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，是一种公认​​的慢性应激和应激反应性的生物标志物。与一系列精神病学、健康和社会结果（包括儿童认知）的个体差异相关的生理机制，反过来，童年认知本身就是精神病学个体差异背后的交叉机制。先前的研究将 CORT 概念化为对环境压力和不利条件的反应，因为长期升高的 CORT 与低社会经济地位 (SES) 相关，并部分调节 SES 认知关联。此外，动物研究发现，糖皮质激素对早期应激养育经历的反应会改变参与神经发育的基因的表达，这表明 CORT 也可能与儿童的遗传影响相互作用。认知，并且可能是先前研究中观察到的基因与 SES 相互作用的基础机制。该项目将使用生物识别和分子遗传学方法来研究基因、SES、CORT 和儿童认知之间的关系。我们将招募 700 个不同的样本。从两个主要大都市地区的公立学校名册中确定的 3-5 年级同性双胞胎（50% 同卵双胞胎，总数 = 1400 名儿童）将通过多种来源收集，包括： (a) 家长和儿童调查答复； (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表现； (d) 来自州和联邦的行政数据；社区环境和学校质量方面的机构；(e) 针对急性社会心理压力源的实验室皮质醇反应和恢复；(f) 反复在家中评估皮质醇昼夜节律；(g) 头发中累积的皮质醇水平；八）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。行为遗传、基因型、教育、内分泌和人口统计数据的结合将使我们能够 (1) 检查 HPA 轴功能的遗传病因学，如索引所示。使用双胞胎和测量基因方法对 CORT 输出进行多种测量；（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 以及遗传多态性是否存在正如在孪生模型（基因×激素和基因×基因相互作用）中估计的那样，这一创新的跨学科项目将在理解 HPA 轴功能个体差异的病因学方面开辟新的领域。及其与儿童社会经济劣势和认知发展的关系。