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在较长时间内经历一系列复杂的过程，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物质有关的长期行为发病率仍不确定。我们还缺乏直接解剖证据的数据，表明低水平暴露于已知的发育神经毒物会导致神经损伤。关于基因型差异如何在神经发育疾病中作为加重或保护因素发挥作用，我们知之甚少。在儿童环境健康领域，从未有过系统的尝试：1)确定早期暴露对成年后行为的影响；2)识别可能导致持续损伤的特定神经解剖学基础和生理过程，以及它们在行为中的神经心理学关联；3)评估参与神经递质分子功能的编码蛋白基因与环境暴露在神经解剖异常和行为问题表达中的相互作用。在这项研究中，我们将研究产前和产后暴露于铅（Pb）、同时暴露于锰与无创磁共振成像光谱（MRI/MRS）测量的神经解剖异常、成人注意缺陷多动障碍（A-ADHD）及其相关合并症以及20多岁受试者的犯罪行为之间的关系。本研究的另一个目的是在与中枢神经系统多巴胺能和血清素能功能相关的基因型差异的背景下检查这些剂量-反应关系。这项拟议的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。辛辛那提先导研究（CIS）队列主要是非裔美国人，具有社会经济劣势的历史。在最初的305名研究对象中，我们继续追踪大约250名20岁出头的人。从妊娠早期到17岁，对血液中的铅暴露进行了连续评估。我们将使用一种创新的核磁共振衍生生物标志物来评估血液和大脑中同时暴露的锰，作为铅对神经行为的长期影响的可能调节剂。有一个丰富的数据库，涵盖了这群人的寿命、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.