Early Adversity and Human Microbiome- Hippocampal Development: Anxiety Associations

项目总结/摘要 我的职业目标是领导一个多学科的研究团队，调查发展中国家的 早期逆境和焦虑之间的联系该实验室将实施一个跨物种模型，使用 在多个生物和心理系统之间进行向前和向后的翻译， 可延展的干预点，然后可以针对年龄适当的目标，以影响焦虑的变化 症状为了有效地领导这个未来的研究团队，我需要在以下领域进行强化培训： 微生物学、神经科学和发展心理学。到目前为止，我的训练为我提供了一个 在临床/发展心理学，啮齿动物行为学和分子生物学方面的技能的坚实基础 神经科学我的职业发展计划扩展了这一技能，以提供以下方面的必要进一步培训： 压力/逆境，发展，记忆，功能磁共振成像，微生物生态学分析，和精神病理学。通过 在这段有保障的训练时间里，我将为进入我的独立研究阶段做好充分的准备， 第一个专门研究微生物组与大脑相互作用的研究小组 在逆境之后。研究项目：早期的逆境经历是焦虑的重要因素 紊乱然而，发展机制的基础上的逆境焦虑联系仍然难以捉摸。 大量的证据表明，焦虑的出现涉及两个系统， 早期逆境：胃肠道微生物组和海马记忆系统。虽然研究 独立发现逆境，焦虑，微生物和海马发育之间的联系， 微生物组和海马记忆对焦虑出现的共享和交互作用 症状从未被检查过。拟议项目的目标是产生纵向数据 集合整合了典型和逆境暴露的微生物，海马和记忆信息 开发样本，并使用这些数据来揭示导致焦虑的预测途径。具体到 根据我的初步数据，我将检验这一假设，即逆境对焦虑的影响是介导的 通过改变微生物组和海马记忆系统的连续途径。在一个 综合研究I将确定早期逆境对微生物组组成的影响， 发展（目标1），然后再检查微生物组和基于细菌的 在典型发育中的人类中的记忆成熟（目标2）。最后，在R 00阶段，我将确定 逆境对焦虑的影响是否通过微生物改变和海马神经元的途径发生 记忆发育改变（目标3）。阐述联合国人权事务高级专员办事处 微生物组和海马记忆系统对焦虑的作用对于确定治疗靶点至关重要， 可应用于处于逆境中的个体，有益于终身心理健康。

PROJECT SUMMARY/ABSTRACT My career goal is to lead a multidisciplinary research team that investigates the developmental pathways between early adversity and anxiety. The lab will implement a cross-species model, using forwards and backwards translation across multiple biological and psychological systems to uncover malleable points of intervention, which can then be age-appropriately targeted to affect change in anxiety symptoms. To effectively lead this future research team, I require intensive training in the fields of microbiology, neuroscience, and developmental psychology. My training to date has provided me with a strong foundation of skills in clinical/developmental psychology, rodent behavior, and molecular neuroscience. My career development plan expands on this skill set to provide essential further training in stress/adversity, development, memory, fMRI, analysis of microbial ecology, and psychopathology. By engaging in this protected training time, I will enter my independent stage of research well prepared to lead the first research team purposefully established to study the development of microbiome-brain interactions following adversity. Research Project: Early experiences of adversity are strong contributors to anxiety disorders. However, the developmental mechanisms underlying the adversity-anxiety link remain elusive. Extensive evidence now implicates two systems in the emergence of anxiety, and which are affected by early adversity: the gastrointestinal microbiome and the hippocampal memory system. While studies have independently found associations between adversity, anxiety, microbial and hippocampal development, the shared and interactive effects of the microbiome and hippocampal memory on the emergence of anxiety symptoms have never been examined. The goal of the proposed project is to produce a longitudinal data set integrating microbial, hippocampal, and memory information across typical and adversity-exposed developing samples and to use this data to uncover predictive pathways that end in anxiety. Specifically, in line with my preliminary data, I will test the hypothesis that adversity effects on anxiety are mediated through a sequential pathway of alterations to the microbiome, and hippocampal memory systems. In one integrated study I will determine the effect of early adversity on microbiome composition across development (Aim 1), before examining the association between the microbiome and hippocampal-based memory maturation in typically developing humans (Aim 2). Finally, in the R00-phase I will determine whether effects of adversity on anxiety occur through the pathway of microbial alterations and hippocampal memory development alterations (Aim 3). Elucidating the independent and interactive contributions of the microbiome and hippocampal memory system to anxiety is essential for identifying treatment targets which can be applied to adversity exposed individuals, benefiting lifespan mental health.