Perinatal Experience and Children's Mental Health

描述(申请人提供)：情感性疾病的许多方面，包括抑郁症，涉及边缘-皮质情绪回路的障碍。边缘-下丘脑-垂体-肾上腺(LHPA)轴持续或不适当的激活在许多情况下都可以观察到。这项名为“产前和围产期体验与儿童心理健康”的一级网络应用的综合目标是加强概念和经验上的联系：1)啮齿动物、绵羊和非人类灵长类动物对不良早期体验和LHPA轴发育的研究，以及2)人类对胎儿、围产期和/或早期新生儿时期早期逆境经历的情感和认知后遗症的研究。我们的长期目标是开发合作研究计划，旨在研究不利的胎儿和早期新生儿经历对LHPA发育的神经生物学的长期影响，这些影响与婴儿、儿童和青少年的认知和情感功能有关，特别是与精神疾病的易感性有关。我们特别假设，在子宫和或围产期可以启动的LHPA轴的关键要素的改变可能是由各种不利的环境条件引起的。如果有适当的遗传基础，这种不良的早期生活经历可能会创造一个神经生物学基础，导致易患精神疾病。通过整合由受邀研究人员组成的小组提供的各种专业知识，我们的目标是开发动物范例，适当地模拟胎儿和新生儿逆境对人类LHPA发育的潜在影响的分子和神经生物学过程。这样的讨论将不可避免地提供必要的背景，以开发一种方法来衡量人类对胎儿和/或新生儿逆境的反应模式。已经确定了构成该网络的具体目标的四个概念性主题。这些主题是：1)产前和围产期动物模型及其对人类状况的有效性，2)发育窗口和跨物种的等效性，3)宫内和/或围产期不良经历和长期后遗症：LHPA轴关键要素的作用，以及4)遗传脆弱性和精神疾病韧性方面的个体差异。我们用它们来组织计划中的9个网络会议中的前5个，最后3个会议专门讨论和完善研究和拨款提案计划。已经召集了12名网络成员，他们的专业知识从啮齿动物、绵羊、猴子以及人类胎儿和婴儿种群的分子水平到行为和流行病学水平，以及将加入该小组的两名顾问，他们将参加特定主题和会议。网络成员是：Charles R.Neal和Delia M.Vaizquez(Co-Pi)、K.Sunny Anand、Ronald G.Barr、Alice S.Carter、Christopher Coe、Michael K.Georgief、Vivette Glover、Kate Keenan、Michael S.Kramer、Peter Nathanielsz和Pathik Wadhwa。顾问是梅根·冈纳和西摩·莱文。拟议的网络最终将促进假说驱动的研究倡议，并开发新的战略，有效地测试胎儿和新生儿的不良经历对LHPA发育的影响，将临床产科和新生儿学、流行病学、发育神经解剖学和神经科学与儿童和青少年的精神疾病联系起来。

DESCRIPTION (provided by applicant): Many aspects of affective illness, including depression, involve a disturbance in the limbic-cortical emotional circuitry. A persistent or inappropriate activation of the limbic-hypothalamic-pituitary-adrenal (LHPA) axis is observed in many of these conditions. The comprehensive goal of this Level I Network application, Prenatal and Perinatal Experience and Children's Mental Health, is to strengthen the conceptual and empirical linkages between: 1) rodent, sheep and non-human primate research on adverse early experiences and development of the LHPA axis, and 2) human research on the emotional and cognitive sequelae of early adversity experiences during the fetal, perinatal and/or early neonatal period. Our enduring goal is to develop collaborative research programs designed to study the long-term effects of adverse fetal and early neonatal experience on the neurobiology of LHPA development in relation to cognitive and emotional function in infants, children and adolescents, particularly in relation to vulnerability to mental illness. We specifically hypothesize that alterations in key elements of the LHPA axis that can be initiated in utero and or in the perinatal period may be brought about by a variety of adverse environmental conditions. Given an appropriate genetic substrate, such adverse early life experiences may create a neurobiological foundation that leads to vulnerability to mental illness. By integrating the diverse expertise provided by the assembled group of invited researchers, our objective is to develop animal paradigms that appropriately model the molecular and neurobiological processes underlying effects of fetal and neonatal adversity on LHPA development in the human. Such discussions will inevitably provide the background necessary to develop a means to measure human response patterns to fetal and/or neonatal adversity. Four conceptual topics have been identified that form the specific aims this network. These topics are: 1) Prenatal and perinatal animal models and their validity to the human condition, 2) Developmental windows and equivalency across species, 3) In utero and/or perinatal adverse experiences and long term sequelae: the role of key elements of the LHPA axis, and 4) Individual differences with respect to genetic vulnerability, and resilience, to mental illness. We have used these to organize the first 5 of the 9 planned network meetings, with the last 3 meetings devoted to discussing and refining research and grant proposal plans. Twelve network members, spanning expertise from molecular to behavioral and epidemiological levels in rodent, sheep, monkey, and human fetal and infant populations have been assembled, along with two consultants who will join the group for specified topics and meetings. Network members are: Charles R. Neal and Delia M. Vaizquez (Co-PI's), K. Sunny Anand, Ronald G. Barr, Alice S. Carter, Christopher Coe, Michael K. Georgieff, Vivette Glover, Kate Keenan, Michael S. Kramer, Peter Nathanielsz and Pathik Wadhwa. The consultants are Megan Gunnar and Seymour Levine. The proposed network will ultimately foster hypothesis driven research initiatives, and develop new strategies that will effectively test the impact of adverse fetal and neonatal experience on LHPA development, bridging clinical obstetrics and neonatology, epidemiology, developmental neuroanatomy and neurosciences with mental illness in children and adolescents.