Perinatal Stress and Gene Influences: Pathways to Infant Vulnerability

围产期压力和基因影响：婴儿脆弱性的途径

• 批准号: 7486136
• 负责人: ZACHARY N STOWE
• 金额: $ 193.85万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7486136
• 关键词: Perinatal; Stress; Gene; Influences; Pathways

DESCRIPTION (provided by applicant): This Center application responds to PAR-04-151: Translational Research Centers in Behavioral Sciences (TRCBS). Based in the Department of Psychiatry and Behavioral Sciences of the Emory University School of Medicine, the center includes 3 cores and 4 projects led by an investigative team (consisting of multi- departmental, multi-institutional, and community practitioners) with a proven track record of productivity and commitment to career development. The highly interactive translational design will "elucidate the role(s) of perinatal events, susceptibility genes, and fetal exposures on the vulnerability of the offspring to later psychopathology." The intrauterine environment can be altered by maternal stress, depression, and anxiety. The constituents of this initial developmental milieu depend on the metabolic capacities, sensitivities, and affinities of the maternal, placental, and fetal compartments. The Center will prospectively follow women at risk for peri-partum depression, biological fathers, and offspring through pregnancy and the first postnatal year - gathering DMA trios, biological indices of maternal stress, and maternal symptoms. Perinatal assessments will include uterine blood flow, fetal activity, and obstetrical outcome. Behavioral/affective, neurobiological, and psychophysiological measures will be gathered on infants at several post-natal time points. The impact of fetal antidepressant exposure will be incorporated into statistical models to determine the potential moderating role of such exposure on the vulnerability of the offspring. The clinical population will be modeled in rats by characterizing maternal behavior, and gathering invasive assessments of neurobiological mechanisms mediating exposure to maternal stress and antidepressants. These rat models will provide unique insights into the behavioral, physiological, and genetic consequences of perinatal stress and antidepressant exposure. The proposed Center will test our broad hypothesis that maternal mental illness during pregnancy constitutes an early environmental exposure that alters vulnerability of offspring to later psychopathology in a genetically vulnerable population. The work will advance our understanding of the influence of genes and early environment on the developmental trajectory of offspring. In addition, the Center will potentially identify gestational windows of enhanced fetal susceptibility. Data that quantifies the impact of maternal depression/anxiety and antidepressant use during pregnancy has direct clinical implications for the care of >400,000 women each year in the United States. Overall Center

描述（由申请人提供）：该中心申请响应 PAR-04-151：行为科学转化研究中心 (TRCBS)。该中心设在埃默里大学医学院精神病学和行为科学系，包括 3 个核心和 4 个项目，由一个具有良好记录的调查团队（由多部门、多机构和社区从业者组成）领导。生产力和对职业发展的承诺。高度互动的转化设计将“阐明围产期事件、易感基因和胎儿暴露对后代易受精神病理学影响的作用。” 子宫内环境可能会因母亲的压力、抑郁和焦虑而改变。这种初始发育环境的组成部分取决于母体、胎盘和胎儿的代谢能力、敏感性和亲和力。该中心将前瞻性地跟踪有围产期抑郁症风险的女性、生父和后代在怀孕期间和产后第一年的情况——收集 DMA 三重奏、孕产妇压力的生物指数和孕产妇症状。围产期评估将包括子宫血流量、胎儿活动和产科结果。将在出生后的几个时间点收集婴儿的行为/情感、神经生物学和心理生理学测量结果。胎儿抗抑郁药物暴露的影响将被纳入统计模型中，以确定此类暴露对后代脆弱性的潜在调节作用。 通过表征母亲行为并收集介导母亲压力和抗抑郁药物暴露的神经生物学机制的侵入性评估，将在大鼠中建立临床人群模型。这些大鼠模型将为围产期压力和抗抑郁药物暴露的行为、生理和遗传后果提供独特的见解。 拟议的中心将测试我们的广泛假设，即母亲怀孕期间的精神疾病构成了早期环境暴露，从而改变了遗​​传脆弱人群中后代对后期精神病理学的脆弱性。这项工作将增进我们对基因和早期环境对后代发育轨迹影响的理解。此外，该中心还将有可能确定胎儿易感性增强的妊娠窗口。量化孕期母亲抑郁/焦虑和抗抑郁药物使用影响的数据对美国每年超过 400,000 名女性的护理具有直接的临床意义。 整体中心