Trustworthiness appraisal deficits in borderline personality disorder are associated with prefrontal cortex, not amygdala, impairment

Borderline Personality Disorder (BPD) is associated with sensitivity to signals of interpersonal threats and misplaced trust in others. The amygdala, an integral part of the threat evaluation and response network, responds to both fear- and trust-related stimuli in non-clinical samples, and is more sensitive to emotional stimuli in BPD compared to controls. However, it is unknown whether the amygdalar response can account for deficits of trust and elevated sensitivity to interpersonal threat in BPD. Facial stimuli were presented to 16 medication-free women with BPD and 17 demographically-matched healthy controls (total n = 33). Participants appraised fearfulness or trustworthiness of the stimuli while BOLD fMRI was obtained. Though BPD participants judged stimuli as less trustworthy compared to controls, trustworthiness did not correlate with amygdalar activity in either group. Trustworthiness correlated with prefrontal regional activity in the insula and lateral prefrontal cortex. Prefrontal BOLD activity while appraising trustworthiness was smaller in BPD compared to controls, and the size of the reduction was proportional to each participant's response bias. Neural substrates of trustworthiness appraisal are associated with the lateral prefrontal cortex and insula, not amygdala, suggesting that untrustworthy stimuli do not elicit a subcortical threat response. Current models of BPD and its treatment may need to include a focus on improving impairments in frontally mediated trustworthiness appraisal in addition to amygdala- driven emotional hyper-reactivity. •BPD is associated with sensitivity to signals of interpersonal betrayal and misplaced trust in others.•BPD subjects judged faces to be less trustworthy than controls.•Amygdala activity did not correlate with trustworthiness, but was modulated robustly by fearfulness of the stimulus.•Prefrontal cortex, not amygdala, was modulated by trustworthiness.•BPD was associated with reduced prefrontal activity, and the reduction was proportional to each individual’s response bias.