Early Adversity and Human Microbiome-Hippocampal Development: Anxiety Associations

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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.