Early experience and emotional development in free-ranging primates

描述（由申请人提供）：利用灵长类动物模型，我们在之前的研究基础上验证了一个新的假设，即在生命早期暴露于中等水平的母亲排斥，通过永久改变对后续压力源（即压力恢复力）的认知评估和神经内分泌敏感性，“接种”了发育中的婴儿。相反，我们假设，暴露在太少或太多的与拒绝相关的压力下，会导致在以后的生活中出现压力脆弱性。我们还测试了以下假设：1)这些母亲对压力恢复和脆弱性发展的影响源于血清素能系统、HPA轴和其他压力敏感神经生物系统活性的长期改变；2)受血清素转运体（SERT）基因多态性和社会支持量等风险或保护因素调节。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的恒河猴种群中进行。两组45只婴儿（n=90）将从出生到3岁进行纵向跟踪。婴儿将根据他们在出生后的头2-3个月接受的母亲排斥程度（低、中、高）进行分类。所有婴儿都将进行SERT基因分型，并确定长等位基因（l/l， l/s和s/s）的纯合或杂合个体。将对优势等级、母亲保护和社会支持（社会网络规模、获得的梳理、竞争相互作用中的援助）的数据进行量化。应激脆弱性和恢复力将通过行为和神经内分泌措施进行操作。行为措施包括：a)脱离母亲的独立性；B)与同种个体互动时的社会能力；c)行为抑制和焦虑对“挑战”测试的反应，包括暴露于新物体，不熟悉的人，以及危险的社会环境。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：a)频繁收集粪便样本以确定基础和应激诱导的皮质醇水平；b)评估血浆ACTH和皮质醇浓度对社会心理应激（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）的反应；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。本研究将提供神经内分泌机制的原始信息，通过这种机制，暴露于不同的养育方式可以影响儿童的压力脆弱性和恢复力的发展，以及遗传和环境因素如何影响这些发展结果。本研究也将增强我们对情绪调节和压力相关障碍发展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，说明父母干预的有效性和潜在的局限性，这些干预旨在通过控制暴露和掌握心理逆境来培养儿童的弹性。

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. 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.