Forever chemicals and mental health: A systematic review of per- and polyfluoroalkyl substances-related psychiatric outcomes and mechanistic insights

BACKGROUND Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants increasingly associated with adverse health outcomes, including psychiatric disorders. Although most research has focused on physiological toxicities, emerging evidence indicates that PFAS exposure may also disrupt central nervous system function - particularly among vulnerable populations such as children, adolescents, and pregnant women. AIM To answer the following two critical questions: What key findings regarding the impacts of PFAS exposure on psychiatric outcomes have emerged in the past five years? What research trends currently prevail in terms of methodologies, targeted populations, and mechanistic investigations? METHODS A systematic search guided by the PRISMA framework was conducted using Web of Science and Scopus, covering studies published between July 2021 and July 2025. Nineteen eligible studies were identified and thematically analyzed. RESULTS The article found increasing evidence linking PFAS exposure to psychiatric conditions, including depression, attention-deficit/hyperactivity disorder, autism spectrum disorder, and cognitive impairments. Proposed mechanisms include thyroid hormone disruption, neuroinflammation, and increased blood-brain barrier permeability. However, inconsistencies in findings - stemming from variability in exposure timing, PFAS compound types, and methodological approaches - remain a significant challenge. CONCLUSION Despite growing evidence of PFAS-related neuropsychiatric risks, current research is limited by methodological heterogeneity and incomplete mechanistic understanding. Future research should prioritize longitudinal designs, integrate multi-omics approaches, and refine exposure assessments. Urgent action is needed to incorporate scientific insights into public health policy, particularly for socioeconomically and environmentally vulnerable communities disproportionately exposed to PFAS.