Youth Exposed to Maltreatment Show Age-related Alterations in Hippocampal-Frontoamygdala Function During Extinction Recall

• In Event: Growing up in a Social Context: Brain and Emotional Development From Infancy to Early Adolescence

Abstract

The early environment has a profound impact on brain and behavioral development, particularly in the affective domain. Delineating the neurodevelopmental mechanisms linking early adversity with affective behavior and mental health is critical for the early identification of risk and optimizing interventions to promote resilience. Youth exposed to maltreatment show alterations in fear conditioning and related hippocampal-frontoamygdala circuitry, yet much remains unknown about how maltreatment affects extinction and extinction recall, which are important for discriminating threat from safety in the environment. Youth ages 8-17 years old (N=161) with or without exposure to maltreatment completed fear acquisition and extinction while skin conductance response was monitored. Within one week, participants completed extinction recall and re-extinction during functional magnetic resonance imaging (fMRI) scanning. Given hypotheses about maltreatment and frontolimbic development, we tested for group differences in age-related patterns of activation in the amygdala, hippocampus, and subgenual anterior cingulate cortex (sgACC) during extinction recall and re-extinction. Maltreatment-exposed youth showed altered age-related activation in the amygdala (F(1,125)=5.40, p=.022) and hippocampus (F(1,125)=4.58, p=.034) during extinction recall. Whereas non-exposed youth showed stable activation, maltreatment-exposed youth showed age-related increases in amygdala and hippocampus activation to the safety cue (relative to the threat cue). A maltreatment x age x sex interaction (F(1,125)=4.86, p=.029) revealed that maltreatment-exposed females (but not males) had altered age-related sgACC activation to the threat cue (relative to the safety cue) during re-extinction. Childhood maltreatment may alter the development of fear extinction and related brain activation. In particular, findings suggest that maltreatment-exposed youth do not discriminate between threat and safety in an age-expected manner. Altered hippocampal and frontoamygdala function may underlie difficulties learning or integrating environmental cues signaling safety that could increase risk for mental health disorders during development.

Authors

• Dylan Gee, Yale University
  Presenting Author

• Natalie Colich, University Of Washington
  Non-Presenting Author

• Margaret A. Sheridan, University of North Carolina at Chapel Hill
  Non-Presenting Author

• Daniel S. Pine, National Institutes of Health
  Non-Presenting Author

• Katie McLaughlin, Harvard University
  Non-Presenting Author