Assessing Stable Characteristics of Endocrine Function Among Boys and Girls with Prenatal Alcohol Exposure as a Novel Clinical Tool

作为一种新的临床工具评估产前酒精暴露的男孩和女孩内分泌功能的稳定特征

基本信息

批准号：
10475102
负责人：
Kristina Andrea Uban
金额：
$ 17.87万
依托单位：
UNIVERSITY OF CALIFORNIA-IRVINE
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-19 至 2023-08-31
项目状态：
已结题

项目摘要

Individuals affected by prenatal alcohol exposure (PAE) can present with a complex profile of cognitive, behavioral, physical, and mental health problems, referred to as fetal alcohol spectrum disorder (FASD). Of particular relevance, up to 90% of individuals with FASD may experience mental health problems over the life course. Animal models of PAE demonstrate that alterations in neuroendocrine function serve as a fundamental neurobiological mechanism for increased mental health problems; thus, improving or normalizing endocrine function may provide a novel approach for improving outcomes. The primary aim of the K01 proposal is to accelerate the candidate's learning opportunities to addresses this translational gap in knowledge through examination of individual differences in endocrine activity in humans with PAE, and their implications for susceptibility for mental health problems. Towards this end, the candidate's unique and independent aims capitalize on 2 independent NIH-funded research programs: 1) 550 adolescents (33% PAE; 33% non-PAE with drinking moms; 33% non-PAE with non-drinking moms; 50% girls; aged 9-12 years) from the Adolescent Brain Cognitive Development (ABCD) study in the United States, and 2) 160 adolescents (50% PAE across all trimesters; 50% non-PAE; 50% girls; aged 9-12 years) as part of the Prenatal Alcohol SIDS and Stillbirth (PASS) birth cohort in South Africa. The K01 proposes to: A) utilize funded neuroimaging and prenatal substance exposure data in ABCD/PASS; B) utilize funded ABCD data on hormones, puberty and mental health; and C) collect new PASS data on hormones, puberty and mental health. Methods for assessing brain, mental health, and puberty will be harmonized between ABCD and PASS cohorts, yet there will be distinctly different experimental designs, each with their unique strengths and limitations. These contrasting cohort designs and populations provide a rare opportunity for acceleration of learning opportunities as well as advancement of our ability to identify the most important components of variance for understanding individual differences in endocrine function in adolescents with PAE. Groups will be matched on age, sex, race and SES within their respective cohorts. Initial findings from the ABCD cohort will inform tests in the independent PASS sample, providing strength for interpreting generalizability of findings across diverse social, racial and cultural environments. The candidate's training will take advantage of the rich expertise of the diverse mentoring team to integrate central/peripheral measures of endocrine function, by bridging the fields of neuroimaging, neuroendocrinology, salivary biosciences and biostatistics to better understand individual differences in endocrine function. The training plan capitalizes on the central location of CHLA, and includes didactic courses and one-on-one mentoring at USC (latent state trait modeling course), UCI (salivary bioscience course), and UCLA (MPlus). The training plan will foster new neuroimaging expertise through learning how to integrate two imaging modalities, as well as building expertise in salivary biosciences, biostatistics and mental health.

受产前酒精暴露 (PAE) 影响的个体可能会出现复杂的认知、行为、身体和心理健康问题，称为胎儿酒精谱系障碍 (FASD)。的特别相关的是，高达 90% 的 FASD 患者一生中可能会遇到心理健康问题课程。 PAE 动物模型表明，神经内分泌功能的改变是 PAE 的基本机制。增加心理健康问题的神经生物学机制；因此，改善或正常化内分泌功能可能提供一种改善结果的新方法。 K01提案的主要目的是加速候选人的学习机会，通过以下方式解决知识转化差距检查患有 PAE 的人类内分泌活动的个体差异及其对容易出现心理健康问题。为此，候选人独特且独立的目标利用 2 个由 NIH 资助的独立研究项目：1) 550 名青少年（33% PAE；33% 非 PAE）喝酒的妈妈们；不饮酒的妈妈中有 33% 的人没有发生 PAE； 50%是女孩； 9-12岁）来自青少年大脑美国的认知发展 (ABCD) 研究，以及 2) 160 名青少年（所有青少年的 PAE 占 50%）三个月； 50% 非 PAE； 50%是女孩； 9-12 岁）作为产前酒精 SIDS 和死产的一部分 (PASS) 南非出生队列。 K01 建议：A) 利用资助的神经影像和产前检查 ABCD/PASS 中的物质暴露数据； B) 利用资助的关于激素、青春期和心理的 ABCD 数据健康; C) 收集有关激素、青春期和心理健康的新 PASS 数据。评估大脑的方法， ABCD 和 PASS 队列之间的心理健康和青春期将是协调的，但会有明显的差异不同的实验设计，每种设计都有其独特的优点和局限性。这些对比鲜明的群体设计和人口为加速学习机会以及提高我们识别最重要的方差成分以了解个体的能力 PAE 青少年内分泌功能的差异。小组将根据年龄、性别、种族和社会经济地位进行匹配在各自的群体中。 ABCD 队列的初步结果将为独立 PASS 中的测试提供信息样本，为解释不同社会、种族和文化的研究结果的普遍性提供了力量环境。候选人的培训将利用多元化指导团队的丰富专业知识通过连接神经影像学领域来整合内分泌功能的中枢/外周测量，神经内分泌学、唾液生物科学和生物统计学，以更好地了解个体差异内分泌功能。培训计划利用 CHLA 的中心位置，包括教学课程以及 USC（潜在状态特征建模课程）、UCI（唾液生物科学课程）的一对一指导加州大学洛杉矶分校（MPlus）。该培训计划将通过学习如何整合两种神经影像学专业知识来培养新的神经影像学专业知识成像模式，以及建立唾液生物科学、生物统计学和心理健康方面的专业知识。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Structural white matter alterations in male adults with high functioning autism spectrum disorder and concurrent depressive symptoms; a diffusion tensor imaging study.

患有高功能自闭症谱系障碍并并发抑郁症状的男性成人的结构性白质改变；

DOI：
10.1016/j.jad.2019.08.010
发表时间：
2019-12-01
期刊：
Journal of affective disorders
影响因子：
6.6
作者：
B. Mohajer;M. Masoudi;Agaah Ashrafi;Esmaeil Mohammadi;Amir Sasan Bayani Ershadi;M. Aarabi;K. Uban
通讯作者：
K. Uban

A call to leverage a health equity lens to accelerate human neuroscience research.

呼吁利用健康公平视角加速人类神经科学研究。