Abnormal processing of interpersonal cues during an aggressive encounter in women with borderline personality disorder: Neural and behavioral findings.

Inappropriate aggression is a prominent and clinically relevant interpersonal dysfunction of individuals with borderline personality disorder (BPD). Previous studies have shown that individuals with BPD interpret interpersonal signals in a hostile manner, but it is uncertain how this negativity bias impacts decision-making during aggressive encounters. In the present neuroimaging study, 48 medication-free women with BPD and 28 age- and intelligence-matched women played the Social Threat Aggression Paradigm (STAP), a competitive reaction time task in which the winner delivers an aversive sound blast to the loser. Crucially, in the STAP the alleged opponent displays either an angry or neutral facial expression at the beginning of each trial and selects increasingly loud blasts in order to provoke participants. Relative to healthy controls, women with BPD differentiated less between angry and neutral facial expressions, both in terms of aggressive behavior and of activity in medial prefrontal cortex, amygdala, and temporal pole. On the one hand, and contrary to our hypotheses, neural and behavioral responses to angry faces were reduced in women with BPD compared to healthy women. On the other hand, provocation heightened subsequent amygdala responses to neutral faces in BPD, and this was in turn associated with aggressive behavior, supporting a default negativity bias in BPD. The neurocognitive processes by which these alterations might guide aggressive behavior irrespective of interpersonal cues are presented and discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

A Mechanism-Based Approach to Anti-Aggression Psychotherapy in Borderline Personality Disorder: Group Treatment Affects Amygdala Activation and Connectivity.

Aggression is highly prevalent in borderline personality disorder (BPD). Previous studies have identified specific biobehavioral mechanisms underlying aggression in BPD, threat sensitivity being among them. We composited the mechanism-based anti-aggression psychotherapy (MAAP) in order to target these specific mechanisms, and MAAP was found to be superior to non-specific supportive psychotherapy (NSSP) in reducing aggressive behavior. In the present study, we investigated whether underlying brain mechanisms expected to be involved were affected by MAAP. To this end, n = 33 patients with BPD and overt aggressive behavior (n = 20 in MAAP, n = 13 in NSSP) and n = 25 healthy participants took part in a functional magnetic resonance imaging emotional face-matching task before and after treatment, or at a similar time interval for controls. Overt aggressive behavior was assessed using the overt aggression scale, modified. Results showed a decrease in amygdala activation in response to facial stimuli after MAAP, whereas an increase in amygdala activation was found after NSSP. Furthermore, in the MAAP group, connectivity between amygdala and dorsomedial prefrontal cortex increased from pre- to post-treatment compared to the NSSP group. Hence, the results suggest an impact of MAAP on brain mechanisms underlying the salience circuit in response to threat cues.

Impact of a Mechanism-Based Anti-Aggression Psychotherapy on Behavioral Mechanisms of Aggression in Patients With Borderline Personality Disorder.

Introduction: Aggressive behavior is highly prevalent in patients with borderline personality disorder (BPD) and represents a major burden for patients and their environment. Previous studies have hypothesized threat hypersensitivity, among other mechanisms, as a biobehavioral mechanism underlying aggressive behavior in patients with BPD. The effects of a 6-week mechanism-based anti-aggression psychotherapy (MAAP) for the group setting were tested in comparison to the effects of a non-specific supportive psychotherapy (NSSP) on this hypothesized mechanism and their relation to the effects on aggressive behavior. Methods: To assess mechanisms of reactive aggression, 38 patients with BPD (20 in MAAP and 18 in NSSP) and 24 healthy controls participated in an emotion classification task before and after therapy or at a similar interval of 7 weeks for controls, respectively. In addition, current reactive aggressive behavior was assessed by the externally directed overt aggression score of the Overt Aggression Scale Modified (OAS-M) at both time points. Mixed linear models were used to test for group differences and differential treatment effects. Results: Consistent with previous findings, patients showed longer response latencies and misclassified faces as angry more often than healthy controls. Comparing pre- and post-treatment measurements, the MAAP group showed an increase in response latency in classifying angry faces, whereas the NSSP group showed a decrease in latency. Furthermore, the difference between pre- and post-treatment response latencies in classifying emotional faces correlated with the reductions in reactive aggression in the MAAP group, but not in the NSSP group or healthy controls. Conclusion: The results suggest an impact of MAAP on threat sensitivity as well as cognitive control, which has also been previously hypothesized as a biobehavioral mechanism underlying reactive aggression in patients with BPD. In addition, our findings shed light on the importance of these two biobehavioral mechanisms underlying reactive aggression as mechanisms of change addressed by MAAP. Further studies are needed to determine whether the behavioral change is stable over time and to what extent this change is related to a stable reduction in reactive aggression in a larger group of patients with BPD.

