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: 8472356
• 负责人: DARIO MAESTRIPIERI
• 金额: $ 31.6万
• 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/8472356
• 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，我们以先前的研究为基础，以测试新的假设，即在生命早期的早期孕产妇拒绝水平的暴露“接种”通过永久改变对神经内分泌的认知评估和神经内分泌敏感性，对后来的压力（即压力弹性）。相比之下，我们认为，暴露于太少或太多的与排斥相关的压力会导致生活以后的压力脆弱性。我们还测试了这些假设，即这些母体对压力弹性和脆弱性的影响1）由血清素能系统的活动，HPA轴以及其他对压力敏感的神经生物学系统的长期变化而导致的。这个为期5年的项目将与圣地亚哥Cayo Santiago的自由放养人群进行。从出生到3岁，将纵向跟踪两个45名婴儿（n = 90）的队列（n = 90）。婴儿将根据他们在生命的头2-3个月接受的母亲拒绝（低，中等，高）的量进行分类。将鉴定所有婴儿的基因分型，纯合子或杂合个体，而短等位基因（l/l，l/s和s/s）将被识别。关于主导地位，孕产妇保护性和社会支持（社交网络规模；收到的修饰；在激动互动期间的援助）的数据将被量化。压力脆弱性和弹性将通过行为和神经内分泌措施来实现。行为措施将包括：a）与母亲独立； b）与同种互动的互动期间的社会能力； c）响应“挑战”测试的行为抑制和焦虑，包括暴露于新颖的物体，陌生的人类和危险的社交情况。 HPA轴生理学和其他与压力相关的神经生物学系统的详细表征将通过以下方式获得： b）评估响应社会心理压力（社会分离）和药理学挑战（CRF挑战，地塞米松抑制测试，Metyrapone测试，ACTH挑战）的ACTH和皮质醇的血浆浓度； c）评估应力诱导的CSF浓度的CRF，催产素和单胺代谢物。通过使用自由放大灵长类动物进行实验研究，我们最大程度地提高了发现的生态有效性。这项研究将提供有关神经内分泌机制的原始信息，通过这些信息，可变育儿的暴露会影响儿童的压力脆弱性和韧性的发展，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与压力相关的疾病发展的规范性个体差异的理解。最终，这项研究可能会提供有关旨在基于受控的心理社会逆境受控和精通的育儿干预措施的效力和潜在限制的重要信息。