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: 7931872
• 负责人: ZACHARY N STOWE
• 金额: $ 190.49万
• 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/7931872
• 关键词: Perinatal; Stress; Gene; Influences; Pathways

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.

本中心申请响应PAR-04-151：行为科学转化研究中心（TRCBS）。该中心位于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，由一个调查团队（由多部门，多机构和社区从业人员组成）领导，具有生产力和职业发展承诺的良好记录。高度互动的翻译设计将“阐明围产期事件、易感基因和胎儿暴露对后代日后精神病理学脆弱性的作用。" 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取决于母体、胎盘和胎儿间室的代谢能力、敏感性和亲和力。该中心将前瞻性地跟踪有围产期抑郁风险的妇女、亲生父亲和后代，直至怀孕和产后第一年-收集DMA三重奏、母体压力的生物指标和母体症状。围产期评估将包括子宫血流、胎儿活动和产科结局。将在几个产后时间点收集婴儿的行为/情感、神经生物学和心理生理学指标。胎儿抗抑郁药暴露的影响将纳入统计模型，以确定这种暴露对后代脆弱性的潜在调节作用。 通过描述母体行为，并收集介导母体应激和抗抑郁药暴露的神经生物学机制的侵入性评估，在大鼠中对临床人群进行建模。这些大鼠模型将为围产期应激和抗抑郁药暴露的行为、生理和遗传后果提供独特的见解。 拟议中的中心将测试我们的广泛假设，即怀孕期间的母亲精神疾病构成了一个早期的环境暴露，改变了后代的脆弱性，以后来的精神病理学在一个遗传脆弱的人口。这项工作将促进我们对基因和早期环境对后代发育轨迹的影响的理解。此外，该中心将潜在地确定增强胎儿易感性的妊娠窗口。量化孕妇抑郁/焦虑和抗抑郁药在怀孕期间使用的影响的数据对美国每年超过400，000名妇女的护理有直接的临床意义。