Inflammatory cytokine alterations in autism spectrum disorder and attention-deficit/hyperactivity disorder: a...

Although autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) show significant clinical overlap, it remains unclear whether they share a common basis of immune dysregulation. To characterize the shared and distinct immune dysregulation, we performed a network meta-analysis (NMA) to compare inflammatory profiles across ASD, ADHD, and healthy controls (HC). We systematically searched PubMed, Web of Science, and Embase for literature published up to January 1, 2025. For each inflammatory marker, NMA was conducted when studies for both ADHD and ASD were available; otherwise, pairwise meta-analyses were used. Additionally, meta-regression analysis was employed to assess the influence of age and sex. Seventy-four studies were included (participants: ASD: 4331, ADHD: 990, HC: 5037). NMA showed that, compared with controls, individuals with ASD had higher levels of CRP, IL-6, IL-8, IL-1β, and BDNF, whereas individuals with ADHD had lower levels of TNF-α, IL-2, and MCP-1. Individuals with ASD had higher levels of TNF-α, IL-2, IL-8, IL-1β, and MCP-1 compared to those with ADHD. Pairwise meta-analysis revealed elevated levels of IL-4, IL-7, IL-12, IL-1α, MIP-1β, eotaxin, and GM-CSF in ASD, while no significant differences were observed between ADHD and controls. Pairwise meta-regression suggested that certain inflammatory markers may be influenced by age and sex. This first NMA suggests distinct immune dysregulation patterns: individuals with ASD exhibit alterations across multiple inflammatory cytokines, whereas individuals with ADHD show decreased levels of specific inflammatory factors. Future large-scale studies are needed to validate these biomarkers.