Neurodevelopmental Correlates of Psychopathology Following Infant Maltreatment

在美国，早期生活压力，如虐待儿童，是一个主要的健康问题，因为它对身体和心理都有不利的影响。虐待不仅会对受害者造成身体伤害，还会使受害者更容易患上许多精神疾病，包括焦虑症、抑郁症、行为障碍、社交无能和认知功能障碍。这些结果在本质上被认为是神经发育的结果，是在发育早期对虐待经历的反应中反复激活应激系统的结果。前瞻性、纵向研究是解决这一假设的必要条件。因此，本研究的目标是在非人类灵长类动物模型中纵向研究与儿童虐待相关的精神病理学的神经发育基础。本研究将聚焦于虐待猴子模型中前额叶-杏仁核回路的发育改变。涉及这些回路的精神病理，如恐惧、焦虑、行为抑制，以及一般的情绪调节障碍，在虐待受害者中可以观察到。横断面研究的证据确实表明，这些区域的变化与虐待有关；然而，尚不清楚这些回路的改变是否导致了相关行为和精神病理的改变。了解这些神经回路的改变是如何导致精神病理的，不仅会导致治疗的发展，还有助于确定治疗的关键发育时期，并可能预防不良后果。目的1将使用尖端的纵向神经成像技术（结构MRI和弥散张量成像- DTI-）研究前额叶-杏仁核回路的发展，目的2将使用敏感的实验室任务研究情绪行为的发展。在这两个目标中收集的数据将在非人类灵长类动物的婴儿虐待模型中检查大脑和行为之间的关系。在申请研究期间，我将有机会从两位在这些领域具有丰富经验的研究人员那里学习最先进的纵向神经成像，灵长类动物大脑和行为的发展以及转化神经科学。在博士的指导下。通过我们与Martin Styner博士（UNC- Chapel Hill）的密切合作，我将有一个独特的机会来发展我的强大潜力和科学热情，在发育行为神经科学领域从事富有成效和独立的研究事业，重点是体内神经成像。在耶基斯进行的转化发展工作类型使用社会饲养的非人灵长类动物，以及博士的强大合作。桑切斯和巴切瓦利耶与儿童发展研究人员的合作绝对是独一无二的，这使它成为我启动长期职业目标的理想场所。

Early life stress, such as child maltreatment, is a major health concern in the United States due to both adverse physical and psychological consequences. Maltreatment not only results in physical harm to the victim, but puts the victim at higher risk for developing many psychopathologies including anxiety disorders, depression, conduct disorders, social incompetence and cognitive dysfunction. These outcomes are thought to be neurodevelopmental in nature, a consequence of repeated stress system activation in response to maltreatment experiences early in development. Prospective, longitudinal studies are necessary to address this hypothesis. Thus the goal of this proposal is to longitudinally examine the neurodevelopmental basis of psychopathologies associated with child maltreatment in a nonhuman primate model. This proposal will focus on the developmental alterations of prefrontal-amygdala circuits in a monkey model of maltreatment. Psychopathologies involving these circuits, such as fear, anxiety, behavioral inhibition and, in general, emotional regulation disorders are observed in victims of maltreatment. Evidence from cross-sectional studies does show alterations in these regions associated with maltreatment; however it is unknown whether altered development of these circuits underlies the alterations in associated behaviors and psychopathologies. Understanding how altered development of these circuits results in psychopathology would not only lead to treatment development, but also contribute to the identification of critical developmental periods for treatment, and possibly prevention, of adverse outcomes. Aim 1 will examine the development of prefrontal-amygdala circuits using cutting-edge longitudinal neuroimaging techniques (structural MRI and diffusion tensor imaging - DTI-) and Aim 2 will investigate development of emotional behavior using a sensitive laboratory task. The data collected in these two aims will be examined for relationships between brain and behavior throughout early development in a nonhuman primate model of infant maltreatment. During the proposed research I will have the opportunity to learn state-of-the-art longitudinal neuroimaging, development of the primate brain and behavior and translational neuroscience from two researchers with strong experience in these domains. With the guidance of Drs. Sanchez and Bachevalier at the Yerkes National Primate Research Center (Emory Univ), as well as through our close collaboration with Dr. Martin Styner (UNC- Chapel Hill), I will have a unique opportunity to develop my strong potential and scientific passion into a productive and independent research career in developmental behavioral neuroscience with a focus on in vivo neuroimaging. The type of translational developmental work being conducted at Yerkes using socially housed nonhuman primates, and the strong collaborations of Drs. Sanchez and Bachevalier with child development researchers is absolutely unique, making this the ideal arena for me to jumpstart my long-term career goals.