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，我们建立在我们之前的研究基础上，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性地改变对后续应激源(即应激适应能力)的认知评估和神经内分泌敏感性，来“接种”发育中的婴儿。相反，我们假设，暴露在与拒绝相关的压力太少或太多会导致日后生活中的压力脆弱性。我们还检验了以下假设：1)5-羟色胺能系统、HPA轴和其他对应激敏感的神经生物学系统的活动长期变化，以及2)风险或保护性因素，如5-羟色胺转运体(SERT)基因和社会支持的数量的多态，这些母亲对应激韧性和脆弱性的发展产生的影响。这个为期5年的项目将在美国加州圣地亚哥的自由放养猕猴种群中进行。两个队列的45名婴儿(n=90)将从出生到3岁进行纵向跟踪。婴儿将根据他们在生命的头2-3个月收到的母亲排斥的数量(低、中、高)进行分类。所有婴儿均为SERT纯合子或杂合子个体，长短等位基因(L/L、L/S、S/S)将被识别。关于优势等级、母亲保护和社会支持(社会网络规模；接受的修饰；竞争互动期间的援助)的数据将被量化。应激脆弱性和恢复力将通过行为和神经内分泌措施来实施。行为测量将包括：a)独立于母亲；b)在与同种人互动时的社交能力；以及c)对涉及接触新对象、陌生人类和危险社交情景的“挑战”测试的行为抑制和焦虑。将通过以下途径获得HPA轴生理学和其他应激相关神经生物学系统的详细特征：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)评估应对心理社会应激(社会分离)和药物挑战(CRF挑战、地塞米松抑制试验、美泰龙试验、ACTH挑战)时血浆ACTH和皮质醇的浓度；以及c)评估应激诱导的脑脊液中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，不同的父母教养方式可以影响儿童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。这项研究还将加深我们对情绪调节和应激相关障碍发展过程中标准化个体间差异的理解。最终，这项研究可能会提供关于父母干预的有效性和潜在局限性的重要信息，这些干预旨在基于对心理社会逆境的控制暴露和掌握来培养儿童的韧性。

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.