Biomarkers for predominantly inattentive ADHD: potential involvement of Wnt/β-catenin/integrin signaling in a spontaneously hypertensive rat.

Abstract

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder marked by heterogeneous symptoms and comorbidities, complicating diagnosis and obscuring its neurobiological basis. OBJECTIVE: To investigate molecular mechanisms underlying ADHD, particularly the inattentive subtype, by examining Ctnnβ1 (catenin beta 1) and Itgβ1 (integrin beta 1), key components of the Wnt/β-catenin signaling pathway implicated in neurodevelopmental disorders. METHODS: Spontaneously hypertensive rats (SHR/NCrl), a validated ADHD model, were assessed for attentional performance through behavioral testing. Hippocampal and peripheral blood expression of Ctnnβ1 and Itgβ1 were quantified. A subset received atomoxetine to evaluate pharmacological effects on behavioral and molecular outcomes. RESULTS: SHR/NCrl rats displayed attentional impairments compared with controls. These deficits were accompanied by elevated hippocampal and peripheral expression of Ctnnβ1 and Itgβ1. Atomoxetine treatment normalized gene expression and improved attentional performance, demonstrating amelioration at both molecular and behavioral levels. CONCLUSION: Dysregulation of Wnt/β-catenin/integrin signaling may contribute to the ADHD pathophysiology. Concordant upregulation of Ctnnβ1 and Itgβ1 in brain and peripheral blood may support their potential as peripheral biomarkers of ADHD. Responsiveness of these genetic markers to atomoxetine treatment indicates potential value for treatment monitoring and supports targeting this pathway in future therapeutic strategies.