Transcutaneous auricular vagus nerve stimulation to acutely reduce emotional vulnerability and improve emotional regulation in borderline personality disorder (tVNS-BPD): study protocol for a randomized, single-blind, sham-controlled trial.

BACKGROUND: Borderline personality disorder (BPD) is considered a disorder of emotion regulation resulting from the expression of a biologically determined emotional vulnerability (that is, heightened sensitivity to emotion, increased emotional intensity/reactivity, and a slow return to emotional baseline) combined with exposure to invalidating environments. Vagal tone has been associated with activity in cortical regions involved in emotion regulation and a lower resting state of vagal tone has been observed in BPD patients relative to healthy controls. Non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) has been shown to reduce temper outbursts in adults with Prader-Willi Syndrome, to enhance recognition of emotions in healthy students, and to improve depressive and anxiety symptoms. Furthermore, a single session of taVNS has been shown to acutely alter the recognition of facial expressions of negative valence in adolescents with MDD and increase emotion recognition in controls. However, the effect of taVNS on emotional vulnerability and regulation in individuals diagnosed with BPD has not been investigated. Our aims are to determine if taVNS is effective in acutely reducing emotional vulnerability and improve emotional regulation in BPD patients. METHODS: Forty-two patients will be randomized to a single session of taVNS or sham-taVNS while going through an affect induction procedure. It will consist of the presentation of one neutral and three negative affect-evoking 4-min-long videos in sequence, each of which is followed by a 4-min post-induction period during which participants will rate the quality and intensity of their current self-reported emotions (post-induction ratings) and the perceived effectiveness in managing their emotions during the video presentation. The rating of the current self-reported emotions will be repeated after every post-induction period (recovery ratings). Mixed models with individuals as random effect will be used to investigate the ratings at each stage of the study, taking into account the repeated measures of the same individuals at baseline, pre-induction, post-induction, and recovery. DISCUSSION: The study has potential to yield new insights into the role of vagal tone in emotion dysregulation in BPD and offer preliminary data on the effectiveness of taVNS as a possible non-invasive brain stimulation to treat a core symptom of BPD. TRIAL REGISTRATION: ClinicalTrials.gov NCT05892900. Retrospectively registered on Jun 07, 2023.

Borderline personality disorder stigma: Examining the effects of diagnostic disclosure, behavior, and gender as sources of stigma in the general population.

Borderline personality disorder (BPD) is a severe mental disorder characterized by a pervasive pattern of emotional and behavioral dysregulation. Dysfunction and distress may be compounded by stigmatizing beliefs held by members of the community. There is a lack of research focusing on stigmatizing beliefs about BPD held by the general population. This study addressed this gap by examining the relationship between BPD and a variety of stigma domains in a community sample. The current study explored whether (a) stigma is more strongly related to BPD symptomatic behavior or the diagnostic label of BPD, (b) attaching a diagnosis of BPD to symptomatic behavior or nonclinical behavior influences stigma, and (c) the gender of a vignette character influences the stigmatization of BPD. A total of 295 participants read vignettes and completed questionnaires assessing stigma type and intensity. Findings from the current study suggest that stigma is higher for BPD symptomatic behavior than for the diagnosis itself. Attaching a diagnostic label of BPD to BPD symptomatic behavior did not significantly impact the resultant stigma; however, the diagnosis was found to increase stigma for nonclinical behavior. Findings concerning BPD stigma and gender are in line with broader gender stereotypes. Specifically, there was greater pity for women displaying BPD behavior, whereas there was greater anger for men displaying the same behavior. BPD symptomatic behavior vignettes depicting a man also received a higher level of dangerousness and fear. Study limitations and future directions are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

DSM-5 suicidal behavior disorder: a systematic review of research on clinical utility, diagnostic boundaries, measures, pathophysiology and interventions.

Background: It has been a decade since Suicidal Behavior Disorder (SBD) was introduced in Section III of the DSM-5 under "Conditions for Further Study". SBD is chiefly characterized by a self-initiated sequence of behaviors believed at the time of initiation to cause one's own death and occurring in the last 24 months. Aims: To systematically review empirical studies on SBD to identify primary research themes and promising future research directions. Method: A search of empirical articles on SBD published between May 2013 and March 2023 was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: Screening of 73 records by two independent raters yielded 14 eligible articles. The primary research themes identified from these articles included clinical utility of SBD to predict future suicide risk, association of SBD with closely related disorders, psychometric properties of SBD measures, pathophysiology of SBD, and the effectiveness of interventions for people with SBD. Conclusion: Understanding of SBD has slowly progressed since its introduction a decade ago and has mainly been applied in research to define study groups displaying suicidal behavior. The clinical utility of SBD for predicting future suicide risk is low and more research is needed to understand measurement of the diagnosis and its distinctiveness from related disorders and other self-harming behaviors.

