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Title page for ETD etd-08222016-130417


Type of Document Dissertation
Author Money, Kelli Marie
URN etd-08222016-130417
Title Inflammation and accumulating risk for developing psychiatric disorders
Degree PhD
Department Neuroscience
Advisory Committee
Advisor Name Title
Doug McMahon, PhD Committee Chair
Brad Grueter, PhD Committee Member
Bruce Carter, PhD Committee Member
Gregg Stanwood, PhD Committee Member
Kevin Ess, MD, PhD Committee Member
Keywords
  • gestational diabetes
  • depression
  • inflammation
  • maternal infection
Date of Defense 2016-08-16
Availability unrestricted
Abstract
The immune system and brain are intricately intertwined in both development and adult function. Unfortunately, this relationship can lead to dysfunction when balance in either system is disturbed. Inflammation does not have to be chronic nor excessive to predispose to psychiatric disorders but depends greatly on the genetic and other environmental factors it is combined with. In most cases, clinical data implicate increased inflammation and altered immune function in individuals with psychiatric disorders like MDD, autism, and schizophrenia. In our lab, we seek to uncover the role of inflammation in both psychiatric disorder pathogenesis and ongoing disease processes, especially in models of combined genetic and/or environmental risk factors. More specifically, we hypothesize that inflammation-associated psychiatric disorder risk factors interact, creating novel phenotypes not explainable by addition of either factor alone. In this document, we apply this central hypothesis to both gene x environment interactions (MDD genetic background in human dermal fibroblasts and exogenous cytokine exposure) as well as environment x environment interactions (combined gestational exposure to diabetes and maternal immune activation). We found that in both of these types of interactions a novel transcriptional phenotype was uncovered, supporting that inflammation-associated risk factors that increase risk for psychiatric disorder do interact. Although the study of individual risk factors is crucial, we believe that studying the interaction of well-characterized, commonly co-occurring genetic and/or environmental risk factors brings the field closer to clinically relevant phenotypes. Further understanding of inflammation in these domains focuses attention on when and what inflammatory factors should be addressed to prevent and/or lessen severity of psychiatric disorders.
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