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

• 批准号: 10242897
• 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
• 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
• 来源: https://reporter.nih.gov/project-details/10242897
• 关键词: Acceleration; Address; Adolescent; Adrenal Glands; Adrenal hormone preparation; Affect; Age; Alcohols; Amygdaloid structure; Animal Model; Animals; Automobile Driving; Behavioral; Biological Sciences; Biometry; Birth; Blood Coagulation Factor VII; Brain; Brain region; Characteristics; Child; Clinical; Cognitive; Collection; Complex; Data; Drug Prescriptions; Endocrine; Environment; Estradiol; Exhibits; Experimental Designs; Feedback; Fetal Alcohol Exposure; Fetal Alcohol Spectrum Disorder; Fetal alcohol effects; Fostering; Functional Magnetic Resonance Imaging; Functional disorder; Funding; General Population; Gonadal Hormones; Hippocampus (Brain); Hormones; Human; Hydrocortisone; Hypothalamic structure; Individual; Individual Differences; Investigation; Knowledge; Learning; Life; Life Cycle Stages; Location; Magnetic Resonance Imaging; Measures; Mediating; Medical; Mental Health; Mentors; Methods; Modeling; Neuroendocrinology; Neurosecretory Systems; Norepinephrine; Outcome; Pattern; Peripheral; Pharmacologic Substance; Phenotype; Pituitary Gland; Population; Predisposition; Production; Provider; Proxy; Puberty; Race; Research; Rest; Role; Salivary; Sampling; Scanning; Seeds; South Africa; Structure; Sudden infant death syndrome; Testing; Testosterone; Time; Training; United States; United States National Institutes of Health; Youth; aged; base; behavioral health; boys; cognitive development; cohort; dehydroepiandrosterone; design; drinking; experience; fetal substance exposure; girls; imaging modality; improved; improved outcome; locus ceruleus structure; neurobiological mechanism; neuroimaging; novel; novel strategies; peer; physical conditioning; prenatal; programs; sex; social; stillbirth; stressor; tool; trait

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）影响的个体可能表现出复杂的认知， 行为，身体和精神健康问题，称为胎儿酒精谱系障碍（FASD）。的 特别相关的是，高达90%的FASD患者可能在一生中经历心理健康问题 当然了PAE的动物模型表明，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 功能可以提供一种新的方法来改善结果。K 01提案的主要目的是 加快候选人的学习机会，以解决这一知识转化的差距，通过 检查PAE患者内分泌活动的个体差异及其对 精神健康问题的易感性。为此，候选人的独特和独立的目标 利用2个独立的NIH资助的研究项目：1）550名青少年（33% PAE; 33%非PAE， 饮酒的母亲; 33%的非PAE与非饮酒的母亲; 50%的女孩;年龄9-12岁） 在美国的认知发展（ABCD）研究，以及2）160名青少年（50%的PAE在所有 妊娠期; 50%非PAE; 50%女孩; 9-12岁）作为产前酒精性SIDS和死产的一部分 （PASS）出生队列。K 01建议：A）利用资助的神经成像和产前检查 ABCD/PASS中物质暴露数据; B）利用受资助ABCD关于激素、青春期和精神 健康;和C）收集关于激素、青春期和心理健康的新PASS数据。用于评估脑的方法， 心理健康和青春期将在ABCD和PASS队列之间协调，但将有明显的 不同的实验设计，每个都有其独特的优势和局限性。这些对比鲜明的群体 设计和人口为加速学习机会提供了难得的机会， 提高我们的能力，以确定最重要的组成部分的差异，以了解个人 青少年PAE患者内分泌功能的差异。各组将根据年龄、性别、种族和社会经济地位进行匹配 在他们各自的队伍中。ABCD队列的初步发现将为独立PASS中的测试提供信息 样本，为解释不同社会，种族和文化的调查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辅导团队的丰富专业知识 整合内分泌功能的中枢/外周测量，通过桥接神经成像领域， 神经内分泌学、唾液生物科学和生物统计学，以更好地了解 内分泌功能培训计划利用了智利法律援助中心的中心位置，并包括教学课程 和一对一的指导在南加州大学（潜在状态特质建模课程），UCI（唾液生物科学课程），和 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方法来培养新的神经成像专业知识。 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。