The Effects of Lead Exposure at Different Stages of Life on Neurobehavioral and Metabolic Outcomes.

Abstract

Lead exposure remains an enormous public health problem worldwide. In this dissertation, I investigated the effect of exposure to lead in terms of windows of exposures. With the methodological advantages of longitudinal study designs and the use of biomarkers for cumulative as well as short-term lead exposures, I aimed to establish the relationship between timing of exposure to lead and a variety of health outcomes. In the first project, I investigated the timing of perinatal and early childhood exposure to lead in relation to the psychobehavioral development in children aged from 6 to 13 years. The results did not show statistically significant associations between lead exposures in early life and the majority of behavioral outcomes. However, the findings suggested that exposure to lead in utero and during the first two years of life have strong impacts on inattention and hyperactivity behaviors in children. The goal of the second project was to understand the potential impact of lifetime exposure to lead on Parkinson’s disease development in subjects with genetic polymorphisms of the SNCA gene. Three loci were found strongly predicted Parkinson’s disease. Lead increased the odds of PD only among subjects who were genetically relatively resistant to the disease. This result implies that lead exposure and genetic predisposition in SNCA gene does not have a synergistic effect on PD development. The last project aimed to discover the relationship between lifetime lead exposure and risk of type 2 diabetes. It provided novel evidence that exposure to lead could result in type 2 diabetes. A significant finding was observed that increase in patella bone lead level was associated with higher risk of type 2 diabetes. A discrepancy between tibia lead and patella lead effects on development of type 2 diabetes was also observed. Our findings suggested that cumulative exposure to lead increases the risk of DM2 with a ceiling effect. The studies in this thesis provide a landscape of lead effects on human health across the life span with consideration of the timing of the exposures, and interactions with genetic vulnerabilities.