Relationship between PFAS and attention-deficit/hyperactivity disorder or autism spectrum disorder: Epidemiological and experimental evidence

Abstract

Per- and polyfluoroalkyl substances (PFAS) are widespread environmental contaminants found in various consumer products, such as drinking water, infant formula, and food, as well as in human biospecimens, including blood, urine, breastmilk, and cerebrospinal fluid. Previous evidence indicates that PFAS exposure poses significant neurotoxic risks, owing to their ability to penetrate the blood-brain barrier and bioaccumulate in neural tissue. The developing brains of fetuses and infants are particularly susceptible to the harmful effects of environmental pollutants because of their incomplete barrier and immune system development. This narrative review synthesizes current epidemiological and experimental evidence on the neurodevelopmental effects of PFAS exposure, with a primary focus on attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). The available data, from both cross-sectional and prospective cohort surveys, indicate a potential link between PFAS exposure and the development of ADHD or ASD. Additionally, experimental studies demonstrate that PFAS exposure disrupts neurotransmitter regulation, induces oxidative stress and chronic neuroinflammation, and alters gut microbiota, all of which reflect key pathological features observed in both clinical and preclinical models of ADHD and ASD. The present narrative review also discusses current challenges and research directions aimed at elucidating the causal links between PFAS insults and the onset of ADHD or ASD. Notably, this review highlights the need for molecular epidemiological approaches and realistic exposure models in animal research to deepen our understanding of causal associations.