Serum metabolites and childhood-diagnosed ADHD: Prospective Cohort Study and Mendelian Randomization Analysis

Abstract ADHD, a neurological condition that onset in childhood is now an important part of the disease burden in the global population. ADHD is usually diagnosed at school age, and there are no authoritative research to articulate whether ADHD in adult shares a common pathogenic mechanism with ADHD in children. Previous studies have elucidated metabolic profiles as functional mediators, and the present study is the first to combine metabolomics and Mendelian randomization(MR) to elucidate the causal relationship between serum metabolites and ADHD diagnosed in children. A metabolomic study of childhood-diagnosed ADHD and normal children in a prospective cohort of preschoolers. Metabolomic results of preschool children enrolled in the cohort study identified 112 differential metabolites, with 69 metabolites upregulated and 43 metabolites downregulated. For MR studies, single nucleotide polymorphisms associated with childhood-diagnosed ADHD were identified from metabolite-wide association studies for IVW analysis. MR results revealed that the IVW approach revealed a total of 15 significant pathogenic association profiles from 486 metabolites, including 10 known metabolites and 5 unknown metabolites. Combining the results of MR analyses from metabolomic studies and cohort studies, arginine and α-tocopherol were two important metabolites affecting the diagnosis of ADHD in childhood. The metabolic pathways of primary bile acid biosynthesis and arginine/proline metabolism were the overlapping metabolic pathways in both studies.