Investigating the Associations Between Trauma Exposure and Conditioned Inhibition of Fear in Development
Date of Award
Spring 2023
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Neuroscience
First Advisor
Gee, Dylan
Abstract
Exposure to trauma is pervasive, impacting up to two-thirds of children and adolescents and a quarter of all adults in our society (Alisic et al., 2014; Copeland et al., 2018; Green et al., 2010; McLaughlin et al., 2013). Responses to traumatic experiences can help individuals navigate a society and world that has harmed them, and, in many cases, can lead to significant distress and interfere with daily life. Accordingly, the mental health sequalae following trauma exposure are profound, with up to 15% of youth (Alisic et al., 2014; Copeland et al., 2007; McLaughlin et al., 2012, 2013) and 6-8% of adults (Kessler et al., 2005; Koenen et al., 2017) experiencing posttraumatic stress disorder (PTSD) and anxiety disorders. In addition, nearly 45% of all childhood and 30% of all adult mental health conditions are associated with childhood trauma (Green et al., 2010), highlighting a need to understand factors that link trauma exposure and negative mental health in order to facilitate early intervention. Although current evidence-based treatments for PTSD and anxiety such as exposure-based cognitive behavioral therapy (CBT) can be beneficial for many individuals (Cusack et al., 2016; Morina et al., 2016), a significant portion of youth and adults do not experience sufficient improvements (Creswell et al., 2020; Gillies et al., 2012; Ginsburg et al., 2018; Hudson, Keers, et al., 2015; James et al., 2015b; Loerinc et al., 2015; Walkup et al., 2008). Importantly, exposure-based CBT relies on principles of fear extinction, a process that is diminished during adolescence (Pattwell et al., 2012). Thus, optimizing approaches to fear reduction using a developmentally- and trauma-informed approach is of critical importance for youth living with anxiety and PTSD following traumatic life experiences (Gee & Casey, 2015). Safety signal learning–a class of conditioned inhibition–is one such mechanism of fear reduction in which a safety cue is repeatedly trained (or conditioned) to signal the non-occurrence of an aversive outcome and in turn inhibit conditioned fear responses in the presence of threat (Christianson et al., 2012; Rescorla, 1969). Indeed, evidence across species has demonstrated that safety signal learning is successful in attenuating a conditioned fear responses (Christianson et al., 2012; Odriozola & Gee, 2021). Furthermore, safety signal learning has been shown to recruit an anterior hippocampal-dorsal anterior cingulate cortex pathway (Meyer et al., 2019a), which may undergo a different developmental trajectory compared to the frontoamygdala connections that support fear extinction (Pattwell et al., 2016). Additionally, safety signal learning has also been shown to be associated with PTSD in adults, suggesting a potential role as a mediator between trauma and psychopathology in youth. Thus, delineating age- and trauma-related differences in safety signal learning and the associated neural processes may shed light not only on a potential novel approach to fear reduction for youth with PTSD and anxiety following trauma exposure, but also on a potential process linking trauma exposure and mental health outcomes such as PTSD and anxiety. In this dissertation, I present three empirical studies that examine the associations between trauma exposure and conditioned inhibition via safety signal learning by leveraging physiological, behavioral, and neuroimaging (i.e., functional magnetic resonance imaging; fMRI) data that were collected while youth and adults completed a developmentally-adapted conditioned inhibition paradigm in the scanner. In the introduction to this dissertation (Chapter 1), I briefly review the extant literature on fear learning and extinction and associations with trauma exposure, discuss theories on mechanisms of fear reduction, and provide an overview of safety signal learning in the context of trauma and PTSD. In Study 1 (Chapter 2), I elucidate the associations between trauma exposure and fear reduction via safety signal learning and the associated neural mechanisms in adults without psychopathology. In Study 2 (Chapter 3), I delineate age-related associations between trauma exposure and behavioral and neural correlates of safety signal learning in children and adolescents. Finally, in Study 3 (Chapter 4), I examine safety signal learning as a potential mechanism linking trauma exposure and psychopathology, specifically PTSD and anxiety. I conclude with a general discussion (Chapter 5) in which I propose key future directions for this research and discuss the clinical implications of the present work.
Recommended Citation
Kribakaran, Sahana, "Investigating the Associations Between Trauma Exposure and Conditioned Inhibition of Fear in Development" (2023). Yale Graduate School of Arts and Sciences Dissertations. 1014.
https://elischolar.library.yale.edu/gsas_dissertations/1014
