Background <p>Neuronal pentraxin 2 (NPTX2), a synaptic protein regulating AMPA receptors and glutamate homeostasis, has been suggested as a biomarker of synaptic integrity in neurodegenerative and psychiatric disorders. This study investigated plasma NPTX2 levels in adults with ADHD and their associations with symptom severity and executive functioning.</p> Methods <p>In this cross-sectional case-control study, 79 medication- and comorbidity-free adults with ADHD and 70 matched typical controls were recruited. Participants underwent structured clinical interviews, standardized self-report scales on ADHD and comorbid anxiety/depression symptoms, and neurocognitive tests (Stroop, Wisconsin Card Sorting, Cancellation, Serial Digit Learning, Judgment of Line Orientation). Plasma NPTX2 levels were measured using ELISA. Between-group comparisons, correlation analyses, and multiple regressions adjusting for demographic and comorbid symptoms were conducted.</p> Results <p>Adults with ADHD showed significantly higher NPTX2 levels than controls, with a small effect size. Within the ADHD group, higher NPTX2 was negatively correlated with ADHD symptom severity, excessive mind wandering, and poorer performance on executive function tests (Stroop, Wisconsin Card Sorting, Cancellation). These correlations were not observed in controls. Regression analyses confirmed that the association between NPTX2 and ADHD symptoms remained significant after adjusting for age, gender, education, and anxiety/depression scores.</p> Conclusion <p>Elevated NPTX2 levels in adults with ADHD and their negative associations with symptom severity and executive dysfunction may suggest a potential compensatory neuroprotective role. NPTX2 may serve as a non-invasive biomarker reflecting synaptic processes in ADHD. Longitudinal and interventional studies are needed to clarify its temporal dynamics and clinical utility.</p>