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

• 批准号: 10656546
• 负责人: Akhgar Ghassabian
• 金额: $ 60.69万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 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/10656546
• 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; Predisposition; 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 magnetic resonance imaging; brain morphology; cohort; early adolescence; early childhood; emerging adult; empowerment; 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

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 这项建议将利用荷兰出生队列中史无前例的数据来检查邻苯二甲酸盐的影响 和双酚暴露在多个潜在易感期对执行功能和行为的影响 青少年。大量文献研究了产前接触邻苯二甲酸盐的负面影响。 和双酚类物质对认知和行为发展规划的影响。然而，很少有研究研究 暴露在儿童早期以外的地方。此外，由于缺乏对以下问题的关注，早期研究的严谨性有限 机制和未能应用生命过程方法。我们建议测量尿液中邻苯二甲酸酯的水平 和双酚类物质在9-10岁和13-14岁的≈1000名R代参与者中是最大的 一般儿科人群的神经影像研究在产前登记，并在青春期进行随访。 我们将评估16-18岁儿童的执行功能和行为，并测量性激素。 关于产前和5-6年期间的化学物质测量的现有数据，两者的甲状腺功能 9-10岁和13-14岁母亲和儿童的脑磁共振成像，以及随访的可行性 在青春期提供了一个特殊的机会来分析出生前和出生后的神经毒性影响 暴露并确定其机制。大样本量将允许将性别作为一种生物学评估 变量。具体目标是1)确定产前、儿童期和青春期早期邻苯二甲酸盐的影响 和双酚暴露对青少年执行功能和行为的影响以及2)检查潜力 邻苯二甲酸酯和包括甲状腺和性激素在内的双酚类物质的不良影响机制 以及大脑结构异常和白质完整性。我们假设这种化学物质 儿童期和青春期暴露与执行功能和行为受损有关 问题，与产前暴露无关。甲状腺激素和性激素的紊乱被认为是 这部分解释了这种联系。我们希望观察儿童期和青春期早期暴露的影响 在顶叶、注意网络、前额叶和边缘束上，独立于 产前接触化学物质。这一提议的依据是有证据表明，显著的增长和 青春期大脑的成熟是对荷尔蒙变化的反应。我们的初步数据显示， 邻苯二甲酸二乙基己酯对青少年的促雄激素作用和产前邻苯二甲酸二乙基己酯对甲状腺的干扰 暴露在双酚环境中。由于这一荷兰队列和美国样本的接触水平相似， 这项研究的结果将适用于美国的情况。了解邻苯二甲酸酯的神经毒性和 青春期的双酚类物质具有很高的意义，因为青春期大脑的可塑性使 这是一个相当有机会进行干预的时期。如果青少年的大脑被发现受到 然后，可能需要对超过产前阶段的化学品暴露法规进行指导。

项目成果

Gender Diversity and Brain Morphology Among Adolescents.

• DOI: 10.1001/jamanetworkopen.2023.13139
• 发表时间: 2023-05-01
• 期刊: JAMA network open
• 影响因子: 13.8

Prenatal phthalate exposure and fetal penile length and width.

产前邻苯二甲酸盐暴露与胎儿阴茎长度和宽度。

• DOI: 10.1038/s41390-023-02939-x
• 发表时间: 2023
• 期刊: Pediatric research
• 影响因子: 3.6
• 作者: Salvi,NicoleB;Ghassabian,Akhgar;Brubaker,SaraG;Liu,Hongxiu;Kahn,LindaG;Trasande,Leonardo;Mehta-Lee,ShilpiS
• 通讯作者: Mehta-Lee,ShilpiS

Determinants of phthalate exposures in pregnant women in New York City.

• DOI: 10.1016/j.envres.2022.113203
• 发表时间: 2022-09
• 期刊: ENVIRONMENTAL RESEARCH
• 影响因子: 8.3
• 作者: Liu, Hongxiu;Wang, Yuyan;Kannan, Kurunthachalam;Liu, Mengling;Zhu, Hongkai;Chen, Yu;Kahn, Linda G.;Jacobson, Melanie H.;Gu, Bo;Mehta-Lee, Shilpi;Brubaker, Sara G.;Ghassabian, Akhgar;Trasande, Leonardo
• 通讯作者: Trasande, Leonardo

Prenatal Exposure to Nonpersistent Chemical Mixtures and Offspring IQ and Emotional and Behavioral Problems.

产前接触非持久性化学混合物与后代智商以及情绪和行为问题。

• DOI: 10.1021/acs.est.1c04455
• 发表时间: 2021
• 期刊: Environmental science & technology
• 影响因子: 11.4
• 作者: vandenDries,MichielA;Ferguson,KellyK;Keil,AlexanderP;Pronk,Anjoeka;Spaan,Suzanne;Ghassabian,Akhgar;Santos,Susana;Jaddoe,VincentWV;Trasande,Leonardo;Tiemeier,Henning;Guxens,Mònica
• 通讯作者: Guxens,Mònica