Profile of Th1/Th2/Th17/Treg Signature Cytokines and Microglia Regulatory Cytokines in ADHD and Healthy Controls: A Neuroimmunological Approach

Background: Emerging evidence suggests that dysregulated immune homeostasis may play a role in the pathophysiology of ADHD; however, comprehensive profiling of T-helper (Th) cell subsets and microglial regulatory cytokines remains limited. Methods: This cross-sectional study included adolescents aged 12 to 18 years with ADHD ( n = 45) and healthy controls ( n = 41). Serum levels of Th1 (IL-12 and IFN-γ), Th2 (IL-4), Th17 (IL-17 and IL-23), Treg (IL-10 and TGF-β), and microglia regulatory cytokines (IL-34 and CSF-1) were measured by ELISA. ROC curve and logistic regression analyses were performed to determine the diagnostic and predictive value of the parameters in distinguishing ADHD. Results: Significant increases in IL-12, IL-17, IL-23, IL-4, and IL-10 levels were observed in the ADHD group compared to the control group. IL-12 and IL-17 showed the highest diagnostic yield (AUC = 0.77). IL-12 remained a strong independent predictor in multivariate analysis (OR = 55.88, P = .015). IFN-γ and TGF-β did not differ significantly between the groups. CSF-1 levels did not differ between the groups, while IL-34 showed an increase that approached statistical significance in the ADHD group ( P = .052; AUC = 0.622). Conclusions: Our results reveal a profile of Th1/Th17-dominated proinflammatory activation, partially compensatory Th2/Treg modulation, and potentially IL-34-mediated microglial divergence in ADHD. IL-12 and IL-17 showed the highest discriminatory performance; however, their AUC values (~0.77) remained at a moderate level. Our findings highlight the need for multidimensional immunophenotyping and point toward novel immune-targeted therapeutic strategies.