Perception and memory-based representations of facial emotions: Associations with personality functioning, affective states and recognition abilities.

Personality traits and affective states are associated with biases in facial emotion perception. However, the precise personality impairments and affective states that underlie these biases remain largely unknown. To investigate how relevant factors influence facial emotion perception and recollection, Experiment 1 employed an image reconstruction approach in which community-dwelling adults (N = 89) rated the similarity of pairs of facial expressions, including those recalled from memory. Subsequently, perception- and memory-based expression representations derived from such ratings were assessed across participants and related to measures of personality impairment, state affect, and visual recognition abilities. Impairment in self-direction and level of positive affect accounted for the largest components of individual variability in perception and memory representations, respectively. Additionally, individual differences in these representations were impacted by face recognition ability. In Experiment 2, adult participants (N = 81) rated facial image reconstructions derived in Experiment 1, revealing that individual variability was associated with specific visual face properties, such as expressiveness, representation accuracy, and positivity/negativity. These findings highlight and clarify the influence of personality, affective state, and recognition abilities on individual differences in the perception and recollection of facial expressions.

Pretreatment cognitive performance is associated with differential self-harm outcomes in 6 v. 12-months of dialectical behavior therapy for borderline personality disorder.

BACKGROUND: Recent findings suggest that brief dialectical behavior therapy (DBT) for borderline personality disorder is effective for reducing self-harm, but it remains unknown which patients are likely to improve in brief v. 12 months of DBT. Research is needed to identify patient characteristics that moderate outcomes. Here, we characterized changes in cognition across brief DBT (DBT-6) v. a standard 12-month course (DBT-12) and examined whether cognition predicted self-harm outcomes in each arm. METHODS: In this secondary analysis of 240 participants in the FASTER study (NCT02387736), cognitive measures were administered at pre-treatment, after 6 months, and at 12 months. Self-harm was assessed from pre-treatment to 2-year follow-up. Multilevel models characterized changes in cognition across treatment. Generalized estimating equations examined whether pre-treatment cognitive performance predicted self-harm outcomes in each arm. RESULTS: Cognitive performance improved in both arms after 6 months of treatment, with no between-arm differences at 12-months. Pre-treatment inhibitory control was associated with different self-harm outcomes in DBT-6 v. DBT-12. For participants with average inhibitory control, self-harm outcomes were significantly better when assigned to DBT-12, relative to DBT-6, at 9-18 months after initiating treatment. In contrast, participants with poor inhibitory control showed better self-harm outcomes when assigned to brief DBT-6 v. DBT-12, at 12-24 months after initiating treatment. CONCLUSIONS: This work represents an initial step toward an improved understanding of patient profiles that are best suited to briefer v. standard 12 months of DBT, but observed effects should be replicated in a waitlist-controlled study to confirm that they were treatment-specific.

GABAergic signaling in alcohol use disorder and withdrawal: pathological involvement and therapeutic potential.

Alcohol is one of the most widely used substances. Alcohol use accounts for 5.1% of the global disease burden, contributes substantially to societal and economic costs, and leads to approximately 3 million global deaths yearly. Alcohol use disorder (AUD) includes various drinking behavior patterns that lead to short-term or long-lasting effects on health. Ethanol, the main psychoactive molecule acting in alcoholic beverages, directly impacts the GABAergic system, contributing to GABAergic dysregulations that vary depending on the intensity and duration of alcohol consumption. A small number of interventions have been developed that target the GABAergic system, but there are promising future therapeutic avenues to explore. This review provides an overview of the impact of alcohol on the GABAergic system, the current interventions available for AUD that target the GABAergic system, and the novel interventions being explored that in the future could be included among first-line therapies for the treatment of AUD.

Executive functions and behavioral economic demand for cannabis among young adults: Indirect associations with cannabis consumption and cannabis use disorder.

