Perinatal Experience and Children's Mental Health

围产期经历和儿童心理健康

• 批准号: 6768796
• 负责人: Delia M Vazquez
• 金额: $ 17.21万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6768796
• 关键词: animal data; child behavior; child mental disorders; child psychology; cognition; developmental neurobiology; developmental psychology; early experience; emotions; hypothalamic pituitary adrenal axis; limbic system; literature survey; neurobiology; perinatal; species difference

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.

描述（由申请人提供）：情感疾病的许多方面，包括抑郁症，都涉及边缘皮质情绪回路的紊乱。在许多此类情况下，可以观察到边缘-下丘脑-垂体-肾上腺 (LHPA) 轴持续或不适当的激活。这一一级网络应用（产前和围产期经历以及儿童心理健康）的综合目标是加强以下概念和经验之间的联系：1）啮齿动物、绵羊和非人类灵长类动物关于不良早期经历和 LHPA 轴发育的研究，和2）对胎儿、围产期和/或新生儿早期早期逆境经历的情感和认知后遗症的人类研究。我们的持久目标是开发合作研究项目，旨在研究不良胎儿和早期新生儿经历对 LHPA 发育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，特别是与易受伤害有关精神疾病。我们具体假设，在子宫内和/或围产期可能引发的 LHPA 轴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，导致容易患上精神疾病。通过整合受邀研究人员提供的多样化专业知识，我们的目标是开发动物范例，以适当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开发测量人类对胎儿和/或新生儿逆境的反应模式的方法所需的背景。已经确定了四个概念性主题，构成了该网络的具体目标。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）跨物种的发育窗口和等效性，3）子宫内和/或围产期不良经历和长期后遗症：关键要素的作用LHPA 轴，以及 4) 在遗传脆弱性和精神疾病恢复力方面的个体差异。我们利用这些会议组织了 9 场计划网络会议中的前 5 场会议，最后 3 场会议专门讨论和完善研究和拨款提案计划。十二名网络成员，涵盖啮齿动物、绵羊、猴子以及人类胎儿和婴儿群体的分子、行为和流行病学层面的专业知识，以及两名顾问将加入该小组，讨论特定的主题和会议。网络成员包括：Charles R. Neal 和 Delia M. Vaizquez（联合 PI）、K. Sunny Anand、Ronald G. Barr、Alice S. Carter、Christopher Coe、Michael K. Georgieff、Vivette Glover、Kate Keenan、Michael S克莱默、彼得·纳撒尼尔兹和帕蒂克·瓦德瓦。顾问是 Megan Gunnar 和 Seymour Levine。拟议的网络最终将促进假设驱动的研究计划，并制定新的策略，有效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精神疾病联系起来。 。