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

• 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
• 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

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.

该指导研究职业奖（K23）申请的目标是为研究从母亲到婴儿的精神病风险代际传递的生物，遗传和行为机制提供培训和创新模型。该培训将提供（1）临床和生物学研究方法的高级教育，以及（2）在评估和解释神经生物学和遗传数据方面的广泛的指导研究经验。培训内容将包括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生理实验室的扩展实验室经验。将开发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。将对200名母亲（100名PTSD阳性和100名创伤暴露PTSD阴性）及其7个月大的婴儿进行研究。将对婴儿进行血清素转运蛋白启动子基因上的“风险”等位基因多态性的基因分型，当前文献已有力地确定该多态性与痛苦调节能力的独特变异有关。将在几个低和高挑战的相互作用（自由游戏，教学任务，和静止的脸范式）与行为和神经生物学应激反应（皮质醇，心率变异性）的测量研究母婴二对。我们假设：（1）母亲PTSD将预测婴儿神经生物学应激调节不太理想，这种联系将由母亲行为介导;（2）婴儿遗传“风险”的存在将预测婴儿神经生物学应激调节不太理想，这种关系将由母亲行为调节。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，这些数据是作为独立资助的临床科学家随后取得成功所需的，研究代际风险传递的复杂，交易和纵向途径。