A Prospective Assessment of Lead, Methylmercury, and Prepulse Inhibition Deficits: The Early Life Exposures in Mexico to Environmental Toxicants Birth Cohort

Abstract

Lead and Methylmercury are environmental neurotoxicants known to interfere with neurodevelopment. Some neurodevelopmental consequences associated with lead and methylmercury exposure include intellectual deficits, behavioral and motor deficits, and impaired visuospatial performance. Several neuronal circuits associated with cognitive function and neurodevelopment can be probed with simple physiological behavioral paradigms, potentially serving as a marker of neurotoxicant effects. One such paradigm is pre-pulse inhibition (PPI), a sensorimotor gating process that indicates adequate organization of human cognitive processes. PPI deficits have been proposed as a neurobiological marker for pathologies indicative of inadequate motor or sensory gating such as observed in psychosis, schizophrenia, and other neurodevelopmental disorders. Although PPI’s relevance for neurodevelopmental disorders has been established in clinical, cross-sectional settings, its relationship with environmental neurotoxicants has not been epidemiologically explored. Additionally, PPI’s potential utility as a biomarker of neurotoxicant effects has not been established. Yet, by probing underlying neurobiology, PPI offers the potential to identify neurological deficits associated with neurotoxicants earlier and more objectively than current methods in environmental epidemiology. To our knowledge, no studies have examined the association between heavy metals and PPI deficits in human populations. We aimed to evaluate the utility of PPI as a biomarker of neurotoxicant effects by 1) identifying socio-demographic predictors of PPI using a data-driven prediction model, 2) estimating the causal effect of prenatal lead exposure on PPI deficits, and 3) estimating the association between methylmercury exposure and PPI deficits in children and adolescents 8-17 years of age using the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) birth cohort. In this body of work, we identified new predictors of PPI, found that prenatal lead may cause PPI deficits, and found an association between methylmercury exposure and PPI deficits. Our results suggest that PPI may be useful as an objective biomarker of neurotoxicant effects and an adjunct screening tool for neurodevelopmental disorders associated with sensory gating deficits.