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

• 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
• 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

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）：确定疾病风险的个体差异如何出现是生物医学研究的主要目标。早期生活经历可能对终生疾病和其他不良后果的风险至关重要。确定早期经历改变整个生命周期健康轨迹的范围、程度和机制对于公共卫生意义非常重大。幼儿期是预防和干预的一个极其有价值的窗口，旨在避免人类痛苦和经济负担方面的成本，否则这些成本有可能在个人的一生中不断升级。童年时期的逆境是导致一生中持续存在的一系列负面健康结果的潜在危险因素。揭示这些早期经历如何增加风险和健康轨迹变化对于制定更好的预防、干预和治疗策略以改善人类健康非常重要。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了解早期不良经历对复杂生物行为、认知和神经生物学功能的影响提供了重要而独特的机会，在相对较长的寿命中，其成熟过程与人类相似。然而，针对猴子早期生命事件的终生后果的纵向研究却异常稀少。由于缺乏关于早期不良经历如何改变中年和晚年时期的发育和健康的信息，这对使用这种动物模型进行研究提出了挑战。这里提出的研究的总体目标是解决这些关键的知识差距。这些研究将采用纵向研究方法来确定不同的早期养育经历（托儿所与母亲养育）对现有成年恒河猴中年期（14-19岁；大致范围在40-60岁）行为和大脑的特定方面的影响。本研究的具体目的是： 1) 确定早期差别饲养对恒河猴行为特定方面的长期影响； 2）利用磁共振成像（MRI）确定早期差别养育对大脑形态和大脑组成的整体和特定方面的长期影响； 3) 评估这些保育猴和母猴的认知、学习和记忆测试表现与大脑结构之间的关系； 4) 评估中年成熟期大脑和行为中与年龄相关的变化。这些研究将利用现有的独特动物种群，产生有关中年成熟期认知、学习、记忆和大脑的新的、立即有用的数据。总之，拟议的研究将解决有关童年逆境的长期动物模型的未解答的问题，并将产生有关早期经历对整个生命周期健康的影响的新信息。