Understanding Neurodevelopment in Macaques with Different Rearing Experiences

描述（由申请人提供）：虐待儿童是一个主要的公共卫生问题。除了身体伤害或死亡的风险外，早期虐待还与社会能力、情绪调节和认知能力受损有关，并增加了日后患焦虑、情绪和成瘾性疾病的风险。虽然人们认为这些脆弱性反映了对神经发育的影响，但实际和伦理问题阻止了在人类早期发育期间研究这些关联。然而，这些数据将有助于干预和减少与这些早期不良经历相关的心理健康负担。目前的建议通过使用一种独特的、自然主义的、非人类灵长类动物的人类童年虐待模型来解决这个问题。有趣的是，虐待不仅仅是人类的问题，在非人类灵长类动物中也有报道，虐待的发生率和类型与人类相似。这种恒河猴模型提供了一种方法来表征婴儿虐待对神经发育的长期影响，使用神经成像技术。然而，为了实现这一重要目标，需要使用体内神经成像的初步数据，以证明纵向分析比较虐待和非虐待动物，和规范性数据的早期发展，以确定在神经结构和电路的扰动发生的早期不良经验的结果。这一建议的总体假设是基于这样的论点，即婴儿虐待，通过持续敏感的压力反应，破坏正常的神经发育，包括神经系统的控制社会情绪行为和压力生理。该项目有两个目的，它们都应用尖端的体内神经成像技术和方法来研究具有不同饲养经验的动物的大脑结构，连接和功能的组织。目标1将定义婴儿虐待对神经发育的长期后果，表征早期暴露于婴儿虐待和非虐待对照的猴子从青春期向成年期过渡时的大脑差异。目的2将定义恒河猴从出生后早期到18个月龄的神经发育的正常变化。将评估神经发育变化与社会情感发育和身体发育的关系。意义了解神经发育的后果，婴儿虐待在一个密切相关的亲缘关系将提供一个框架，定义人类儿童期虐待的神经发育影响，了解其作用的发展中的社会情感问题和儿童和青少年的病理生理学的参考，并帮助设计治疗计划，寻求限制儿童期虐待的不良后果。

DESCRIPTION (provided by applicant): Child maltreatment is a major public health problem. In addition to the risk of physical injury or death, early maltreatment is associated with impairments in social competence, emotional regulation and cognition, as well as to an increased risk for the development of anxiety, mood, and addiction disorders later in life. While it has been assumed that these vulnerabilities reflect impacts on neurodevelopment, practical and ethical concerns prevent studying these associations during early human development. Yet, such data would aid attempts to intervene and reduce the mental health burden associated with these early adverse experiences. The present proposal addresses this problem by using a unique, naturalistic, nonhuman primate model of human childhood maltreatment. Interestingly, maltreatment is not just a human problem; it has been reported in nonhuman primates as well, with rates and types of maltreatment similar to those seen in human populations. This rhesus monkey model provides a means to characterize the long-term impact of infant maltreatment on neurodevelopment using neuroimaging technology. However, in order to accomplish this important goal, preliminary data using in vivo neuroimaging are needed to justify longitudinal analyses comparing abused and non-abused animals, and normative data on early development to determine where perturbations in neural structure and circuits occur as a consequence of early adverse experience. The overall hypothesis of this proposal is based on the argument that infant maltreatment, via a sustained sensitization of the stress response, disrupts normal neurodevelopment, including neural systems underlying the control of socioemotional behavior and stress physiology. There are two aims in this project, both of them applying cutting edge in vivo neuroimaging technology and approaches to study the organization of brain structure, connectivity and function in animals with different rearing experiences. Aim 1 will define the long-term consequences of infant maltreatment on neurodevelopment, characterizing brain differences between monkeys with early exposure to infant abuse and non-abused controls as they transition from adolescence to adulthood. Aim 2 will define normative changes in neurodevelopment in rhesus monkeys, from the early postnatal period until 18 months of age. Neurodevelopmental changes will be assessed for relationship to socioemotional development and physical growth. Significance Understanding the neurodevelopmental consequences of infant maltreatment in a closely related phylogenetic relative will provide the framework for defining the neurodevelopmental impact of human childhood maltreatment, a reference for understanding its role in the development of socioemotional problems and pathophysiology in children and adolescents, and aid the design of treatment plans seeking to limit the adverse consequences of childhood maltreatment.