Integrating genetics, neuroimaging, and environment in ADHD: a systematic umbrella review of meta-analytic evidence
Abstract
Abstract Background Attention-Deficit/Hyperactivity Disorder (ADHD) is a highly prevalent neurodevelopmental disorder with complex biological underpinnings involving genetic, neuroimaging, and environmental factors. Despite extensive research, a unified quantitative synthesis integrating these domains remains limited. Methods A systematic umbrella review was conducted following PRISMA 2020 guidelines. Four databases (PubMed, Web of Science, Scopus, PsycINFO) were searched up to March 2026. Eligible studies were meta-analyses or mega-analyses reporting quantitative effect sizes related to ADHD biological mechanisms. This review was not prospectively registered in a public database (e.g., PROSPERO). Results Ten high-quality studies encompassing over 4.6 million participants were included. ADHD demonstrated high heritability (h 2 ≈ 0.74), with a notable gap between twin-based and SNP-based estimates. Neuroimaging findings revealed consistent but modest structural and functional alterations, particularly in fronto-striatal and default mode networks. Environmental factors, including prenatal tobacco exposure, lead, and air pollution, showed significant associations with ADHD risk. Conclusions ADHD arises from the interaction of polygenic vulnerability and environmental exposures, converging on catecholaminergic dysregulation in fronto-striatal circuits. While genetic and neuroimaging markers show small individual effects, environmental factors present modifiable targets for prevention. These findings support a unified multi-level biological model of ADHD.