Understanding Neurodevelopment in Macaques with Different Rearing Experiences

描述（由申请人提供）：虐待儿童是一个重大的公共卫生问题。除了身体伤害或死亡的风险外，早期虐待还与社交能力、情绪调节和认知能力受损有关，并与以后生活中出现焦虑、情绪和成瘾障碍的风险增加有关。虽然人们一直认为这些脆弱性反映了对神经发育的影响，但现实和伦理问题阻碍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。目前的建议解决这个问题，通过使用一个独特的，自然的，非人类灵长类动物模型的人类童年虐待。有趣的是，虐待不仅仅是人类的问题；据报道，在非人类灵长类动物中也有这种情况，虐待的发生率和类型与人类相似。这个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来证明对受虐待和未受虐待动物进行纵向分析的合理性，以及早期发育的规范性数据，以确定早期不良经历导致的神经结构和回路的扰动。这一提议的总体假设是基于这样一种观点，即婴儿虐待通过持续的应激反应敏化，破坏了正常的神经发育，包括控制社会情绪行为和应激生理的神经系统。本项目有两个目标，都是应用前沿的活体神经成像技术和方法，研究不同饲养经历动物的大脑结构、连通性和功能的组织。目的1将定义婴儿虐待对神经发育的长期影响，描述早期暴露于婴儿虐待的猴子和未受虐待的对照组从青春期过渡到成年期的大脑差异。目标2将定义恒河猴神经发育的规范变化，从出生后早期到18个月大。将评估神经发育变化与社会情感发展和身体生长的关系。理解一个密切相关的系统发育亲属的婴儿虐待的神经发育后果，将为定义人类儿童虐待的神经发育影响提供框架，为理解其在儿童和青少年社会情绪问题和病理生理学发展中的作用提供参考，并有助于设计治疗计划，寻求限制儿童虐待的不良后果。

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.