Infant Stress Response: Effects of Maternal PTSD and Infant Genes

描述（由申请人提供）：本指导研究职业奖（K23）申请的目标是为精神疾病风险从母亲到婴儿的代际传递的生物学、遗传和行为机制的研究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)在评估和解释神经生物学和遗传数据方面的广泛指导研究经验。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项目（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生理学实验室扩展的实验室经验。将建立模型来研究风险的代际传递，重点关注患有PTSD的母亲、婴儿的遗传风险因素及其对婴儿神经生物学应激调节的影响。200名母亲（100名创伤后应激障碍阳性和100名创伤暴露后应激障碍阴性）及其7个月大的婴儿将被研究。婴儿将根据5 -羟色胺转运启动子基因上的“风险”等位基因多态性进行基因分型，这在当前文献中已被明确地确定为与窘迫调节能力的独特差异有关。将在几个低挑战和高挑战的互动（自由游戏，教学任务和仍然面对范式）中研究母子二人组，并测量行为和神经生物学应激反应（皮质醇，心率变异性）。我们假设：(1)母亲创伤后应激障碍对婴儿神经生物学应激调节的影响较小，这种影响可能通过母亲行为来调节；(2)婴儿存在遗传“风险”会导致婴儿神经生物学应激调节不佳，而这种关系会受到母亲行为的调节。教学培训、指导研究经验和模型开发相结合，将为申请人提供知识、技能和高质量的初步数据，使其成为一名独立资助的临床科学家，研究代际风险传递的复杂、交易和纵向途径。

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.