Investigating the Associations Between Safety Cue Learning and Trauma Exposure in Development

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Exposure to trauma throughout the lifespan, and in particular during childhood and adolescence, is prevalent, with more than two-thirds of all children in the United States having experienced at least one traumatic event by age 16. It is well-established that exposure to trauma can lead to psychopathology (e.g., anxiety disorders, posttraumatic stress disorder) in many individuals. Thus, it is imperative to not only optimize and devise novel interventions for individuals suffering from the effects of trauma, but also to identify the mechanisms by which trauma exposures confer risk for psychopathology to aid efforts in risk identification and early intervention. The primary treatment approach for both adults and youth with anxiety and other trauma-related disorders is exposure-based cognitive behavioral therapy (CBT). Exposure-based CBT draws on principles of extinction learning in which individuals repeatedly encounter cues relating to the traumatic event in the absence of the threat or aversive outcome, thereby extinguishing their fear response over time. The behavior of extinction learning and its supporting neural circuitry have been delineated in the last several decades in adult rodent models and human samples. Critically, growing cross-species evidence from developmental studies suggests that extinction learning undergoes key changes across development, and in particular during the adolescent period during which extinction learning is diminished. Notably, these behavioral changes coincide with nonlinear changes in frontolimbic circuitry that supports fear learning and extinction. Delineating mechanisms of fear reduction that leverage these non-linear changes is therefore of critical importance. We propose to investigate safety cue learning (SCL) as a potential novel and developmentally-sensitive approach to optimize fear reduction in youth with trauma exposure, anxiety disorders, or both. Furthermore, given that one of the mechanisms thought to link trauma exposure and psychopathology involves threat and safety learning, SCL may serve an important mechanistic role. In Aim 1, I will use skin conductance response as an index of physiological reactivity while participants complete a SCL task to examine the association between trauma exposure and SCL among children, adolescents, and young adults (8-30 years of age) with and without anxiety. In Aim 2, I will examine the associations between trauma exposure and the neural mechanisms of SCL, namely hippocampal-frontoamygdala circuitry, in the same sample using functional magnetic resonance imaging. For Aims 1 and 2, I will also compare SCL to extinction learning and examine whether there are any age-related changes in SCL and related frontolimbic circuitry that are associated with trauma exposure. Finally, in Aim 3, I will test whether SCL and related frontolimbic circuitry mediate the association between trauma exposure and anxiety in children, adolescents, and young adults. In summary, the aims of this study will investigate SCL as a potential mechanism linking trauma exposure and anxiety and examine SCL as a novel approach to optimize fear reduction, thus carrying high clinical relevance and future translational potential.