Cortisol, Socioeconomic Status, and Genetic Influences on Cognitive Development

皮质醇、社会经济地位和遗传对认知发展的影响

• 批准号: 9030328
• 负责人: Elliot Max Tucker-Drob
• 金额: $ 66.25万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9030328
• 关键词: Academic achievement; Achievement; Acute; Animal Experimentation; Architecture; Area; Behavioral Genetics; Biological; Biological Markers; Biometry; Child; Childhood; Chronic; Chronic stress; Circadian Rhythms; Cognition; DNA; Data; Development; Dimensions; Disadvantaged; Educational Status; Endocrine; Environment; Etiology; Gene Expression; Genes; Genetic; Genetic Polymorphism; Genetic Predisposition to Disease; Genetic Suppression; Genetic screening method; Genotype; Glucocorticoids; Hair; Health; Home environment; Hormones; Human; Hydrocortisone; Individual; Individual Differences; Inequality; Intervention; Laboratories; Learning; Link; Longevity; Measures; Mediating; Mediator of activation protein; Mental disorders; Methodology; Methods; Modeling; Molecular Genetics; Neighborhoods; Outcome; Output; Parents; Pathway interactions; Performance; Phenotype; Physiological; Policies; Population Control; Quantitative Genetics; Records; Recovery; Recruitment Activity; Research; Research Personnel; Saliva; Salivary; Same-sex; Sampling; Schools; Skin; Social Environment; Socioeconomic Status; Source; Staging; Stratification; Stress; Surveys; Testing; Texas; Tissues; Twin Multiple Birth; achievement test; austin; biological adaptation to stress; cognitive ability; cognitive development; cognitive performance; design; elementary school; endophenotype; experience; gene interaction; genetic approach; genetic information; genome-wide; human capital; hypothalamic-pituitary-adrenal axis; indexing; innovation; low socioeconomic status; metropolitan; neurodevelopment; physical conditioning; programs; psychologic; psychosocial; public health relevance; response; social; socioeconomic disadvantage; socioeconomic disparity; steroid hormone; stress reactivity; stressor; theories; time interval; Academic achievement; Achievement; Acute; Animal Experimentation; Architecture; Area; Behavioral Genetics; Biological; Biological Markers; Biometry; Child; Childhood; Chronic; Chronic stress; Circadian Rhythms; Cognition; DNA; Data; Development; Dimensions; Disadvantaged; Educational Status; Endocrine; Environment; Etiology; Gene Expression; Genes; Genetic; Genetic Polymorphism; Genetic Predisposition to Disease; Genetic Suppression; Genetic screening method; Genotype; Glucocorticoids; Hair; Health; Home environment; Hormones; Human; Hydrocortisone; Individual; Individual Differences; Inequality; Intervention; Laboratories; Learning; Link; Longevity; Measures; Mediating; Mediator of activation protein; Mental disorders; Methodology; Methods; Modeling; Molecular Genetics; Neighborhoods; Outcome; Output; Parents; Pathway interactions; Performance; Phenotype; Physiological; Policies; Population Control; Quantitative Genetics; Records; Recovery; Recruitment Activity; Research; Research Personnel; Saliva; Salivary; Same-sex; Sampling; Schools; Skin; Social Environment; Socioeconomic Status; Source; Staging; Stratification; Stress; Surveys; Testing; Texas; Tissues; Twin Multiple Birth; achievement test; austin; biological adaptation to stress; cognitive ability; cognitive development; cognitive performance; design; elementary school; endophenotype; experience; gene interaction; genetic approach; genetic information; genome-wide; human capital; hypothalamic-pituitary-adrenal axis; indexing; innovation; low socioeconomic status; metropolitan; neurodevelopment; physical conditioning; programs; psychologic; psychosocial; public health relevance; response; social; socioeconomic disadvantage; socioeconomic disparity; steroid hormone; stress reactivity; stressor; theories; time interval

