Serum β-catenin, GSK-3β, and IL-6 levels in medication-naive children with ADHD: a preliminary case-control study

Abstract: Attention-deficit/hyperactivity disorder (ADHD) has been associated with alterations in neurodevelopmental signaling pathways and inflammatory processes. This study compared serum β-catenin, glycogen synthase kinase-3 beta (GSK-3β), and interleukin-6 (IL-6) levels between medication-naive children with ADHD and healthy controls and examined associations among these biomarkers. Forty-five medication-naive children aged 7–13 years with ADHD and 45 healthy controls were included. ADHD diagnoses followed DSM-5 criteria. Serum β-catenin, GSK-3β, and IL-6 levels were measured by enzyme-linked immunosorbent assay. Group differences were assessed using covariate-adjusted analyses (age, sex, BMI percentile) with Bonferroni correction. Correlations were examined in the ADHD group, control group, and total cohort. Serum GSK-3β and IL-6 levels were higher in the ADHD group than in controls; both differences remained significant after covariate adjustment and Bonferroni correction (p<.001). β-catenin levels were lower in the ADHD group in the unadjusted analysis but were not significant after correction. Within the ADHD group, β-catenin, GSK-3β, and IL-6 showed correlations that remained significant after correction. No significant correlations were observed in the control group; in the total cohort, only the GSK-3β–IL-6 correlation remained significant after correction. No biomarker was associated with symptom severity. Medication-naive children with ADHD showed higher serum GSK-3β and IL-6 levels than controls, warranting further investigation of peripheral signaling and inflammatory differences, though the absence of technical replicates warrants caution. The β-catenin finding was not confirmed after correction. Because phosphorylated forms were not assessed, the findings do not establish altered Wnt pathway activity or GSK-3β function. Longitudinal and functional studies are needed to clarify these findings.