Abstract
BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, and recent research suggests systemic inflammation contributes to its pathophysiology. This study aimed to evaluate novel inflammatory markers-neutrophil-to-HDL ratio (NHR), lymphocyte-to-HDL ratio (LHR), monocyte-to-HDL ratio (MHR), platelet-to-HDL ratio (PHR), and systemic immune-inflammation index (SII)-in children with ADHD compared to healthy controls. Additionally, it assessed changes in these markers after 12 weeks of long-acting methylphenidate treatment and potential differences among ADHD subtypes. METHODS: This prospective study included 114 newly diagnosed, treatment-naive ADHD patients (aged 6-12) and 52 matched controls. Blood samples were obtained at baseline and after 12 weeks of treatment. Inflammatory markers were calculated from complete blood count and HDL levels. ADHD symptom severity was assessed using the Conners Parent Rating Scale-Revised: Short Form (CPRS-R:S), and anxiety and depression were measured with the Revised Child Anxiety and Depression Scale (RCADS). RESULTS: ADHD patients showed significantly elevated baseline levels of NHR, LHR, MHR, PHR, and SII compared to controls (Cohen's d range = 0.17-0.69). NHR independently predicted ADHD. Post-treatment, all inflammatory markers significantly decreased, suggesting a potential anti-inflammatory effect of methylphenidate (Cohen's d range = 0.17-0.91). Post-treatment LHR was higher in the combined ADHD subtype. CONCLUSIONS: This study underscores inflammation's role in ADHD and suggests these markers may reflect systemic inflammation in ADHD, but their clinical utility requires further investigation.