Behavioral economic demand for cannabis is robustly associated with cannabis consumption and cannabis use disorder (CUD). However, few studies have examined the processes underlying individual differences in the relative valuation of cannabis (i.e., demand). This study examined associations between executive functions and cannabis demand among young adults who use cannabis. We also examined indirect associations of executive functions with cannabis consumption and CUD symptoms through cannabis demand. Young adults (N = 113; 58.4% female; mean age 22 years) completed a Marijuana Purchase Task. Participants also completed cognitive tasks assessing executive functions (set shifting, inhibitory control, working memory) and semistructured interviews assessing past 90-day cannabis consumption (number of grams used) and number of CUD symptoms. Poorer inhibitory control was significantly associated with greater Omax (peak expenditure on cannabis) and greater intensity (cannabis consumption at zero cost). Poorer working memory was significantly associated with lower elasticity (sensitivity of consumption to escalating cost). Lower inhibitory control was indirectly associated with greater cannabis consumption and CUD symptoms through greater Omax and intensity, and poorer working memory was indirectly associated with greater cannabis consumption and CUD symptoms through reduced elasticity. This study provides novel evidence that executive functions are associated with individual differences in cannabis demand. Moreover, these results suggest that cannabis demand could be a mechanism linking poorer executive functioning with heavier cannabis use and CUD, which should be confirmed in future longitudinal studies. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Suicide risk detection using artificial intelligence: the promise of creating a benchmark dataset for research on the detection of suicide risk.

Suicide is a leading cause of death that demands cross-disciplinary research efforts to develop and deploy suicide risk screening tools. Such tools, partly informed by influential suicide theories, can help identify individuals at the greatest risk of suicide and should be able to predict the transition from suicidal thoughts to suicide attempts. Advances in artificial intelligence have revolutionized the development of suicide screening tools and suicide risk detection systems. Thus, various types of AI systems, including text-based systems, have been proposed to identify individuals at risk of suicide. Although these systems have shown acceptable performance, most of them have not incorporated suicide theories in their design. Furthermore, directly applying suicide theories may be difficult because of the diversity and complexity of these theories. To address these challenges, we propose an approach to develop speech- and language-based suicide risk detection systems. We highlight the promise of establishing a benchmark textual and vocal dataset using a standardized speech and language assessment procedure, and research designs that distinguish between the risk factors for suicide attempt above and beyond those for suicidal ideation alone. The benchmark dataset could be used to develop trustworthy machine learning or deep learning-based suicide risk detection systems, ultimately constructing a foundation for vocal and textual-based suicide risk detection systems.

Modeling relations between event-related potential factors and broader versus narrower dimensions of externalizing psychopathology.

The organization of the Hierarchical Taxonomy of Psychopathology (HiTOP) model provides unique opportunities to evaluate whether neural risk measures operate as indicators of broader latent liabilities (e.g., externalizing proneness) or narrower expressions (e.g., antisociality and alcohol abuse). Following this approach, the current study recruited a sample of 182 participants (54% female) who completed measures of externalizing psychopathology (also internalizing) and associated traits. Participants also completed three tasks (Flanker-No Threat, Flanker-Threat, and Go/No-Go tasks) with event-related potential (ERP) measurement. Three variants of two research domain criteria (RDoC)-based neurophysiological indicators-P3 and error-related negativity (ERN)-were extracted from these tasks and used to model two latent ERP factors. Scores on these two ERP factors independently predicted externalizing factor scores when accounting for their covariance with sex-suggesting distinct neural processes contributing to the broad externalizing factor. No predictive relation with the broad internalizing factor was found for either ERP factor. Analyses at the finer-grained level revealed no unique predictive relations of either ERP factor with any specific externalizing symptom variable when accounting for the broad externalizing factor, indicating that ERN and P3 index general liability for problems in this spectrum. Overall, this study provides new insights about neural processes in externalizing psychopathology at broader and narrower levels of the HiTOP hierarchy. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

An exploratory study of functional brain activation underlying response inhibition in major depressive disorder and borderline personality disorder.

