Fetal Antecedents to Depression and Risk for CVD

胎儿抑郁症的前因和心血管疾病的风险

• 批准号: 7585783
• 负责人: JILL M GOLDSTEIN
• 金额: $ 74.92万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-01-11 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7585783
• 关键词: 7 year old; Address; Adrenal Glands; Adrenal hormone preparation; Adult; Adult Children; Adverse effects; Affect; Affective; Age; Age-Years; Animals; Archives; Autonomic nervous system; Biological Assay; Birth; Blood; Blood Pressure; Brain region; C-reactive protein; California; Cardiac; Cardiovascular Diseases; Child health care; Comorbidity; Constitutional; Corticotropin; Data; Development; Disease; Disease Outcome; Etiology; Exposure to; Family; Fatty acid glycerol esters; Fetal Development; Fetal Growth Retardation; Gestational Age; Growth; Health; Heart; Height; High Density Lipoprotein Cholesterol; Hormonal; Hormones; Human; Hydrocortisone; Hypothalamic structure; Infant; Inflammatory; Inflammatory Response; Insulin; Interleukin-1 alpha; Interleukin-10; Interleukin-6; Interleukins; Intervention; LDL Cholesterol Lipoproteins; Leg; Length; Link; Literature; Major Depressive Disorder; Measures; Mediating; Mediator of activation protein; Modeling; Morbidity - disease rate; Mothers; New England; Outcome; Pathway interactions; Perinatal; Perinatal Exposure; Pituitary Gland; Polypeptide Hormones; Pre-Eclampsia; Pregnancy; Prevalence; Prevention; Recording of previous events; Recruitment Activity; Regulation; Reporting; Research; Research Personnel; Risk; Risk Factors; Sampling; Scheme; Series; Serum; Siblings; Socioeconomic Status; Stress; TNF gene; Testing; Third Pregnancy Trimester; Triceps Brachii Muscle; Tumor Necrosis Factor-alpha; Tumor Necrosis Factors; Variant; base; cardiovascular disorder risk; cohort; cost; cytokine; depression; design; disability; disorder risk; fasting glucose; fetal; fetal blood; hypothalamic-pituitary-adrenal axis; interest; maternal serum; mortality; offspring; polypeptide; prenatal; prevent; programs; response; sex; standing height; theories; waist circumference

DESCRIPTION (provided by applicant): In adulthood, there is a high comorbidity between major depressive disorder (MOD) and risk for cardiovascular disease (CVD), two of the leading causes of disability and mortality worldwide. This application will test hypotheses that there are shared prenatal antecedents to these disorders which will contribute to understanding their etiology and co-occurrence in adulthood. Research has demonstrated significant associations between cytokines (TNF-a, IL-1P, IL-6, CRP), HPA hormone abnormalities and MOD and CVD risk. Our hypotheses about fetal antecedents are based on evidence that some of the major brain regions involved in regulating affect are also involved in inflammatory responses, the HPA axis, and ANS which controls the heart's R-R interval variability (RRV) and blood pressure. We propose that HPA hormones and cytokines TNF-a, IL-1P, IL-6 that these shared brain regions express are the critical links between MOD and CVD risk, beginning during prenatal development. Our primary aims are to test for the: 1) association between elevated maternal-fetal cytokine levels and MOD & CVD risks; 2) associations between elevated maternal-fetal cytokines and adult offspring's HPA axis, cytokines TNF-a, IL-1(3, IL-6, CRP, and the heart's R-R interval variability (RRV) abnormalities (factors in the hypothesized pathway to MOD and CVD Co- morbidity); and 3) extent to which the associations between elevated maternal-fetal cytokines and MOD and CVD risks are mediated by offspring's HPA, cytokine, and RRV abnormalities. We will use data derived from the New England cohort of the National Collaborative Perinatal Project and the California Child Health & Development Study, which have rich and comparable pregnancy & developmental data and archived sera from pregnancy. 350 same-sex sibling sets, gestational ages 38-42 weeks and now ages 39-47, will be sampled who are discordant for either fetal growth restriction (n=175 sets) or pre-eclampsia (n=175 sets), two exposures significantly associated with substantial variation in elevated maternal-fetal cytokines. We will evaluate these subjects in adulthood to relate adult HPA, RRV and cytokine abnormalities as mediators of the association between fetal cytokine abnormalities with adult MOD and CVD risks. Findings will have important implications for understanding the etiology of MOD and CVD co-morbidity and the potential development of hormonal or immunoregulatory interventions to prevent them during fetal development.

描述（由申请人提供）：成年后，主要抑郁症（MOD）与心血管疾病风险（CVD）之间存在很高的合并症，这是全球残疾和死亡率的两个主要原因。该应用将检验假设这些疾病有共同的产前前因，这将有助于理解其成年后的病因和同时发生。研究表明，细胞因子（TNF-A，IL-1P，IL-6，CRP），HPA激素异常与MOD和CVD风险之间存在显着关联。我们关于胎儿先例的假设是基于证据表明，一些与调节情感有关的主要大脑区域也参与了控制心脏R-R间隔（RRV）和血压的炎症反应，HPA轴和ANS。我们建议HPA激素和细胞因子TNF-A，IL-1P，IL-6，这些共享的大脑区域表达是MOD和CVD风险之间的关键联系，始于产前发育。我们的主要目的是测试：1）升高的母体胎盘细胞因子水平与MOD＆CVD风险之间的关联； 2）较高的母体雌性细胞因子与成人后代的HPA轴，细胞因子TNF-A，IL-1（3，3，IL-6，CRP）与心脏的R-R间隔可变性（RRV）异常（RRV）异常（在MOD和CVD CO-MERATENT的途径中的途径）和3级范围的途径；细胞因子，MOD和CVD风险是由后代的HPA，细胞因子和RRV异常介导的。我们将使用来自国家合作围产期项目的新英格兰队列和加利福尼亚儿童健康与发展研究的数据，这些研究具有丰富且可比的妊娠和发育数据以及怀孕期间存档的血清。将对350个同性兄弟姐妹组，38-42周的妊娠年龄和现在的39-47岁，他们将被取样，他们对胎儿生长限制（n = 175套）或前偏头痛（n = 175套）不一致（n = 175套）（n = 175套），两种暴露量显着相关，两次与较高的载有含量的含量相关。我们将在成年期评估这些受试者，以将成人HPA，RRV和细胞因子异常联系起来，这是胎儿细胞因子异常与成人MOD和CVD风险之间关联的介体。发现将对理解Mod和CVD合并症的病因以及激素或免疫调节性干预的潜在发展具有重要意义，以防止它们在胎儿发育过程中。