Early experience and emotional development in free-ranging primates

自由放养灵长类动物的早期经历和情感发展

• 批准号: 8284329
• 负责人: DARIO MAESTRIPIERI
• 金额: $ 33.29万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8284329
• 关键词: 3 year old; Affect; Affective; Alleles; Anxiety; Arousal; Attenuated; Behavioral; Behavioral inhibition; Biological; Birth; Caregivers; Cercopithecus tantalus; Child; Cognitive; Corticotropin; Data; Development; Emotional; Environmental Risk Factor; Exhibits; Exploratory Behavior; Exposure to; Fostering; Genes; Genetic; Genetic Polymorphism; Genotype; Grooming; Human; Hydrocortisone; Individual; Infant; Island; Life; Macaca mulatta; Measures; Mediating; Metyrapone; Modeling; Mothers; Neurobiology; Neurosecretory Systems; Outcome; Oxytocin; Parenting behavior; Peptides; Phenotype; Physiology; Plasma; Population; Primates; Psychopathology; Psychosocial Stress; Puerto Rico; Research; Resistance; Risk; Saimiri; Social Network; Social support; Stress; System; Testing; Variant; base; behavior influence; behavior measurement; cohort; dexamethasone suppression test; early experience; emotion regulation; experience; hypothalamic-pituitary-adrenal axis; maternal separation; monoamine; neurobiological mechanism; novel; offspring; parental influence; physical abuse; programs; psychosocial; research study; resilience; response; sample collection; serotonin transporter; social; social separation; social skills; stress related disorder; stress resilience; stressor; therapy design

DESCRIPTION (provided by applicant): Using a primate model, we build on our previous research to test the novel hypothesis that exposure to moderate levels of maternal rejection early in life "inoculates" the developing infant by permanently altering cognitive appraisal of, and neuroendocrine sensitivity to, subsequent stressors (i.e., stress resilience). In contrast, we posit that exposure to too little or too much rejection-related stress leads to stress vulnerability later in life. We also test the hypotheses that these maternal influences on the development of stress resilience and vulnerability 1) result from long-term alterations in the activity of the serotonergic system, the HPA axis, and other stress-sensitive neurobiological systems, and 2) are modulated by risk or protective factors such as polymorphisms in the serotonin transporter (SERT) gene and amount of social support. This 5-year project will be conducted with the free-ranging population of rhesus macaques on Cayo Santiago, PR. Two cohorts of 45 infants (n=90) will be followed longitudinally from birth through 3 years of age. Infants will be classified on the basis of the amount of maternal rejection they receive (low, moderate, high) in the first 2-3 months of life. All infants will be SERT genotyped and homozygous or heterozygous individuals for the long and the short allele (l/l, l/s, and s/s) will be identified. Data on dominance rank, maternal protectiveness, and social support (social network size; grooming received; aid during agonistic interactions) will be quantified. Stress vulnerability and resilience will be operationalized with behavioral and neuroendocrine measures. Behavioral measures will include: a) independence from the mother; b) social competence during interactions with conspecifics; and c) behavioral inhibition and anxiety in response to "challenge" tests involving exposure to novel objects, unfamiliar humans, and risky social situations. Detailed characterization of HPA axis physiology and other stress-related neurobiological systems will be obtained through: a) frequent fecal sample collection to determine basal and stress-induced cortisol levels; b) assessment of plasma concentrations of ACTH and cortisol in response to psychosocial stress (social separations) and pharmacological challenges (CRF challenge, dexamethasone suppression test, metyrapone test, ACTH challenge); and c) assessment of stress-induced CSF concentrations of CRF, oxytocin, and monoamine metabolites. By conducting experimental research with free-ranging primates we maximize the ecological validity of our findings. This research will provide original information on the neuroendocrine mechanisms through which exposure to variable parenting can affect the development of stress vulnerability and resilience in children, and how genetic and environmental factors may influence these development outcomes. This research will also enhance our understanding of normative interindividual variation in the development of emotion regulation and stress-related disorders. Ultimately, this research may provide important information on the efficacy and potential limitations of parenting interventions designed to foster resilience in children based on controlled exposure to, and mastery of, psychosocial adversity.

描述（由申请人提供）：使用灵长类动物模型，我们在之前的研究基础上测试了一个新假设，即生命早期暴露于中等水平的母体排斥会通过永久改变对后续压力源的认知评估和神经内分泌敏感性（即压力恢复能力）来“接种”发育中的婴儿。相比之下，我们认为接触太少或太多与拒绝相关的压力会导致晚年的压力脆弱性。我们还测试了这样的假设：这些母亲对压力恢复能力和脆弱性发展的影响1）是由于血清素能系统、HPA轴和其他压力敏感神经生物系统的活动的长期变化造成的，2）受到风险或保护因素的调节，例如血清素转运蛋白（SERT）基因的多态性和社会支持的量。这个为期 5 年的项目将在波多黎各圣地亚哥岛的自由放养恒河猴种群中进行。两组 45 名婴儿 (n=90) 将从出生到 3 岁进行纵向随访。将根据婴儿在出生后 2-3 个月内受到的母体排斥程度（低、中、高）对婴儿进行分类。所有婴儿都将进行 SERT 基因分型，并鉴定长等位基因和短等位基因（l/l、l/s 和 s/s）的纯合或杂合个体。有关支配地位、母亲保护和社会支持（社交网络规模、接受的梳理、竞争互动期间的援助）的数据将被量化。压力脆弱性和恢复力将通过行为和神经内分泌措施来实施。行为措施包括： a) 独立于母亲； b) 与同种人互动时的社交能力； c) 应对“挑战”测试的行为抑制和焦虑，这些“挑战”测试涉及接触新物体、不熟悉的人类和危险的社交情境。 HPA 轴生理学和其他与压力相关的神经生物学系统的详细特征将通过以下方式获得： a) 频繁采集粪便样本以确定基础和压力诱导的皮质醇水平； b) 评估响应社会心理压力（社会分离）和药理学挑战（CRF 挑战、地塞米松抑制试验、美替拉酮试验、ACTH 挑战）的 ACTH 和皮质醇血浆浓度； c) 评估应激诱导的 CSF 中 CRF、催产素和单胺代谢物的浓度。通过对自由放养的灵长类动物进行实验研究，我们最大限度地提高了研究结果的生态有效性。这项研究将提供有关神经内分泌机制的原始信息，通过这种机制，暴露于可变的养育方式可以影响儿童的压力脆弱性和复原力的发展，以及遗传和环境因素如何影响这些发展结果。这项研究还将增强我们对情绪调节和压力相关疾病发展中规范个体差异的理解。最终，这项研究可能会提供有关育儿干预措施的有效性和潜在局限性的重要信息，这些干预措施旨在通过控制接触和掌握社会心理逆境来培养儿童的适应力。