Cognitive control is associated with impulsive and harmful behaviours, such as substance abuse and suicidal behaviours, as well as major depressive disorder (MDD) and borderline personality disorder (BPD). The association between MDD and BPD is partially explained by shared pathological personality traits, which may be underpinned by aspects of cognitive control, such as response inhibition. The neural basis of response inhibition in MDD and BPD is not fully understood and could illuminate factors that differentiate between the disorders and that underlie individual differences in cross-cutting pathological traits. In this study, we sought to explore the neural correlates of response inhibition in MDD and BPD, as well as the pathological personality trait domains contained in the ICD-11 personality disorder model. We measured functional brain activity underlying response inhibition on a Go/No-Go task using functional magnetic resonance imaging in 55 female participants recruited into three groups: MDD without comorbid BPD (n = 16), MDD and comorbid BPD (n = 18), and controls with neither disorder (n = 21). Whereas response-inhibition-related activation was observed bilaterally in frontoparietal cognitive control regions across groups, there were no group differences in activation or significant associations between activation in regions-of-interest and pathological personality traits. The findings highlight potential shared neurobiological substrates across diagnoses and suggest that the associations between individual differences in neural activation and pathological personality traits may be small in magnitude. Sufficiently powered studies are needed to elucidate the associations between the functional neural correlates of response inhibition and pathological personality trait domains.

Dimensional personality impairment is associated with disruptions in intrinsic intralimbic functional connectivity.

BACKGROUND: Recently proposed alternative dimensional models of personality disorder (PD) place the severity of impairments in self and interpersonal functioning at the core of personality pathology. However, associations of these impairments with disturbances in social, cognitive, and affective brain networks remain uninvestigated. METHODS: The present study examined patterns of resting-state functional connectivity (rsFC) in a sample of 74 age- and sex-matched participants (45 inpatients with PD and 29 healthy controls). At a minimum, PD patients carried a diagnosis of borderline PD, although the majority of the sample had one or more additional PDs. rsFC patterns in the following networks were compared between groups and in association with dimensional personality impairments: default mode network (DMN)/core mentalization, frontolimbic, salience, and central executive. Further, the extent to which variation in rsFC was explained by levels of personality impairment as compared to typology-specific borderline PD symptom severity was explored. RESULTS: Relative to controls, the PD group showed disruptions in rsFC within the DMN/core mentalization and frontolimbic networks. Among PD patients, greater severity of dimensional self-interpersonal impairment was associated with stronger intralimbic rsFC. In contrast, severity of borderline PD-specific typology was not associated with any rsFC patterns. CONCLUSIONS: Disruptions in core mentalization and affective networks are present in PD. Higher intralimbic functional connectivity may underlie self-interpersonal personality impairment in PD regardless of diagnostic typology-specific PD symptoms, providing initial neurobiological evidence supporting alternative dimensional conceptualizations of personality pathology.

Improving treatment outcomes for borderline personality disorder: what can we learn from biomarker studies of psychotherapy?

PURPOSE OF REVIEW: Borderline personality disorder (BPD) is a severe and common psychiatric disorder and though evidence-based psychotherapies are effective, rates of treatment nonresponse are as high as 50%. Treatment studies may benefit from interdisciplinary approaches from neuroscience and genetics research that could generate novel insights into treatment mechanisms and tailoring interventions to the individual. RECENT FINDINGS: We provide a timely update to the small but growing body of literature investigating neurobiological and epigenetic changes and using biomarkers to predict outcomes from evidence-based psychotherapies for BPD. Using a rapid review methodology, we identified eight new studies, updating our earlier 2018 systematic review. Across all studies, neuroimaging ( n  = 18) and genetics studies ( n  = 4) provide data from 735 participants diagnosed with BPD (mean sample size across studies = 33.4, range 2-115). SUMMARY: We report further evidence for psychotherapy-related alterations of neural activation and connectivity in regions and networks relating to executive control, emotion regulation, and self/interpersonal functioning in BPD. Emerging evidence also shows epigenetic changes following treatment. Future large-scale multisite studies may help to delineate multilevel treatment targets to inform intervention design, selection, and monitoring for the individual patient via integration of knowledge generated through clinical, neuroscience, and genetics research.

Acute Effect of Physical Exercise on Negative Affect in Borderline Personality Disorder: A Pilot Study.

Background: Physical exercise is an evidence-based treatment to reduce symptoms and negative affect in several psychiatric disorders, including depressive, anxiety, and psychotic disorders. However, the effect of physical exercise on negative affect in patients with borderline personality disorder (BPD) has not yet been investigated. In this pilot study, we tested the safety, acceptability, and potential acute effects on negative affect of a single session of aerobic physical exercise in adults with BPD. Method: After completing a negative mood induction procedure, 28 adults with BPD were randomly assigned to a 20-minute single session of stationary bicycle or a control condition (emotionally neutral video). Results: No adverse effects attributed to the physical exercise were reported and it was considered acceptable to patients. Following the negative mood induction, both conditions decreased the level of negative affect with a medium effect size but there was no significant difference between them. Conclusion: The results suggest that a single 20-minute session of physical exercise does not produce a reduction of negative affect in BPD. Future research should consider the duration and intensities of physical exercise with the greatest potential to reduce negative affect both acutely and in a more prolonged manner in this patient group.

