Early Lead Exposure, ADHD & Persistent Criminality: Role of Genes and Environment

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DESCRIPTION (provided by applicant): The maturation of the central nervous system requires a complex sequence of processes over an extended period of time, making this organ particularly vulnerable to environmental influences. The long term behavioral morbidities associated with prenatal and postnatal exposures to environmental chemicals remain uncertain. We also lack data on direct anatomical evidence of neurological damage resulting from lower level exposures to known developmental neurotoxicants. We have very little information on how genotypic variances may function as exacerbating or protective factors in neurodevelopmental morbidity. In the area of children's environmental health there has never been a systematic attempt to 1) Determine the impact of early exposure on behavior in later adulthood; 2) Identify the specific neuroanatomical substrates and physiological processes that may have sustained damage as well as their neuropsychological correlates in behavior; and 3) Assess interactions between genes encoding proteins involved in neurotransmitter molecular functions and environmental exposures in the expression of neuroanatomical anomalies, and behavioral problems. In this study, we will examine the relationship between prenatal and postnatal exposure to lead (Pb), concurrent exposure to manganese and neuroanatomical anomalies measured non- invasively using magnetic resonance imaging the spectroscopy (MRI/MRS), adult attention deficit hyperactivity disorder (A-ADHD) and related co-morbidities as well as criminal behavior in subjects in their mid 20s. Another goal of this study is to examine these dose-response relationships in the context of genotypic variances related to dopaminergic and serotonergic function in the central nervous system. The proposed research builds on a longstanding prospective study of subjects recruited prenatally beginning in 1979 who continue to be followed today. The Cincinnati Lead Study (CIS) cohort is predominantly African- American with a history of socioeconomic disadvantages. Out of an initial cohort of 305 subjects we continue to track approximately 250 in their early 20s. Exposure to Pb has been assessed serially in blood from the first trimester to 17 years of age. We will be assessing concurrent Mn exposure in blood as well as in brain using an innovative MRI-derived biomarker as a possible modifier of lead's long lasting effects on neurobehavior. There is a rich database covering the cohort's lifespan medical and social histories.