Early experience and emotional development in free-ranging primates

描述（由申请人提供）：使用灵长类动物模型，我们建立在我们先前的研究基础上来测试新的假设，即在生命早期暴露于中等水平的母体排斥通过永久改变对随后的应激源（即，压力恢复力）。相比之下，我们认为，接触太少或太多与拒绝有关的压力会导致以后生活中的压力脆弱性。我们还检验了以下假设：1）这些母亲对压力恢复力和脆弱性发展的影响是由α-羟色胺能系统、HPA轴和其他压力敏感神经生物学系统的长期活动改变引起的; 2）受到风险或保护因素的调节，如5-羟色胺转运体（SERT）基因的多态性和社会支持的数量。这个为期5年的项目将进行自由放养的人口恒河猴的Cayo圣地亚哥，PR。两个队列的45名婴儿（n=90）将纵向从出生到3岁。婴儿将根据他们在出生后的前2-3个月内接受的母亲排斥程度（低、中、高）进行分类。将对所有婴儿进行SERT基因分型，并鉴定长和短等位基因（l/l、l/s和s/s）的纯合或杂合个体。将对优势等级、母性保护和社会支持（社交网络大小;接受梳理;在竞争性相互作用期间的援助）的数据进行量化。压力脆弱性和复原力将与行为和神经内分泌措施一起运作。行为措施将包括：a）独立于母亲; B）在与同种个体互动时的社会能力;以及c）对“挑战”测试的反应中的行为抑制和焦虑，所述“挑战”测试包括暴露于新物体、不熟悉的人和危险的社会情境。HPA轴生理学和其他应激相关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，以确定基础和应激诱导的皮质醇水平; B）评估响应于心理社会应激的ACTH和皮质醇的血浆浓度（社会分离）和药理学挑战（CRF激发、地塞米松抑制试验、甲吡酮试验、ACTH激发）;和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我们发现的生态有效性。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弹性的发展，以及遗传和环境因素如何影响这些发展结果。这项研究也将加强我们对情绪调节和压力相关疾病发展中的规范性个体间差异的理解。最终，这项研究可能会提供重要的信息的有效性和潜在的局限性，父母的干预措施，旨在促进儿童的基础上控制暴露，掌握，心理社会逆境的韧性。 公共卫生相关性：建议的项目将提供有关神经内分泌机制的原始信息，通过这些机制，暴露于可变的父母可以影响儿童的压力脆弱性和复原力的发展。这也将提高我们的理解，父母的压力反应的发展的影响是如何调制的遗传和环境因素。本研究的发现对于理解儿童情绪调节发展中的个体间差异以及压力相关障碍具有重要意义。

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. PUBLIC HEALTH RELEVANCE: The proposed project 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. It will also enhance our understanding of how parental influences on the development of stress reactivity are modulated by genetic and environmental factors. Findings of this research have important implications for understanding normative interindividual variation in the development of emotion regulation as well as stress-related disorders in children.