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

 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（由申请人提供）：皮质醇（CORT）是一种受下丘脑-垂体-肾上腺（HPA）轴调节的类固醇激素，是慢性应激和应激反应性的公认生物标志物。HPA轴功能是一个交叉的生理机制，与一系列精神，健康和社会结果（包括儿童认知）中的个体差异有关。反过来，儿童认知本身也是一种交叉机制，它是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的基础。先前的研究将CORT概念化为对环境压力和不利条件的反应，因为CORT长期升高与低社会经济地位（SES）相关，并部分介导SES-认知关联。然而，CORT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养育经历的反应改变了参与神经发育的基因的表达。这表明CORT也可能与遗传对儿童认知的影响相互作用，并且可能是先前研究中观察到的基因× SES相互作用的基础机制。本计画将利用生物统计学与分子遗传学的方法，探讨基因、SES、CORT与儿童认知之间的关系。我们将招募700对同性双胞胎（50%同卵，总N = 1400名儿童）的不同样本，从两个主要大都市地区的公立学校名册中确定3-5年级。将从许多来源收集多种方法的数据，包括（a）家长和儿童的调查答复;（B）实验室认知和成绩测试;（c）累积的个人教育记录，包括学校成绩和州规定的成绩测试成绩;（d）州和联邦机构关于社区环境和学校质量的行政数据;（e）实验室内皮质醇反应性和对急性社会心理应激的恢复;（f）在家中对皮质醇昼夜节律的重复评估;（g）头发中累积的皮质醇水平;（h）唾液DNA样本，我们将对生物CORT通路中的多态性进行基因分型。结合行为遗传学、基因型、教育、内分泌和人口统计学数据，我们将能够（1）使用双胞胎和测量基因方法，通过多种CORT输出指标来检查HPA轴功能的遗传病因;（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以及CORT通路中的遗传多态性是否与双胞胎模型（基因×激素和基因×基因相互作用）中估计的对认知的潜在遗传影响相互作用。这个创新的跨学科项目将在理解HPA轴功能个体差异的病因及其与儿童社会经济劣势和认知发展的关系方面开辟新的天地。