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

项目 2：青少年接触 BPA/邻苯二甲酸盐：认知

• 批准号: 8375029
• 负责人: SUSAN A KORRICK
• 金额: $ 5.37万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-12-01 至 2013-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8375029
• 关键词: Achievement; Address; Adolescence; Adolescent; Affect; Age; Animal Model; Animals; Anxiety; Area; Attention; Attention deficit hyperactivity disorder; Behavior; Behavior assessment; Behavioral; Birth; Brain; Brain Diseases; Brain region; California; Child; Child Development; Childhood; Cognitive; Data; Data Collection; Development; Exposure to; Gonadal Hormones; Gonadal Steroid Hormones; Growth; Growth and Development function; Human; Learning; Life; Longitudinal Studies; Measurement; Measures; Memory; Mental Depression; Metal exposure; Metals; Methods; Outcome; Parents; Performance; Pilot Projects; Population; Psychometrics; Puberty; Public Health; Research Infrastructure; Risk Factors; Rodent; Rodent Model; Role; Sampling; Schizophrenia; Short-Term Memory; Source; Symptoms; System; Testing; Toxic effect; Urine; Verbal Learning; Work; age effect; base; bisphenol A; boys; developmental disease; disability; executive function; girls; high risk; human data; insight; neurobehavior; neurobehavioral; neurodevelopment; novel; organochlorine exposure; phthalates; reproductive; research study; sex; sexual dimorphism; urinary; visual motor

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.

尽管人口普遍暴露于邻苯二甲酸盐和双苯酚A（BPA），并且证明了人类 神经发育可能会因其潜在的性腺激素破坏而改变，如果很少，如果 任何对这些暴露和神经发育的人类研究。青春期是脆弱性的关键时期 对性腺激素不仅深刻影响到生殖成熟度，还影响青少年 过渡到认知和行为成熟。这种青少年过渡的基础是大脑 组织发展和成长，包括在大脑区域的增长，证明了性二态性 可能与性腺类固醇作用有关。实际上，通常从青春期开始的脑部疾病，例如 精神分裂症可能部分反映了这些领域的不足发展。该试点项目的主要目的 是为了评估青少年对邻苯二甲酸酯和BPA与青少年神经行为的关系。这 提案是基于一项正在进行的纵向研究，对788名儿童自出生以来一直在 评估早期寿命污染物暴露（有机氯和金属）的关系 神经发育。该研究将使用该父母研究的既定基础设施（包括青少年 神经行为检查）和现有数据的财富，以解决2个新主题：（1）潜力 青少年邻苯二甲酸盐和BPA暴露的发育毒性，以及（2）鉴定青少年 神经行为结局可能对这些暴露敏感的基于：（a）的实验研究 性腺类固醇和大脑功能，（b）性能中性二态性的动物或人类证据，或 （c）与项目4的啮齿动物模型类比。新的数据收集将是尿液样本（在青少年，13 - 15年 神经行为测试）用于测量邻苯二甲酸酯和BPA代谢产物。这些暴露的关系 具有：视觉运动能力，语言能力，工作记忆，与 注意缺陷多动障碍（ADHD）和精神病症状（例如抑郁和焦虑）将 被评估。次要目的是评估邻苯二甲酸酯或BPA与 神经行为会因性别或青春期状态而异。将这项工作与项目4的平行动物进行比较 模型将在存在融合的地方会增加信心，发现观察到的影响实际上是暴露的 有关的。这将是最早洞悉这些化合物作为风险因素的作用的研究之一。 对于青春期的不良神经发育，暴露影响的高风险年龄以及一个年龄 适应不良的神经行为发育可能是实质性残疾的根源。