Early-life lead exposure and neurodevelopmental disorders

Lead (Pb²⁺) exposure is a global public health problem of major proportion with an alarming number of children with blood Pb²⁺ levels > 10 >g/dL, twice the current CDC reference level for Pb²⁺ exposure. Mounting evidence from population-based studies suggests an association between chronic early life Pb²⁺ exposure (CELLE) and psychiatric disorders, specifically schizophrenia (SZ). Preclinical studies suggest a common mechanism in the pathophysiology of CELLE and SZ, NMDA receptor hypofunction. Here we describe human and experimental animal studies providing the evidence for such an association. Further, recent preclinical studies indicate that Pb²⁺-induced changes in neurotransmitter receptors that mediate the action(s) of drugs of abuse are increased in brain regions associated with addiction circuits in adolescence, a period of increased susceptibility to drug use and abuse and expression of psychiatric disease in humans. In summary, the relationship between the global burden of childhood Pb²⁺ exposure and the latent onset of psychiatric disorders and predisposition to drug use requires further investigations in human populations.