Early Adversity and Cortico-Amygdala Activation During Fear Conditioning Among Adolescents

• In Event: 2-067 - Childhood Adversity and Fear Learning Mechanisms

Integrative Statement

Individuals with histories of early life adversity are at increased risk for anxiety disorders in adulthood (Scott, Smith, & Ellis, 2010), but the mechanisms underlying this association are not well understood. Existing research suggests that early life adversity sensitizes cortico-amygdala neurocircuitry that supports the detection of and response to threatening stimuli (Nusslock & Miller, 2016). Neural indices of fear responding to threat and non-threat stimuli can be measured via Pavlovian differential conditioning. Previous research has found evidence for aberrant fear conditioning among youth with histories of early adversity (McLaughlin et al., 2016), but studies to date have primarily focused on behavioral and physiological measures. The aim of the current study was to examine the relation between early life adversity and neural activation in key regions of the cortico-amygdala circuit during fear acquisition and extinction in a sample of 18- and 19-year-olds. It was hypothesized that history of early life adversities would predict neural activation in the amygdala and subgenual anterior cingulate cortex (sgACC) during fear acquisition and in ventromedial prefrontal cortex (vmPFC) during fear extinction.

Participants (N = 264) completed the Childhood Trauma Interview (Fink et al., 1995), which assesses instances of emotional, physical and sexual abuse, separations from and loss of caregivers, physical neglect, and witnessing violence between birth and age 18 years. Interviewers rated each instance on a scale from 1 (mild) to 6 (very extreme), resulting in counts of the number of minor (severity ≤ 2), major (severity ≥3) and total adversities. Participants also completed a differential Pavlovian conditioning paradigm while undergoing fMRI. Following standard preprocessing procedures, region of interest analyses compared activation to the conditional stimulus paired with electric shock (CS+) to the CS not paired with shock (CS-) during fear acquisition and fear extinction.

Linear regression was used to examine the prediction of neural activation for the CS+ versus CS- contrast in the three regions of interest from the number of minor, major and total adversities. The number of major adversities significantly predicted right amygdala (β =. 037, t(262) = 2.34, p = .02), sgACC (β = .245, t(262) = 4.10, p < .001), and vmPFC (β = .154, t(262) = 2.53, p = .012) activation during fear acquisition. Further, the total number of adversities significantly predicted sgACC activation during both fear acquisition (β = .207, t(262) = 3.43, p = .001) and fear extinction (β = .123, t(261) = 2.01, p = .046). Participants with numbers of major and total adversities above the median demonstrated less differentiation between the CS+ and CS- with regard to neural responding in the regions of interest during fear acquisition than participants with number of adversities below the median. During fear extinction, above-median participants demonstrated greater sgACC activation to the CS+ than below-median individuals. Although preliminary, the results suggest that adolescents with histories of adversity differ in their neural responding to safe and danger cues during fear conditioning, which may confer risk for anxiety in adulthood.

Authors

• Meghan Vinograd, University of California, Los Angeles
  Presenting Author

• Katherine S. Young, University of California, Los Angeles
  Non-Presenting Author

• Michael Sun, University of California, Los Angeles
  Non-Presenting Author

• Lindsay K. Staples-Bradley, University of California, Los Angeles
  Non-Presenting Author

• Katherine S. F. Damme, Northwestern University
  Non-Presenting Author

• Nicholas J. Kelley, Northwestern University
  Non-Presenting Author

• Iris K. Y. Chat, Northwestern University
  Non-Presenting Author

• Susan Y. Bookheimer, University of California, Los Angeles
  Non-Presenting Author

• Richard E. Zinbarg, Northwestern University
  Non-Presenting Author

• Robin Nusslock, Northwestern University
  Non-Presenting Author

• Michelle G. Craske, University of California, Los Angeles
  Non-Presenting Author