Brain Influences of Phthalates and Bisphenols in Adolescents

邻苯二甲酸盐和双酚对青少年大脑的影响

基本信息

批准号：
10180606
负责人：
Akhgar Ghassabian
金额：
$ 56.64万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-17 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10180606
关键词：
Adolescence Adolescent Affect Age Aggressive behavior Androgen Receptor Androgens Attention Attention deficit hyperactivity disorder Behavior Biological Birth Blood specimen Brain Cell Differentiation process Chemical Exposure Chemicals Child Childhood Cognition Complement Data Decision Making Development Diethylhexyl Phthalate Disinhibition Emotional Endocrine Disruptors Enrollment Environment Environmental Exposure Estrogens Executive Dysfunction Exposure to Failure Functional disorder Generations Goals Gonadal Steroid Hormones Growth Head circumference Hormonal Hormonal Change Hormones Impairment Impulsivity Intervention Life Life Cycle Stages Literature Long-Term Effects Magnetic Resonance Imaging Male Adolescents Measures Mediating Mothers Neuroglia Neuropsychology Parietal Lobe Participant Play Population Pregnancy Pregnant Women Problem behavior Process Regulation Risk-Taking Sample Size Sampling Short-Term Memory Structural defect Structure Testosterone Thick Thyroid Function Tests Thyroid Gland Thyroid Hormones Time Urine Work adolescent brain development androgenic brain morphology cohort early adolescence early childhood emerging adult executive function follow up assessment follow-up gray matter in utero myelination neurodevelopment neurogenesis neuroimaging neurotoxic neurotoxicity phthalates postnatal prenatal prenatal exposure response sex synaptic pruning thyroid disruption urinary white matter

项目摘要

Project Summary This proposal will leverage unprecedented data from a Dutch birth cohort to examine the influence of phthalate and bisphenol exposures in multiple potentially susceptible periods on executive function and behavior in adolescents. Substantial literature has investigated the negative impact of prenatal exposures to phthalates and bisphenols on developmental programming of cognition and behavior. Yet few studies have examined exposures beyond early childhood. Further, the rigor of earlier studies is limited due to the lack of focus on mechanisms and failure to apply a life course approach. We propose to measure urinary levels of phthalates and bisphenols at ages 9–10 and 13–14 years in ≈ 1000 participants of Generation R, the largest neuroimaging study in the general pediatric population enrolled prenatally with follow-up through adolescence. We will evaluate executive function and behavior in children at age 16–18 years and measure sex hormones. Available data on measures of chemicals during the prenatal period and at 5–6 years, thyroid function in both mother and child, brain magnetic resonance imaging at ages 9–10 and 13–14 years, and feasibility of follow-up during adolescence provide an exceptional opportunity to parse out neurotoxic effects of pre- and postnatal exposures and identify the mechanisms. The large sample size will allow assessing sex as a biological variable. Specific aims are 1) to determine the impact of prenatal, childhood, and early adolescent phthalate and bisphenol exposures on executive function and behavior in adolescents and 2) to examine potential mechanisms underlying adverse influences of phthalates and bisphenols including thyroid and sex hormone disruption as well as brain structural abnormalities and white matter integrity. We hypothesize that chemical exposures during childhood and adolescence are associated with impaired executive function and behavioral problems, independent of prenatal exposure. Perturbations of thyroid and sex hormones are hypothesized to partly explain this association. We expect to observe the impact of childhood and early adolescence exposures on parietal lobe, attention networks, and prefrontal and limbic tracts, independent of the global effect of prenatal chemical exposures. This proposal is grounded on evidence showing that significant growth and maturation of the adolescent brain occurs in response to hormonal changes. Our preliminary data show anti- androgenic effects of di-2-ethylhexylphthalate in adolescents and thyroid disruption by prenatal phthalate and bisphenol exposures. Because of similarities in exposure levels in this Dutch cohort and the US samples, findings of this study will be applicable to the US context. Understanding the neurotoxicity of phthalates and bisphenols during adolescence has high implications because the plasticity of the adolescent brain makes this period a time of considerable opportunity for intervention. If the adolescent brain is found to be affected by chemicals then guidance in regulations of chemical exposures beyond the prenatal period might be indicated.

项目摘要该建议将利用荷兰出生队列的前所未有的数据来检查邻苯二甲酸酯的影响在多个潜在的易感时期内对执行功能和行为的暴露于双酚青少年。大量文献研究了产前暴露对邻苯二甲酸盐的负面影响以及关于认知和行为发展编程的双酚。然而很少有研究检查超越童年的暴露。此外，由于缺乏关注机制和未能采用生命过程的方法。我们建议测量邻苯二甲酸酯的尿液水平在9-10岁和13-14岁的Bisphenols≈1000名参与者中，最大的参与者在普通小儿种群中的神经影像学研究通过青少年进行了产前招收。我们将评估16-18岁儿童的执行功能和行为，并衡量性激素。可用的有关产前时期化学品测量的数据，在5 - 6年时，甲状腺功能在两者中的功能母亲和儿童，在9-10岁和13-14岁时的脑磁共振成像以及随访的可行性在青少年期间，为解析产后和产后的神经毒性作用提供了极大的机会暴露并确定机制。大型样本量将允许评估性别作为生物学多变的。具体目的是1）确定产前，儿童和早期邻苯二甲酸盐的影响以及对青少年执行功能和行为的双酚暴露，以及2）检查潜力邻苯二甲酸盐和双苯酚（包括甲状腺和性激素）的不良影响的机制破坏以及大脑结构异常和白质完整性。我们假设该化学物质童年和青少年期间的暴露与执行功能和行为的受损相关问题，独立于产前暴露。假设甲状腺和性恐怖的扰动是部分解释了这种关联。我们希望观察童年和青少年早期暴露的影响在顶叶，注意网络以及前额叶和边缘区，与全球效应无关产前化学暴露。该提议基于证据，表明显着增长和青少年大脑的成熟是响应激素变化而发生的。我们的初步数据表明 DI-2-乙基苯甲酸酯在青少年和邻苯二甲酸酯和甲状腺破坏的雄激素作用和双酚暴露。由于该荷兰队列和美国样本的暴露水平相似，所以这项研究的发现将适用于美国的情况。了解邻苯二甲酸酯和青春期斑点期间的双酚具有很高的影响，因为青少年大脑的可塑性使得时期考虑干预的机会。如果发现青春期的大脑受到然后，可以指出化学药品对超出产前期限的化学暴露法规的指导。