Rejection Distress Suppresses Medial Prefrontal Cortex in Borderline Personality Disorder.

BACKGROUND: Borderline personality disorder (BPD) is characterized by an elevated distress response to social exclusion (i.e., rejection distress), the neural mechanisms of which remain unclear. Functional magnetic resonance imaging studies of social exclusion have relied on the classic version of the Cyberball task, which is not optimized for functional magnetic resonance imaging. Our goal was to clarify the neural substrates of rejection distress in BPD using a modified version of Cyberball, which allowed us to dissociate the neural response to exclusion events from its modulation by exclusionary context. METHODS: Twenty-three women with BPD and 22 healthy control participants completed a novel functional magnetic resonance imaging modification of Cyberball with 5 runs of varying exclusion probability and rated their rejection distress after each run. We tested group differences in the whole-brain response to exclusion events and in the parametric modulation of that response by rejection distress using mass univariate analysis. RESULTS: Although rejection distress was higher in participants with BPD (F1,40 = 5.25, p = .027, η2 = 0.12), both groups showed similar neural responses to exclusion events. However, as rejection distress increased, the rostromedial prefrontal cortex response to exclusion events decreased in the BPD group but not in control participants. Stronger modulation of the rostromedial prefrontal cortex response by rejection distress was associated with higher trait rejection expectation, r = -0.30, p = .050. CONCLUSIONS: Heightened rejection distress in BPD might stem from a failure to maintain or upregulate the activity of the rostromedial prefrontal cortex, a key node of the mentalization network. Inverse coupling between rejection distress and mentalization-related brain activity might contribute to heightened rejection expectation in BPD.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.