Don't Make Me Angry: Frustration-Induced Anger and Its Link to Aggression in Women With Borderline Personality Disorder.

Aggression is a prominent interpersonal dysfunction of individuals with borderline personality disorder (BPD). In BPD aggression is predominantly reactive in nature, often triggered by frustration, provocation, or social threat and is associated with intense anger and an inability to regulate this strong, negative emotion. Building on previous research, we were interested in investigating negative emotionality in general and anger in particular in women with BPD before and after frustration induction. To achieve this, 60 medication-free women with BPD and 32 healthy women rated the intensity of negative emotions (angry, frustrated, upset, embarrassed, nervous) before and after performing a Titrated Mirror Tracing Task, which reliably induces frustration and distress. As expected, women with BPD reported significantly greater intensity of negative emotions before and after frustration than healthy women. Specifically, they showed a significantly stronger frustration-induced increase in anger, while other negative emotions remained unaffected by frustration induction. This anger increase was significantly related to aggressive behavior reported in the 2 weeks prior to the experiment, as well as to the level of frustration experienced in the experiment itself, but not with emotion dysregulation. The current data confirm the important role of frustration-induced anger independent of emotion dysregulation in BPD, in particular with regard to aggression, a prominent interpersonal dysfunction of this disorder. These findings underline the importance of interventions with particular focus on anger.

An eye-tracking study of interpersonal threat sensitivity and adverse childhood experiences in borderline personality disorder.

BACKGROUND: Previous eye-tracking studies provide preliminary evidence for a hypersensitivity to negative, potentially threatening interpersonal cues in borderline personality disorder (BPD). From an etiological point of view, such interpersonal threat hypersensitivity might be explained by a biological vulnerability along with a history of early life adversities. The objective of the current study was to investigate interpersonal threat hypersensitivity and its association with adverse childhood experiences (ACE) in patients with BPD employing eye-tracking technology. METHODS: We examined a sample of 46 unmedicated, adult female patients with BPD and 25 healthy female volunteers, matched on age and intelligence, with a well-established emotion classification paradigm with angry, fearful, happy, and neutral facial expressions. ACE were assessed retrospectively with the Childhood Trauma Questionnaire. RESULTS: Patients as compared to healthy volunteers reflexively directed their gaze more quickly towards the eyes of emotional and neutral faces and did not adapt their fixation patterns according to the facial expression presented. Misclassifying emotional and neutral faces as angry correlated positively with the patients' self-reported ACE. CONCLUSIONS: Building on and extending earlier findings, our results are likely to suggest a visual hypervigilance towards the eyes of emotional and neutral facial expressions and a childhood trauma-related anger bias in patients with BPD. Given the lack of a clinical control group, the question whether these findings are specific for BPD has to remain open. Thus, further research is needed to elucidate the specificity of altered visual attention allocation and the role of ACE in anger recognition in patients with BPD.

Cortical thickness and resting-state cardiac function across the lifespan: A cross-sectional pooled mega-analysis.

Understanding the association between autonomic nervous system [ANS] function and brain morphology across the lifespan provides important insights into neurovisceral mechanisms underlying health and disease. Resting-state ANS activity, indexed by measures of heart rate [HR] and its variability [HRV] has been associated with brain morphology, particularly cortical thickness [CT]. While findings have been mixed regarding the anatomical distribution and direction of the associations, these inconsistencies may be due to sex and age differences in HR/HRV and CT. Previous studies have been limited by small sample sizes, which impede the assessment of sex differences and aging effects on the association between ANS function and CT. To overcome these limitations, 20 groups worldwide contributed data collected under similar protocols of CT assessment and HR/HRV recording to be pooled in a mega-analysis (N = 1,218 (50.5% female), mean age 36.7 years (range: 12-87)). Findings suggest a decline in HRV as well as CT with increasing age. CT, particularly in the orbitofrontal cortex, explained additional variance in HRV, beyond the effects of aging. This pattern of results may suggest that the decline in HRV with increasing age is related to a decline in orbitofrontal CT. These effects were independent of sex and specific to HRV; with no significant association between CT and HR. Greater CT across the adult lifespan may be vital for the maintenance of healthy cardiac regulation via the ANS-or greater cardiac vagal activity as indirectly reflected in HRV may slow brain atrophy. Findings reveal an important association between CT and cardiac parasympathetic activity with implications for healthy aging and longevity that should be studied further in longitudinal research.

Cognitive and Affective Theory of Mind in Female Patients With Borderline Personality Disorder.

