Infant Stress Response: Effects of Maternal PTSD and Infant Genes

婴儿应激反应：母亲 PTSD 和婴儿基因的影响

基本信息

批准号：
7888148
负责人：
Maria Muzik
金额：
$ 17.93万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-22 至 2012-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7888148
关键词：
Address Adult Alleles Animal Experimentation Anxiety Arousal Autonomic nervous system Behavior Behavioral Mechanisms Biological Birth Child Clinical Clinical Research Complex Corticotropin-Releasing Hormone Receptors Critical Pathways Data Development Diagnosis Disease Distress Dopamine Education Educational process of instructing Environment Environmental Risk Factor Face Figs - dietary Foundations Funding Future Gene Expression Generations Genes Genetic Genetic Polymorphism Genetic Predisposition to Disease Genetic Risk Genotype Glucocorticoid Receptor Goals Human Hydrocortisone Infant Infant Behavior Infant Development Knowledge Laboratories Link Literature Maternal Behavior Mediating Mental disorders Mentored Patient-Oriented Research Career Development Award Mentors Michigan Modeling Mothers Neurobiology Neurosecretory Systems Outcome Pathway interactions Physiological Play Population Post-Traumatic Stress Disorders Postpartum Period Psychopathology Psychophysiology Recruitment Activity Regulation Relative (related person)Research Research Design Research Methodology Research Personnel Risk Role Sampling Scientist Serotonin Shapes Social Interaction Stress System Testing Training Trauma Universities Variant Work behavior measurement beta-2 Adrenergic Receptors biological adaptation to stress biological research biological systems career caregiving deviant dopamine D4 receptor emotional distress experience genetic risk factor heart rate variability high risk hypothalamic-pituitary-adrenal axis infant outcome innovation intergenerational model development offspring prenatal prenatal influence prenatal stress programs promoter receptor resilience response serotonin transporter skills success transmission process

项目摘要

DESCRIPTION (provided by applicant): The goal of this Mentored Research Career Award (K23) application is to provide training and innovative models for research on the biological, genetic and behavioral mechanisms underlying the intergenerational transmission of psychiatric risk from mother to infant. The training will provide (1) advanced education in clinical and biological research methodology, and (2) extensive, mentored research experience in assessment and interpretation of neurobiological and genetic data. The training components will include formal coursework in the University of Michigan Clinical Research Design and Statistical Analysis Program (CRDSA) under the Michigan CTSA, and extended laboratory experiences through the University of Michigan Genetics Laboratory and Trauma, Stress, and Anxiety Research Group's neurobiological and psycho-physiological laboratories. Models will be developed to study intergenerational transmission of risk, focusing on mothers with PTSD, infant's genetic risk factors, and their impact on infants' neurobiological stress regulation. Two-hundred mothers (100 PTSD-positive and 100 trauma-exposed PTSD-negative) and their 7-month old infants will be studied. Infants will be genotyped for the "risk" allele polymorphisms on the serotonin transporter promoter gene, which has been robustly identified in the current literature as related to unique variation in capacity for distress regulation. Mother-infant dyads will be studied in several low-and high challenge interactions (Free Play, Teaching Task, and Still Face Paradigm) with measurement of behavioral and neurobiological stress responses (cortisol, heart rate variability). We hypothesize that (1) maternal PTSD will predict less optimal infant neurobiological stress regulation, and this link will be mediated by maternal behavior; (2) presence of genetic "risk" in the infant will predict less optimal infant neurobiological stress regulation, and this relation will be moderated by maternal behavior. The combination of didactic training, mentored research experience and model development will provide the applicant with the knowledge, skills, and high quality preliminary data needed for the subsequent success as an independently funded clinical scientist, studying the complex, transactional, and longitudinal pathways of intergenerational risk transmission.

描述（由申请人提供）：本指导研究职业奖（K23）申请的目标是为研究精神风险从母亲到婴儿的代际传播的生物、遗传和行为机制提供培训和创新模型。培训将提供（1）临床和生物学研究方法方面的高级教育，以及（2）在神经生物学和遗传数据的评估和解释方面广泛的、受指导的研究经验。培训内容将包括密歇根大学 CTSA 下的密歇根大学临床研究设计和统计分析计划 (CRDSA) 的正式课程，以及通过密歇根大学遗传学实验室和创伤、压力和焦虑研究小组的神经生物学和心理学扩展实验室经验。 -生理实验室。将开发模型来研究风险的代际传播，重点关注患有创伤后应激障碍的母亲、婴儿的遗传风险因素及其对婴儿神经生物应激调节的影响。将对 200 名母亲（100 名 PTSD 阳性和 100 名遭受创伤的 PTSD 阴性）及其 7 个月大的婴儿进行研究。将对婴儿的血清素转运蛋白启动子基因上的“风险”等位基因多态性进行基因分型，该基因已在当前文献中被有力地鉴定为与应激调节能力的独特变异有关。母婴二人组将在几种低挑战和高挑战互动（自由游戏、教学任务和静止面孔范式）中进行研究，并测量行为和神经生物学压力反应（皮质醇、心率变异性）。我们假设（1）母亲的 PTSD 将预测不太理想的婴儿神经生物学应激调节，并且这种联系将由母亲行为介导； (2) 婴儿中存在遗传“风险”将预测婴儿神经生物学应激调节不太理想，并且这种关系将受到母亲行为的调节。教学培训、指导研究经验和模型开发的结合将为申请人提供知识、技能和高质量的初步数据，以便申请人随后成为一名独立资助的临床科学家，研究代际间复杂的、事务性的和纵向的路径。风险传递。