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

描述（由申请人提供）：中枢神经系统的成熟需要一系列复杂的过程，持续很长一段时间，使该器官特别容易受到环境影响。与产前和产后暴露于环境化学品相关的长期行为发病率仍然不确定。我们也缺乏直接的解剖学证据的神经损伤所造成的低水平暴露于已知的发育神经毒物的数据。关于基因型变异如何在神经发育疾病中起加重或保护因素的作用，我们的信息很少。在儿童的环境健康领域，从来没有一个系统的尝试：1）确定早期暴露对成年后期行为的影响; 2）确定可能造成持续损害的特定神经解剖学基质和生理过程，以及它们在行为中的神经心理学相关性;和3）评估编码涉及神经递质分子功能的蛋白质的基因与神经解剖学异常表达中的环境暴露之间的相互作用，和行为问题。在这项研究中，我们将研究产前和产后暴露于铅（Pb），同时暴露于锰和神经解剖异常测量非侵入性使用磁共振成像光谱（MRI/MRS），成人注意力缺陷多动障碍（A-ADHD）和相关的共病以及犯罪行为在他们的20多岁的主题之间的关系。本研究的另一个目的是在中枢神经系统中与多巴胺能和多巴胺能功能相关的基因型变异的背景下检查这些剂量-反应关系。这项研究建立在一项长期的前瞻性研究的基础上，该研究从1979年开始在产前招募受试者，并一直持续到今天。辛辛那提牵头研究（CIS）队列主要是具有社会经济劣势历史的非洲裔美国人。在305名受试者的初始队列中，我们继续跟踪大约250名20岁出头的受试者。铅暴露已连续评估血液中的头三个月至17岁。我们将使用一种创新的MRI衍生生物标志物评估血液和大脑中的锰暴露，作为铅对神经行为长期影响的可能修饰剂。有一个丰富的数据库，涵盖了队列的生命周期，医疗和社会历史。

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.