The transdiagnostic relationship of cumulative lifetime stress with memory, the hippocampus, and personality psychopathology.

Stress has a detrimental impact on memory, the hippocampus, and psychological health. Psychopathology research on stress has centered mainly on psychiatric diagnoses rather than symptom dimensions, and less attention has been given to the neurobiological factors through which stress might be translated into psychopathology. The present work investigates the transdiagnostic relationship of cumulative stress with episodic memory and the hippocampus (both structure and function) and explores the extent to which stress mediates the relationship between personality psychopathology and hippocampal size and activation. Cumulative lifetime stress was assessed in a sample of females recruited to vary in stress exposure and severity of personality psychopathology. Fifty-six participants completed subjective and objective tests of episodic memory, a T2-weighted high-resolution magnetic resonance imaging (MRI) scan of the medial-temporal lobe, and functional MRI (fMRI) scanning during a learning and recognition memory task. Higher cumulative stress was significantly related to memory complaints (but not episodic memory performance), lower bilateral hippocampal volume, and greater encoding-related hippocampal activation during the presentation of novel stimuli. Furthermore, cumulative stress significantly mediated the relationship between personality psychopathology and both hippocampal volume and activation, whereas alternative mediation models were not supported. The findings suggest that structural and functional activation differences in the hippocampus observed in case-control studies of psychiatric diagnoses may share cumulative stress as a common factor, which may mediate broadly reported relationships between psychopathology and hippocampal structure and function.

Medial prefrontal activity during self-other judgments is modulated by relationship need fulfillment.

The medial prefrontal cortex (MPFC) plays an important role in representing semantic self-knowledge. Studies comparing semantic self-judgments with judgments of close others suggest that interpersonal closeness may influence the degree to which the MPFC differentiates self and other. We used optical neuroimaging to examine if support for competence, relatedness, and autonomy from relationship partners moderates MPFC activity during a personality judgment task. Participants (N = 109) were asked to judge the descriptive accuracy of trait adjectives for both themselves and a friend. Participants who reported lower need fulfillment with their friend showed elevated activity only in the self-judgment condition; in contrast, participants who reported higher need fulfillment with their friend showed similarly high levels of MPFC activity across the conditions. These results are consistent with the idea that the MPFC differentially represents others on the basis of the need fulfillment experienced within the relationship.

Interpersonal traits and the neural representations of cognitive control in the prefrontal cortex.

Adaptive interpersonal functioning relies on the effectiveness of behavioral and neural systems involved in cognitive control. Whether different subcomponents of cognitive control and their neural representations are associated with distinctive interpersonal dispositions has yet to be determined. The present study investigated the relationships between prefrontal cortex (PFC) activation associated with two subcomponents of cognitive control and individual differences in interpersonally relevant traits and facets within the Five-Factor Model of personality. Undergraduate participants (n = 237) provided self-ratings of interpersonal traits and underwent functional near-infrared spectroscopy to measure activation in regions-of-interest linked to subcomponents of cognitive control: the right lateral PFC and its involvement in response selection and inhibition/suppression (RS) during a go/no-go task, and the left lateral PFC associated with goal selection, updating, representation, and maintenance (GS) on a tower planning task. Multilevel models revealed that during both RS and GS, Neuroticism and Extraversion were associated with lower and higher levels of activation, respectively. Higher Agreeableness was related to lower activation during RS but also with greater activation during GS. More narrowly defined interpersonal facets subsumed within the broader trait domains were differentially associated with RS- and GS-related neural responses. Taken together, these findings highlight potential avenues of future research to better understand the ways in which the neural processes that subserve cognitive control may underlie interpersonal dispositions.

Executive functioning in adults with borderline personality disorder and first-degree biological relatives.

