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Early Life Stress and Immune Dysfunction in Post-Institutionalized Adolescents

收容后青少年的早期生活压力和免疫功能障碍

基本信息

批准号：
9229564
负责人：
CHRISTOPHER L COE
金额：
$ 19.1万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-02-19 至 2019-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9229564
关键词：
17 year old Abnormal Cell Address Adolescence Adolescent Adopted Adoption Adrenal Glands Adult Affect American Animal Model B-Lymphocytes Behavioral Biology Bioperiodicity Blood Circulation Blood specimen Brain C-reactive protein CD28 gene CD3 Antigens CD8-Positive T-Lymphocytes Caring Cells Child Child health care Childhood Circadian Rhythms Color Complete Blood Count Country Cultured Cells Data Development Diagnostic tests Eastern Europe Endotoxins Event Family Feedback Goals Health Hormones Human Hydrocortisone Hypothalamic structure Immune Immune System Diseases Immune System and Related Disorders Immune Targeting Immune response Immune system Immunity Immunocompetence Immunology procedure Immunophenotyping Impaired health In Vitro Individual Infant Infection Inflammatory Institution Institutionalized Adolescent Intervention Learning Life Life Stress Link Literature Longevity Lymphocyte Lymphocyte Subset Measures Mediating Mental Health Mononuclear Neurosecretory Systems Orphanages Parents Pattern Phase Phenotype Pituitary Gland Population Preventive care Principal Investigator Public Health Recording of previous events Recovery Research Resources Risk Russia Saliva Sample Size Severities Shapes Signal Transduction Stress System T cell differentiation T-Lymphocyte Teenagers Testing UNICEF Variant Work Youth abuse neglect adopted child base cytokine deprivation directed attention experience immune function immune health immunoreaction immunoregulation improved infancy innovation neglect preclinical study prenatal prevent programs public health relevance resilience response trafficking

项目摘要

DESCRIPTION (provided by applicant): There is a dearth of evidence in humans definitively showing that stress confined to the prenatal-infancy period has programming-like effects on the immune system. In addition, human studies of immune correlates of adverse childhood conditions have not focused specifically T-cell phenotypes involved in immune regulation that may compromise the ability to respond to infection. Both of these gaps in the literature are highly significant in that they limit our ability to understand the mechanisms through which early life stress (ELS) impairs health across the life span. This R21 addresses these lacunae by conducting sophisticated immunophenotyping and functional immune assays in a unique population of youth (14 through 17 years of age) who as infants (< 36 months) were adopted from orphanages/institutions in Russia/Eastern Europe into well-resourced and generally stable, low-life-stress families in the US. The early life stress (ELS) for these youth, thus, was confined to the prenatal-infancy period. There are two aims. Aim 1: Determine the impact of ELS on immune responses of these youth now that they are adolescents. Blood samples will be obtained from 30 post-institutionalized (PI) and 30 comparison adolescents. Sophisticated multi-color immunophenotyping will be used to characterize lymphocyte subsets and mononuclear cell responses will be probed in vitro with stimulants, and cytokine levels in supernatants determined with multi-cytokine arrays. Complete blood counts and C-reactive protein levels also will be determined. Saliva cortisol collected at testing will assess whether transient cortisol elevations in response to blood sampling contribute to the immune differences between groups. Aim 2. Delineate factors that account for differential vulnerability among ELS youth, including distorted hormone biorhythms and severity of the ELS. The second phase of this project will expand the sample size to include 30 additional PI's (total=60), providing sufficient diversity to determine the influence of the severity and duration of institutional care and the mediating influence of dysregulated HPA diurnal rhythms to predict variation in the T cell repertoire and cellular responses in stimulated cultures. This work is highly significant because, by focusing on youth who experience radical improvements in care post-infancy, it will provide the strongest evidence to date of prenatal-infancy programming-like effects on the human immune system and underscores the importance of preventing early deprivation and neglect. It also has potential significance for improving the preventive care of individuals with a history of early adverse care, by delineating specific immune alterations that may underlie potential health risks later in adulthood. It is highly innovative in being the first study of ELS in humans to employ such a sophisticated immune panel and to combine measures that are integral to a pro-inflammatory bias and immune competence. This R21 project will lay the groundwork for a new avenue of ELS-immune research that is focused on lingering sequelae of childhood experiences.