 DESCRIPTION (provided by applicant): Cortisol (CORT), a steroid hormone that is regulated by the hypothalamic-pituitary-adrenal (HPA) axis, is a well-established biomarker for chronic stress and stress reactivity. HPA axis function is a cross-cutting physiological mechanism linked to individual differences in an array of psychiatric, health, and social outcomes, including childhood cognition. Childhood cognition, in turn, is itself a cross-cutting mechanism underlying individual differences in psychiatric disorders, physical health, and human capital across the lifespan. Previous research has conceptualized CORT as a response to environmental stress and disadvantage, as chronically elevated CORT is associated with low socioeconomic status (SES) and partially mediates the SES-cognition association. However, the genetic underpinnings of individual differences in CORT are poorly understood. Moreover, animal research has found that glucocorticoid responses to early stressful rearing experiences change the expression of genes involved in neural development. This suggests that CORT may also interact with genetic influences on child cognition, and may be a mechanism that underlies gene × SES interactions observed in previous research. This project will examine the relations between genes, SES, CORT, and childhood cognition using both biometric and molecular genetic approaches. We will recruit a diverse sample of 700 same-sex twin pairs (50% monozygotic, total N = 1400 children) in grades 3-5 identified from public school rosters in two major metropolitan areas. Multi-method data will be collected from numerous sources, including (a) parent and child survey responses; (b) in-laboratory cognition and achievement testing; (c) cumulative individual-level educational records with school grades and performance on state-mandated achievement tests; (d) administrative data from state and federal agencies on neighborhood context and school quality; (e) in-laboratory cortisol reactivity and recovery in response to an acute psychosocial stressor; (f) repeated in-home assessments of cortisol diurnal rhythm; (g) accumulated cortisol levels in hair, and (h) salivary DNA samples, which we will genotype for polymorphisms in the biological CORT pathway. This combination of behavioral genetic, genotypic, educational, endocrine, and demographic data will allow us to (1) examine the genetic etiology of HPA axis function, as indexed by multiple measures of CORT output, using both twin and measured-gene methodologies; (2) test the genetic and environmental mechanisms by which CORT output is associated with child cognition; (3) test whether CORT, as well as genetic polymorphisms in the CORT pathway, interact with latent genetic influences on cognition, as estimated in a twin model (gene × hormone and gene × gene interactions). This innovative and interdisciplinary project will break new ground in understanding the etiology of individual differences in HPA axis function and its relations to socioeconomic disadvantage and cognitive development in children.

 描述（由适用提供）：皮质醇（Cort）是一种类固醇猪，由下丘脑 - 垂体 - 肾上腺（HPA）轴调节，是慢性应激和压力反应性的良好生物标志物。 HPA轴功能是一种横切的物理机制，与一系列精神病，健康和社会成果（包括童年认知）的个体差异相关。反过来，童年认知本身就是一种跨切割机制，即整个生命周期中精神疾病，身体健康和人力资本的个体差异。先前的研究将Cort概念化为对环境压力和灾难的反应，因为长期升高的Cort与社会经济状况低下有关，并部分介导了SES认知协会。但是，科特个体差异的遗传基础知之甚少。此外，动物研究发现，糖皮质激素对早期压力饲养经历的反应改变了与神经发育有关的基因的表达。这表明Cort也可能与遗传对儿童认知的影响相互作用，并且可能是基因×SES相互作用的机制。该项目将使用生物识别和分子遗传学方法研究基因，SES，Cort和儿童认知之间的关系。我们将在从两个主要大都市地区的公立学校名册上确定的3 - 5年级中招募700个同性双胞胎（50％单卵，n = 1400名儿童）的潜水员样本。将从众多来源收集多方法数据，包括（a）父母和儿童调查答复； （b）实验室的认知和成就测试； （c）具有学校成绩的累积个人教育记录，并在国家规定的成就测试中表现出色； （d）在邻里和学校质量上来自州和联邦机构的行政数据； （e）响应急性社会心理压力源的实验室内皮质醇反应性和恢复； （f）对皮质醇昼夜节奏的重复评估； （g）头发中积累的皮质醇水平和（H）唾液DNA样品，我们将在生物学Cort途径中的多态性基因型。行为遗传，基因型，教育，内分泌和人口统计数据的这种组合将使我们能够（1）检查HPA轴功能的遗传病因，如使用双胞胎和测量的基因方法所用的多种CORT输出索引； （2）测试Cort输出与儿童认知相关的遗传和环境机制； （3）测试Cort途径中的Cort以及遗传多态性是否与潜在的遗传影响对认知的影响相互作用，如在Twin模型（基因×激素和基因×基因相互作用）中所述。这个创新和跨学科的项目将在理解HPA轴功能中个体差异及其与儿童社会经济灾难和认知发展的关系的病因方面奠定新的基础。