantly higher in children with ADHD than in healthy controls, whereas serum TLR4 levels did not differ between groups. Serum NF-κB levels showed a moderate positive correlation with teacher-rated hyperactivity scores, while no significant associations were observed between TLR4 or NLRP3 levels and ADHD symptom severity in the ADHD group. Conclusions: Our findings provide preliminary clinical evidence of altered NF-κB and NLRP3 levels in children with ADHD. The absence of a significant difference in serum TLR4 levels, despite increased NF-κB and NLRP3 levels, suggests that these inflammatory components may be differentially altered in ADHD. Further longitudinal and mechanistic studies are needed to clarify the relevance of these inflammatory alterations to ADHD pathophysiology.