Regulators of Wnt Signaling Dkk‐1 and Notum Are Elevated in Pediatric ADHD

Wnt signaling has increasingly drawn attention in discussions of ADHD, yet the peripheral status of its upstream regulators remains largely uncharted. In this study, we examined circulating levels of four key modulators of this pathway-Dkk-1, PORCN, Notum, and Tiki-1-in a sample of children and adolescents with an ADHD diagnosis. A total of 158 children and adolescents, comprising 82 with ADHD and 76 healthy controls aged 8-18 years, were enrolled. ADHD diagnoses were established according to DSM-5 criteria utilizing the K-SADS-PL questionnaire. The severity of ADHD symptoms was assessed using scores from the Turgay DSM-IV-Based Screening and Evaluation Scale for Attention Deficit and Disruptive Behavior Disorders-Parent Form (T-DSM-IV-S). Serum levels of Dkk-1, PORCN, Notum, and Tiki-1 were quantified using ELISA kits. Children with ADHD demonstrated markedly increased serum concentrations of Dkk-1 and Notum relative to controls (p < 0.01). Elevated PORCN levels were also observed; however, this finding should be interpreted with caution (p < 0.01). Tiki-1 levels showed no significant difference between the groups. No substantial relationships were detected between serum concentrations of the studied analytes and the severity of ADHD symptoms. The significance of these findings was maintained after adjustment for age and sex. This study extends the literature by examining peripheral concentrations of Dkk-1, PORCN, Notum, and Tiki-1 in ADHD. The elevated levels of Dkk-1 and Notum may reflect alterations in Wnt-related signaling pathways, while the interpretation of PORCN findings remains limited. Taken together, these findings indicate peripheral molecular differences associated with ADHD and provide a basis for future research investigating Wnt-related signaling pathways in ADHD. However, these results should be interpreted as exploratory findings requiring further validation using complementary analytical approaches.