Nearly 65% of youth experience trauma, and up to one-third of youth with trauma exposure face profound mental health sequelae. There remains a need to elucidate factors that contribute to psychopathology following trauma exposure, and to optimize interventions for youth who do not benefit sufficiently from existing treatments. Here, we probe safety signal learning (SSL), which is a mechanism of fear reduction that leverages learned safety to inhibit fear in the presence of threat-associated stimuli and has been shown to attenuate fear via a hippocampal–cingulate––specifically, a dorsal anterior cingulate cortex (dACC)––pathway.

The present study used behavioral and task-based functional magnetic resonance imaging data to examine age-related associations between interpersonal trauma exposure and the behavioral and neural correlates (ie, activation and functional connectivity) of SSL in a group of 102 youth (aged 9-19 years; 46 female, 56 male) with (n = 52) and without (n = 50) interpersonal trauma exposure. Primary analyses examined anterior hippocampal activation and anterior hippocampus–dACC functional connectivity. Exploratory analyses examined centromedial amygdala (CMA) and laterobasal amygdala (LBA) activation and anterior hippocampal, CMA, and LBA functional connectivity with additional anterior cingulate subregions (ie, subgenual anterior cingulate cortex [sgACC] and rostral anterior cingulate cortex [rosACC]).

Both youth with and without interpersonal trauma exposure successfully learned conditioned safety, which was determined by using self-report of contingency awareness. Youth with interpersonal trauma exposure (relative to youth in the comparison group) exhibited age-specific patterns of lower hippocampal activation (F_2,96 = 3.75, p_FDR = .049, η_p² = 0.072), and, in exploratory analyses, showed heightened centromedial amygdala activation (F_1,96 = 5.37, p_FDR = .046, η_p² = 0.053) and an age-related decrease in hippocampal–sgACC functional connectivity during SSL (F_1,94 = 10.68, p_FDR = .015, η_p² = 0.102). We also show that hippocampal–sgACC functional connectivity mediated the association between interpersonal trauma exposure and post-traumatic stress disorder symptoms in an age-specific manner in the overall sample.

Together, these findings suggest that although age- and trauma-specific differences in the neural correlates of SSL may relate to the development of psychopathology, youth with interpersonal trauma exposure demonstrate successful learning of conditioned safety over time.

Childhood trauma is a major risk factor for the development of psychiatric conditions such as posttraumatic stress disorder (PTSD). Using cross-sectional analysis, this study examined age-related differences in safety signal learning and its neural correlates among youth (N=102) ages 9 to 19 with and without exposure to interpersonal trauma. The authors found that youth exposed to trauma successfully learned about cues signaling safety; however, they showed age-related differences in hippocampal-frontoamygdala circuitry during safety signal learning that might relate to risk for PTSD at specific developmental stages. These findings can inform efforts to promote safety learning and optimize developmentally focused interventions for youth with PTSD.

We worked to ensure that the study questionnaires were prepared in an inclusive way. We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper received support from a program designed to increase minority representation in science.