Neural Alterations in Pavlovian Reversal Learning Link Childhood Trauma and Transdiagnostic Anxiety in Youth.

BACKGROUND:Pavlovian reversal learning (RL) is a potential pathway linking childhood trauma (CT) with psychopathology. RL describes the ability to flexibly update associations of stimuli with threat and safety based on changing contextual significance. This study aims to characterize how CT may alter the neural underpinnings of RL in youth in ways relevant to mental health. METHODS:One hundred participants aged 9-19, half with CT (i.e., interpersonal violence) exposure, completed a RL task during an fMRI scan. One previously-neutral stimulus was paired with an aversive stimulus and predicted threat (CS+); another was not and predicted safety (CS-). Then, contingencies were reversed, such that the old safety cue became the new threat cue (New CS+) and vice-versa. Regions-of-interest analyses and nonparametric mediation models with 10,000 simulations were used to examine patterns of neural activation and connectivity and whether they indirectly linked CT with psychopathology. RESULTS:Youth with CT displayed elevated threat RL (New CS+ > New CS-) in amygdala; reduced safety RL (New CS- > New CS+) in canonical safety-learning regions, including ventromedial prefrontal cortex, hippocampus, and posterior parahippocampal gyrus (PHG); and elevated hippocampus-anterior cingulate cortex connectivity during safety RL. Critically, there were indirect effects of CT on transdiagnostic psychopathology through reduced safety RL in hippocampus and PHG, such that trauma-related reductions in discrimination between reversed cues were associated with lower levels of generalized anxiety and panic symptoms, findings driven by associations within the trauma group. CONCLUSIONS:Alterations in RL following CT during this key developmental window may reflect an environmental experience-dependent pathway to resilience.