Neurodevelopmental Correlates of Psychopathology Following Infant Maltreatment

婴儿虐待后精神病理学的神经发育相关性

• 批准号: 8265008
• 负责人: BRITTANY ROLLINS HOWELL
• 金额: $ 3.09万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-10 至 2013-06-09
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8265008
• 关键词: Address; Adolescence; Adolescent; Affect; Amygdaloid structure; Animal Model; Anxiety; Anxiety Disorders; Behavior; Behavior Control; Behavior monitoring; Behavioral; Behavioral inhibition; Birth; Brain; Child Abuse and Neglect; Child Development; Collaborations; Cross-Sectional Studies; Data; Data Analyses; Data Collection; Development; Diffusion Magnetic Resonance Imaging; Disease; Emotional; Fright; Functional disorder; Goals; Health; Housing; Human; Image; Impaired cognition; Infant; Intervention; Investigation; Laboratories; Lead; Learning; Letters; Life; Life Stress; Link; Longitudinal Studies; Macaca; Macaca mulatta; Magnetic Resonance Imaging; Measures; Mediating; Mental Depression; Methods; Modeling; Monkeys; Mood Disorders; Nature; Neurobiology; Neurosciences; North Carolina; Outcome; Physiological; Population; Prefrontal Cortex; Prevalence; Prevention; Prevention strategy; Primates; Process; Psychopathology; Regulation; Reporting; Research; Research Personnel; Resources; Risk; Role; Social Interaction; Stress; Structure; Substance abuse problem; Symptoms; System; Techniques; Testing; Time; TimeLine; Training; United States; Weight; Work; adverse outcome; base; biological adaptation to stress; brain behavior; career; critical developmental period; early experience; experience; high risk; in vivo; longitudinal design; maltreatment; neurobiological mechanism; neurochemistry; neurodevelopment; neuroimaging; nonhuman primate; physical abuse; physical neglect; primate development; prospective; psychologic; relating to nervous system; response; social; therapy development; translational neuroscience; treatment strategy; white matter

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.

早年的生活压力，如虐待儿童，在美国是一个主要的健康问题，因为它会产生不利的身体和心理后果。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、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，是发育早期虐待经历反复激活应激系统的结果。为了解决这一假设，有必要进行前瞻性的纵向研究。因此，这项建议的目标是在非人类灵长类动物模型中纵向检查与虐待儿童相关的精神病理学的神经发育基础。 这项建议将集中在虐待猴子模型中前额叶-杏仁核回路的发育变化。涉及这些回路的精神病理，如恐惧、焦虑、行为抑制，以及一般情况下的情绪调节障碍，都会在虐待的受害者身上观察到。来自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变化是否是相关行为和精神病理变化的基础。了解这些回路的改变发展如何导致精神病理学，不仅将导致治疗的发展，而且还有助于确定治疗的关键发育期，并可能预防不良后果。Aim 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-)来研究前额-杏仁核回路的发育，Aim 2将使用敏感的实验室任务来研究情绪行为的发展。在这两个目标中收集的数据将在婴儿虐待的非人类灵长类动物模型中检查大脑和早期发育过程中行为之间的关系。 在拟议的研究期间，我将有机会从两名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、灵长类大脑的发展以及行为和翻译神经科学。在耶克斯国家灵长类动物研究中心(埃默里大学)的桑切斯博士和巴切瓦利埃博士的指导下，以及通过我们与马丁·斯泰纳博士(北卡罗来纳大学教堂山分校)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开发成一份富有成效的独立研究生涯，在发育行为神经科学领域，重点是体内神经成像。耶克斯使用社会安置的非人类灵长类动物进行的翻译开发工作，以及桑切斯博士和巴赫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，这使这里成为我启动长期职业目标的理想舞台。