Steroid/thyroid hormones and inflammatory markers in adolescents with ADHD: comparisons with healthy controls and modifications by methylphenidate

Abstract

Background: Increasing evidence suggests that neuroendocrine and inflammatory mechanisms may contribute to attention-deficit/hyperactivity disorder (ADHD) pathophysiology, although findings in adolescents and the effects of methylphenidate (MPH) remain limited. Objective To quantify the baseline profile of activating hormones and levels of pro- and anti-inflammatory cytokines and their changes after treatment with methylphenidate (MPH) in adolescents with ADHD, in comparison with controls. Methods: Eighty-one adolescents (40 with ADHD and 41 healthy controls) were evaluated. Morning serum concentrations of cortisol, thyroid-stimulating hormone (TSH), dehydroepiandrosterone sulfate (DHEAS), S100B, and seven cytokines were measured. Patients with ADHD were reassessed after approximately four months of MPH treatment. Analyses considered ADHD presentation and oppositional defiant disorder (ODD) symptoms. Multivariable regression models were used to adjust biomarker associations for demographic and clinical variables. Results: Adolescents with ADHD showed significantly lower morning cortisol concentrations than controls. Several pro- and anti-inflammatory cytokines (IL-1β, IL-4, IL-5, IL-6, IL-10, and IL-13) were increased, particularly in males, whereas TNF-α and S100B did not differ between groups. Multivariable analyses confirmed independent associations between lower cortisol and higher cytokine levels with ADHD. TSH and DHEAS showed minor variations related to ODD symptoms but no consistent differences between ADHD presentations. MPH treatment improved clinical symptoms but produced no significant overall changes in hormonal or cytokine profiles Conclusion: Adolescents with ADHD exhibit an altered immune-hormonal profile characterized by reduced cortisol and increased circulating cytokines. These alterations appear largely independent of demographic and clinical confounders and only minimally influenced by short-term MPH treatment, suggesting persistent neuroendocrine-immune dysregulation during adolescence.