Neurodevelopmental Correlates of Psychopathology Following Infant Maltreatment

早期生活压力，如虐待儿童，是美国的一个主要健康问题，因为它会对身体和心理产生不良影响。虐待不仅对受害者造成身体伤害，而且使受害者更有可能患上许多精神疾病，包括焦虑症、抑郁症、品行障碍、社交能力低下和认知功能障碍。这些结果被认为是神经发育的本质，是在发育早期对虐待经历做出反应的反复应激系统激活的结果。前瞻性的纵向研究是必要的，以解决这一假设。因此，本建议的目标是纵向研究与儿童虐待在非人类灵长类动物模型的精神病理学的神经发育基础。 这项建议将集中在前额叶杏仁核电路的虐待猴子模型的发展变化。在虐待受害者中观察到涉及这些回路的精神病理学，如恐惧、焦虑、行为抑制和一般的情绪调节障碍。横断面研究的证据确实表明这些区域的改变与虐待有关;然而，这些回路的改变是否是相关行为和精神病理学改变的基础还不清楚。了解这些回路的改变如何导致精神病理学的发展，不仅会导致治疗的发展，而且有助于确定治疗的关键发展时期，并可能预防不良后果。目标1将使用尖端的纵向神经成像技术（结构MRI和扩散张量成像- DTI-）检查前额叶杏仁核回路的发展，目标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。 在拟议的研究期间，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，灵长类动物大脑的发育以及行为和转化神经科学。在Yerkes国家灵长类动物研究中心（埃默里大学）的Sanchez博士和Bachevalier博士的指导下，以及通过我们与Martin Styner博士的密切合作，我将有一个独特的机会，将我强大的潜力和科学热情发展成为一个富有成效的独立研究事业，专注于体内神经成像的发展行为神经科学。在耶基斯进行的转化发展工作使用社会圈养的非人类灵长类动物，以及桑切斯和巴切瓦利埃博士与儿童发展研究人员的密切合作绝对是独一无二的，这使得这成为我启动长期职业目标的理想竞技场。

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.