Perinatal Stress and Gene Influences: Pathways to Infant Vulnerability

描述(申请人提供)：本中心申请响应PAR-04-151：行为科学翻译研究中心(TRCBS)。该中心总部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，由一个调查小组(由多部门、多机构和社区从业者组成)领导，他们在生产力和对职业发展的承诺方面有着良好的记录。这项互动性很强的翻译设计将“阐明围产期事件、易感基因和胎儿暴露对后代日后精神疾病易感性的作用(S)。” 母亲的压力、抑郁和焦虑可能会改变宫内环境。这种初始发育环境的成分取决于母体、胎盘和胎儿的新陈代谢能力、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、怀孕和出生后第一年的子女-聚集DMA三人组、母亲压力的生物学指数和母亲的症状。围产期评估将包括子宫血流、胎儿活动和产科结局。将在婴儿出生后的几个时间点收集行为/情感、神经生物学和心理生理学的测量结果。胎儿接触抗抑郁剂的影响将被纳入统计模型，以确定这种接触对后代易感性的潜在缓和作用。 临床人群将通过描述母亲的行为特征，并收集对调节母亲应激和抗抑郁药物暴露的神经生物学机制的侵入性评估，在大鼠中进行建模。这些大鼠模型将为围产期应激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。 拟议中的中心将检验我们的广泛假设，即孕妇怀孕期间的精神疾病构成了早期环境暴露，改变了遗传脆弱人群中后代对后来精神病理的易感性。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，该中心还可能确定胎儿易感性增强的孕期窗口。量化怀孕期间母亲抑郁/焦虑和抗抑郁药物使用的影响的数据对美国每年40万名妇女的护理具有直接的临床意义。 整体中心

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