Perinatal Stress and Gene Influences: Pathways to Infant Vulnerability

描述（由申请人提供）：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，由一个调查小组（由多部门、多机构和社区从业人员组成）领导，具有良好的生产力和职业发展记录。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易感性的作用。”

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