OBJECTIVES: Behavioural dysregulation is a heritable core symptom domain in borderline personality disorder (BPD) that is likely influenced by the integrity of executive functions (EFs). However, the extent to which familial risk for BPD confers decrement to EFs has yet to be comprehensively studied. METHODS: In this family study, probands with BPD (n = 73), first-degree biological relatives (n = 65), and healthy controls without psychiatric diagnoses (n = 77) were assessed in abstraction, attentional vigilance, working memory, cognitive flexibility, interference resolution, planning, problem solving, and response inhibition. RESULTS: In univariate analyses, probands demonstrated lower response inhibition than relatives. Comparatively, discriminant function analyses revealed that lower interference resolution and response inhibition jointly discriminated probands from relatives and controls, whereas a combination of less efficient problem solving and difficulty manipulating mental information discriminated probands and relatives from controls. Moreover, the subset of psychiatrically non-affected relatives demonstrated a pattern of resilience to psychiatric morbidity substantiated by stronger response inhibition and abstraction abilities despite less efficient problem solving. CONCLUSIONS: Familial risk for BPD is represented predominantly by a pattern of problem-solving and working memory deficits. Resilience to a psychiatric disorder in non-affected relatives reflects both EF weaknesses and strengths, highlighting potential protective factors that should be considered in future neurocognitive research on BPD families.

Stressed, sick, and sad: Neuroendoimmune pathways between subjective lifetime stress and depression.

Disruptions in stress-sensitive biological systems, notably the immune system and hypothalamic-pituitary-adrenal axis, are strongly implicated in depression, and disturbances in these neuroendoimmune systems could reflect potential pathways through which experiences of stress are translated into depression. To characterize the links between stress and depression, the present study investigated whether neuroendoimmune activity mediates the relationship between perceived stress and depressive symptoms in 59 medically healthy adult females with varying levels of depression. Consistent with hypotheses, both greater perceived stress and higher concentrations of the proinflammatory immune marker, interleukin-6 (IL-6), were associated with greater depressive symptoms. Although neuroendoimmune activity did not significantly mediate the relationship between lifetime perceived stress and depressive symptoms, when considered together, elevated concentrations of IL-6 and lower free cortisol mediated the relationship between severity of childhood stress and current depressive symptoms. These findings shed light on how early life stress may be translated into adulthood depression.

Facial Emotion Perception in Families Affected With Borderline Personality Disorder.

Emotion perception biases may precipitate problematic interpersonal interactions in families affected with borderline personality disorder (BPD) and lead to conflictual relationships. In the present study, the authors investigated the familial aggregation of facial emotion recognition biases for neutral, happy, sad, fearful, and angry expressions in probands with BPD (n = 89), first-degree biological relatives (n = 67), and healthy controls (n = 87). Relatives showed comparable accuracy and response times to controls in recognizing negative emotions in aggregate and most discrete emotions. For sad expressions, both probands and relatives displayed slower response latencies, and they were more likely than controls to perceive sad expressions as fearful. Nonpsychiatrically affected relatives were slower than controls in responding to negative emotional expressions in aggregate, and fearful and sad facial expressions more specifically. These findings uncover potential biases in perceiving sad and fearful facial expressions that may be transmitted in families affected with BPD.

Facial Emotion Perception in Borderline Personality Disorder: Differential Neural Activation to Ambiguous and Threatening Expressions and Links to Impairments in Self and Interpersonal Functioning.

BACKGROUND: Many individuals with borderline personality disorder (BPD) perceive emotional expressions in faces intended to convey no emotion and display a heightened sensitivity to facial expressions conveying threat, such as fear. In BPD, the amygdala activates in response to ambiguous and threatening facial expressions, although the differential sensitivity of this brain region to higher and lower intensities of fearful expressions and the relationship of this neural activity to personality impairments have not yet been investigated. METHODS: In the present study, we examined brain activation during an implicit facial emotion task with neutral faces and fearful expressions displayed at 50% and 100% intensity in patients with BPD (n=45) and healthy controls (HC; n=25). RESULTS: On neutral faces, higher brain activation was found in BPD compared to HC in the right temporal pole, amygdala, hippocampus, pallidum, and orbitofrontal cortex, whereas no significant whole-brain group differences were observed for either intensity of fearful expressions. A region-of-interest analysis focused on the amygdala-hippocampal complex showed greater activation for neutral and 50%-intensity fearful faces in BPD. Severity of personality impairment in the domains of empathy and identity were associated with higher precuneus activity during neutral and 100%-fearful face processing. LIMITATIONS: Brain activation differences of this naturalistic severely ill inpatient sample may be influenced by comorbid Axis-I disorders often seen in samples of BPD. CONCLUSIONS: These findings suggest a heightened amygdala-hippocampal response to neutral faces and moderate-intensity fearful expressions in BPD, while self and interpersonal impairments are associated with task-based activations in regions implicated in self-referential processes.