Project 2: Adolescent Exposure to BPA/Phthalates: Cognitive & Behavioral

尽管人们普遍接触邻苯二甲酸盐和双酚A(BPA)，而且有证据表明，人类 神经发育可能会被性腺激素的潜在干扰所改变，如果 任何关于这些暴露和神经发育的人体研究。青春期是脆弱的关键时期 性腺激素不仅深刻地影响着生殖成熟的过渡，而且还影响着青春期 过渡到认知和行为成熟。这种青春期的转变背后隐藏着大量的大脑 组织的发展和成长，包括表现出性别二态的大脑区域的成长 可能与性腺类固醇效应有关。事实上，通常始于青春期的大脑障碍，例如 精神分裂症可能在一定程度上反映了这些区域的发育不足。这一试点项目的主要目的是 评估青少年接触邻苯二甲酸盐和双酚A与青少年神经行为的关系。这个 该提案基于一项正在进行的纵向研究，该研究对788名儿童进行了跟踪调查，这些儿童自出生以来一直处于 评估早期接触污染物(有机氯和金属)与随后的 神经发育。这项研究将使用这项家长研究的既定基础设施(包括青少年 神经行为检查)和丰富的现有数据来解决两个新主题：(1)潜在的 青少年邻苯二甲酸盐和双酚A暴露的发育毒性，以及(2)青少年的识别 神经行为结果可能对这些暴露敏感，其依据是：(A) 性腺类固醇和脑功能，(B)动物或人类表现出性别二态的证据，或 (C)与工程4‘S啮齿动物模型类比。新的数据收集将是尿样(13-15岁的青少年 神经行为测试)，用于测量邻苯二甲酸盐和双酚A代谢物。这些曝光之间的关系 用心理测量法测量：视觉运动能力，言语能力，工作记忆，与行为相关的 注意缺陷多动障碍(ADHD)和精神症状(如抑郁和焦虑)将 被评估。次要目标将是评估邻苯二甲酸酯或双酚A与 神经行为因性别或青春期状态而异。本工作与《S平行动物计划4》的比较 在存在趋同的情况下，模型将增加人们对所观察到的影响实际上是暴露的信心 相关的。这将是首批深入了解这些化合物作为危险因素的作用的研究之一。 对于青春期的不良神经发育，暴露影响的高危年龄，以及 适应不良的神经行为发育可能是导致严重残疾的原因之一。

Despite prevalent population exposure to phthalates and bisphenol A (BPA), and evidence that human neurodevelopment is likely to be altered by their potential disruption of gonadal hormones, there are few, if any, human studies of these exposures and neurodevelopment. Adolescence is a key period of vulnerability to gonadal hormones which profoundly affect not only transition to reproductive maturity, but also adolescent transition to cognitive and behavioral maturity. Underlying this adolescent transition is substantial brain organizational development and growth, including growth in brain regions demonstrating sexual dimorphisms likely related to gonadal steroid effects. In fact, brain disorders that typically start in adolescence, e.g. schizophrenia, may, in part, reflect deficient development in these areas. The primary aim of this pilot project is to assess the relation of adolescent exposure to phthalates and BPA with adolescent neurobehavior. The proposal builds on an ongoing longitudinal study of 788 children who have been followed since birth to assess the relation of early life contaminant exposures (organochlorines and metals) with subsequent neurodevelopment. The study will use this parent study's established infrastructure (including adolescent neurobehavioral exams) and wealth of existing data to address 2 new themes: (1) the potential developmental toxicities of adolescent phthalate and BPA exposures, and (2) the identification of adolescent neurobehavioral outcomes likely to be sensitive to these exposures based on: (a) experimental studies of gonadal steroids and brain function, (b) animal or human evidence of sexual dimorphism in performance, or (c) analogy with Project 4's rodent model. New data collection will be urine samples (at adolescent, 13-15 yrs neurobehavior testing) for measurement of phthalate and BPA metabolites. The relation of these exposures with psychometric measures of: visual motor abilities, verbal abilities, working memory, behaviors related to Attention Deficit Hyperactivity Disorder (ADHD), and psychiatric symptoms (e.g., depression and anxiety) will be assessed. Secondary aims will be assessment of the potential for associations of phthalates or BPA with neurobehavior to differ by sex or by pubertal status. Comparing this work with Project 4's parallel animal model will, where there is convergence, increase confidence that observed effects are, in fact, exposure related. This will be among the first studies to provide insight into the role of these compounds as risk factors for adverse neurodevelopment in adolescence, an age at high risk for exposure effects, and an age when maladaptive neurobehavioral development can be a source of substantial disability.