Astrocytic extracellular matrix proteins in ADHD: The role of Thrombospondin-1, Sparc, and Sparcl-1.

Astrocyte-derived extracellular matrix (ECM) proteins are critical for synaptic development and glutamatergic signaling, yet their role in attention deficit hyperactivity disorder (ADHD) remains poorly understood. This study examined serum levels of Thrombospondin-1 (Tsp-1), Sparc, and Sparcl-1 in children with ADHD and explored their associations with behavioral symptoms, executive dysfunction, and social impairments. Eighty-six children aged 6-12 years participated: 46 medication-naive with ADHD and 40 age- and sex-matched neurotypical controls. Clinical measures included the Conners' Parent Rating Scale-Revised: Long Form (CPRS-R:L), Social Responsiveness Scale (SRS), and Behavior Rating Inventory of Executive Function (BRIEF). Serum levels of Tsp-1, Sparc, and Sparcl-1 were quantified via ELISA. Children with ADHD exhibited significantly lower serum levels of Tsp-1 (p < 0.001), Sparc (p = 0.020), and Sparcl-1 (p = 0.049) than controls. Lower Sparc levels were associated with poorer executive functioning and reduced social responsiveness, while lower Tsp-1 levels were positively associated with higher ADHD symptom severity. This study provides the first evidence of reduced serum astrocyte-derived ECM proteins in children with ADHD, implicating glia-mediated synaptic dysregulation in the disorder's pathophysiology. These findings suggest a novel glia-centered mechanism and support the potential of ECM proteins as biomarkers for ADHD subtypes and as targets for future therapeutic interventions.