Understanding Neurodevelopment in Macaques with Different Rearing Experiences

描述(申请人提供)：虐待儿童是一个主要的公共卫生问题。除了身体受伤或死亡的风险外，早期虐待还与社交能力、情绪调节和认知方面的损害有关，以及在以后的生活中发展成焦虑、情绪和成瘾障碍的风险增加。虽然人们认为这些脆弱性反映了对神经发育的影响，但出于实际和伦理方面的考虑，无法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轻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、非人类的灵长类动物模型来解决这个问题，这种模型是人类童年虐待的。有趣的是，虐待不仅是人类的问题，在非人类灵长类动物中也有报道，虐待的比率和类型与人类相似。这一恒河猴模型提供了一种方法，利用神经成像技术来表征婴儿虐待对神经发育的长期影响。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比较受虐和非受虐动物的纵向分析的合理性，并需要关于早期发育的标准数据来确定早期不良经历导致神经结构和神经回路的扰动发生在哪里。这一建议的总体假设基于这样一种观点，即虐待婴儿通过对压力反应的持续敏感化，扰乱正常的神经发育，包括控制社会情绪行为和压力生理的神经系统。这个项目有两个目标，都是应用尖端的活体神经成像技术和方法来研究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将定义虐待婴儿对神经发育的长期后果，描述早期接触虐待婴儿的猴子和从青春期过渡到成年的未虐待对照组猴子之间的大脑差异。目标2将定义恒河猴神经发育的标准变化，从出生后早期到18个月大。将评估神经发育变化与社会情绪发育和身体发育的关系。在密切相关的亲缘关系中了解婴儿虐待的神经发育后果将为确定人类童年虐待对神经发育的影响提供框架，为理解其在儿童和青少年的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利后果。

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.