Early Adversity and Human Microbiome-Hippocampal Development: Anxiety Associations

项目摘要/摘要 我的职业目标是领导一个多学科的研究团队，研究 早期逆境和焦虑之间的路径。该实验室将实施跨物种模型，使用 跨多个生物和心理系统进行向前和向后翻译以揭示 可延展性的干预点，然后可以针对年龄适当地影响焦虑的变化 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种 扎实的临床/发展心理学、啮齿动物行为和分子方面的技能基础 神经科学。我的职业发展计划在这一技能的基础上进行扩展，以提供必要的进一步培训 压力/逆境、发育、记忆、功能核磁共振、微生物生态分析和精神病理学。通过 从事这段保障训练的时间，我将进入我的独立研究阶段，为领导做好准备 第一个专门成立的研究小组是为了研究微生物组-脑相互作用的发展 在逆境之后。研究项目：早期的逆境经历是导致焦虑的重要因素 精神错乱。然而，逆境-焦虑联系背后的发展机制仍然难以捉摸。 大量证据表明，焦虑的出现与两个系统有关，这两个系统受 早期逆境：胃肠道微生物组和海马体记忆系统。虽然研究表明 独立发现逆境、焦虑、微生物和海马体发育之间的关联 微生物组和海马区记忆在焦虑产生中的共享和交互作用 症状从未被检查过。拟议项目的目标是产生纵向数据 集合集成了典型和逆境暴露的微生物、海马体和记忆信息 开发样本，并使用这些数据来发现最终导致焦虑的预测路径。具体而言，在 根据我的初步数据，我将检验逆境对焦虑的影响是中介的假设 通过改变微生物组和海马体记忆系统的顺序路径。合而为一 综合研究I将确定早期逆境对微生物组组成的影响 发育(目标1)，在检查微生物组和基于海马体的联系之前 典型发育人类的记忆成熟(目标2)。最后，在R00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区的途径发生 记忆发育改变(目标3)。阐明独立和互动的贡献 微生物组和海马体对焦虑的记忆系统对于识别治疗靶点是必不可少的 可应用于遭遇逆境的个体，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.