Non-invasive skin trace elementomics reveals a characteristic pattern of essential element deficiency and toxic...

Attention-deficit/hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in childhood. Its clinical diagnosis primarily relies on behavioral assessments, lacking objective and non-invasive biological indicators. Trace elements are involved in neurotransmitter synthesis, myelin development, and prefrontal cortex function regulation, and their imbalance may be associated with the pathogenesis of ADHD. However, previous studies have mostly focused on single elements, lacking systematic evidence at the omics level. To analyze the differences in 30 skin element levels between children with ADHD and healthy controls, and to explore the associations of elemental imbalances with core symptoms, anxiety, and executive function, thereby providing a basis for non-invasive screening of childhood ADHD. A total of 549 children with ADHD and 963 healthy controls were enrolled. Skin element levels were measured using a non-invasive high-throughput technique. Behavioral assessments were performed using the CONNERS, SNAP‑IV, SCARED, and WEISS scales. Analysis of covariance (ANCOVA) with age as a covariate was used to compare intergroup differences in element levels. Partial correlation analysis was applied to control for age as a confounding factor. The Benjamini‑Hochberg method was used to control the false discovery rate (FDR) for multiple comparison correction, with a significance threshold of q < 0.05. After adjusting for age and FDR correction, 28 elements showed significant differences between the ADHD group and the control group. In the ADHD group, essential/potentially beneficial elements such as Mg, Zn, I, Cr, Li and Ge were decreased, whereas B and harmful elements including Pb, Hg, Cd, As, Al, Be, and Ba were increased. Multiple elements exhibited stable associations with inattention, hyperactivity-impulsivity, anxiety, and risk-taking behavior. Children with ADHD displayed a complex network pattern of synergistic and antagonistic inter-element relationships. Children with ADHD exhibit a characteristic skin trace elementomic imbalance, characterized by decreased beneficial elements and increased harmful elements, which is closely associated with behavioral symptoms. Non-invasive skin elementomics may serve as a reference indicator for population-based risk screening of childhood ADHD and holds promise for population-based screening.