Long-term Cognitive and Neuroanatomical Consequences of Childhood Stress

童年压力的长期认知和神经解剖学后果

基本信息

批准号：
8473280
负责人：
ALLYSON J BENNETT
金额：
$ 35.29万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-01 至 2015-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8473280
关键词：
Address Adolescence Adult Adverse event Affect Animal Experimentation Animal Model Animals Behavior Behavioral Biomedical Research Brain Cerebrum Childhood Cognition Cognitive Complex Corpus Callosum Data Development Disease Economic Burden Elderly Environment Event Goals Gray unit of radiation dose Health Hippocampus (Brain)Human Individual Individual Differences Intervention Knowledge Learning Life Life Experience Light Long-Term Effects Longevity Macaca mulatta Magnetic Resonance Imaging Measures Memory Modeling Monkeys Mothers Motor Neurobiology Nurseries Outcome Pathway interactions Performance Physiological Population Prefrontal Cortex Prevention strategy Preventive Intervention Process Public Health Relative (related person)Research Risk Risk Factors Severities Short-Term Memory Stress Testing Variant Work adverse outcome age related biobehavior brain behavior brain morphology caudate nucleus cognitive function cost disorder risk early childhood early experience executive function experience improved lifetime risk middle age nonhuman primate novel public health relevance putamen treatment strategy white matter

项目摘要

DESCRIPTION (provided by applicant): Identifying how individual differences in risk for disease emerge is a major target for biomedical research. Early life experiences may be pivotal in lifetime risk of disease and other adverse outcomes. The public health significance of identifying the scope, extent, and mechanisms by which early experiences alter health trajectories across the lifespan is extraordinarily high. Early childhood represents a critically valuable window for prevention and intervention aimed at averting costs, both in terms of human suffering and economic burden, that otherwise have the potential to escalate across an individual's life. Adversity in childhood is a potent risk factor for a range of negative health outcomes persisting throughout the lifespan. Uncovering how these early experiences generate increased risk and variation in health trajectories is important for the development of better prevention, intervention, and treatment strategies to improve human health. Animal models and animal research are essential to achieving these goals. Nonhuman primate studies offer significant and unique opportunities for understanding the consequences of early adverse experiences on complex biobehavioral, cognitive, and neurobiological functions across a relatively long lifespan that parallels humans in terms of maturational processes. Longitudinal research that addresses the lifelong consequences of early life events in monkeys is exceptionally sparse, however. The dearth of information about how early adverse experiences alter development and health across the middle- and later-life periods poses a challenge to use of this animal model for research. The broad goal of the research proposed here is to address these critical gaps in knowledge. The studies will use a longitudinal research approach to identify the consequences of different early rearing experiences (nursery- versus mother-reared) on specific aspects of behavior and brain in middle- age (14-19 years; approximate range within 40-60 human years) in an existing population of adult rhesus monkeys. The specific aims of this research are: 1) To determine the long-term effects of early differential rearing on specific aspects of behavior in rhesus macaques; 2) To determine the long-term effects of early differential rearing on both global and specific aspects of brain morphology and cerebral composition using magnetic resonance imaging (MRI); 3) To assess the relationship between performance on cognitive, learning and memory tests and structural aspects of the brain in these nursery- and mother-reared monkeys; and, 4) To evaluate age-related changes in both brain and behavior across the middle-age maturational period. These studies will leverage a unique existing population of animals to produce new and immediately useful data on cognition, learning, memory, and brain in the middle-age maturational period. Together, the proposed studies will address unanswered questions about a long-standing animal model of childhood adversity and will produce novel information about the consequences of early experience on health across the lifespan.

描述（由申请人提供）：确定疾病风险中的个体差异如何是生物医学研究的主要目标。早期生活经历可能是疾病和其他不良后果的终生风险。识别早期经验改变寿命的健康轨迹的范围，程度和机制的公共卫生意义非常高。幼儿时期代表着一个非常有价值的预防和干预措施，旨在避免成本，无论是在人类的痛苦和经济负担方面，否则就有可能在个人的生活中升级。童年时期的逆境是整个生命周期中持续存在的一系列负面健康结果的有效风险因素。揭示这些早期经历如何产生健康轨迹的风险和差异对于发展更好的预防，干预和治疗策略以改善人类健康至关重要。动物模型和动物研究对于实现这些目标至关重要。非人类灵长类动物研究为理解早期不良经历对复杂的生物行为，认知和神经生物学功能的后果提供了重要的机会，这在相对较长的寿命中，与人类在成熟过程中相关。但是，解决猴子早期生活事件的终生后果的纵向研究异常稀疏。关于早期不良经历如何改变了中期和后期时期的发展和健康的信息，这对使用该动物模型进行研究构成了挑战。这里提出的研究的广泛目标是解决知识中的这些关键差距。这些研究将使用纵向研究方法来确定在现有的成年恒河猴人群中，在中年（14-19岁；在40-60人类年内）在中年（14-19岁；在40-60人类年内近似范围）的特定方面的不同早期饲养经历（托儿所与母亲饲养）的后果。这项研究的具体目的是：1）确定早期差异饲养对恒河猕猴行为特定方面的长期影响； 2）使用磁共振成像（MRI）确定早期差异饲养对脑形态和脑组成的全球和特定方面的长期影响； 3）评估这些托儿所和母亲饲养的猴子在认知，学习和记忆测试和大脑结构方面的表现之间的关系；和4）评估与年龄相关的大脑和行为的变化。这些研究将利用独特的现有动物种群在中年成熟时期生成有关认知，学习，记忆和大脑的新的有用数据。拟议的研究一起将解决有关长期存在的儿童逆境动物模型的未解决问题，并将产生有关整个生命周期早期经验的后果的新颖信息。