Empirical studies have identified deficits in cognitive and affective theory of mind (ToM) in patients with borderline personality disorder (BPD), but results remain heterogeneous and not much is known about the role of childhood trauma. The current study assessed cognitive and affective ToM in 80 patients with BPD and 41 healthy controls in a false-belief cartoon task. Childhood trauma was measured with the Childhood Trauma Questionnaire (CTQ). Patients with BPD responded slower in all experimental conditions in false-belief situations, but not when false beliefs were resolved; made more errors in the cognitive ToM condition; and reported worse affective states more often in and after false-belief situations. No significant correlations between ToM and childhood trauma could be found. The current study revealed deficits in cognitive and affective ToM in patients with BPD that may be related to a more negative affective state raised by the false-belief stories.

Whole-brain functional connectivity during script-driven aggression in borderline personality disorder.

OBJECTIVE: Intense anger and anger-related aggression are frequently reported by patients with borderline personality disorders (BPD). Recent results suggest that anger-related aggression and its control is associated with a complex interplay of different neural systems in BPD. To further investigate this, we complement standard activation and seed-based connectivity analyses by examining whole-brain changes in functional connectivity during anger and reactive aggression in BPD. METHODS: We reanalyzed functional MRI data from 33 women with BPD, all of them fulfilling BPD criterion 8, "anger proneness", according to DSM-IV, and 30 healthy women. Subjects performed a script-driven imagery task consisting of four phases: baseline, anger-induction by a narrative of interpersonal rejection, a narrative of directing physical aggression towards others, and relaxation. We used a data-driven, spatially constrained spectral clustering approach to parcellate the brain into 200 regions. For each script-phase and subject, we computed the full connectivity matrix using wavelet coefficient correlations in the 0.05-0.10 Hz range. We calculated the individual increase in connectivity from baseline to the anger-induction and physical aggression phases by subtracting the corresponding connectivity matrices per subject, as well as the increase and decrease from the anger-induction to the aggression phase. We then applied permutation-based sampling to determine a combined threshold on the strength of individual connections and the size of the discovered networks for these difference matrices. RESULTS: We discovered a single, large network showing a significantly stronger increase in connectivity from baseline to the aggression phase in female patients with BPD compared to healthy women. This network consisted of regions in the anterior and posterior cingulate cortex, precuneus, dorsomedial prefrontal cortex, superior and middle temporal gyrus, hippocampus, insula, ventrolateral and dorsolateral prefrontal cortex, superior parietal lobe, thalamus, precentral and postcentral gyrus, caudate, pallidum, cerebellum, middle occipital lobe, lingual gyrus, calcarine sulcus, and fusiform gyrus. Hub regions with highest node centrality were found in the right caudate and left thalamus. We found no significant differences for the increase of connectivity from baseline to anger-induction, as well as for the increase or decrease from the anger-induction to the aggression phase. CONCLUSIONS: We identified a large network showing a significantly stronger increase in connectivity from baseline to the aggression phase in female patients with BPD compared to healthy women. The regions constituting this network belong to four previously described functional networks: The frontoparietal cognitive control network, the extended default mode network, the visual system, and the motor system. This stronger increase in connectivity between regions of different functional brain systems associated with cognitive control of behavior, socio-affective and self-referential thinking, as well as salience processing and emotion regulation, visual perception, and action is mediated via hubs in the thalamus and caudate, i.e., core components of the thalamocorticostriatal motor loop essential for action selection and initiation. These findings suggest increased interaction of prefrontal cognitive control processes with thalamocorticostriatal action-selection processes in female patients with BPD during the processing of aggressive action impulses, which are facilitated by states of high emotional salience and associated processes of self-referential and social processing, and ineffective emotion regulation.

Out of control? Acting out anger is associated with deficient prefrontal emotional action control in male patients with borderline personality disorder.

Difficulty in anger control and anger-related aggressive outbursts against others are frequently reported by patients with borderline personality disorder (BPD). Although male sex is a known predictor for aggression, hardly any study has addressed the neural correlates of deficient anger control in male patients with BPD. Building on previous reports in female BPD, we investigated the involvement of lateral antero- and dorsal prefrontal cortex in the control of fast emotional actions and its relation to self-reported tendencies to act out anger. 15 medication-free male patients with BPD and 25 age- and intelligence-matched healthy men took part in a social Approach-Avoidance task in the MR-scanner. This task allows the measurement of neural correlates underlying the control of fast behavioral tendencies to approach happy and avoid angry faces. Hypothesis-driven region-of-interest and exploratory whole brain analyses were used to test for activations of antero- and dorsolateral prefrontal regions and their relation with the amygdala during emotional action control as well as their association with self-reported anger out in male patients with BPD and healthy volunteers. Male patients with BPD showed reduced anterolateral prefrontal activations during emotional action control compared to healthy volunteers. Furthermore, anger out was negatively related to antero- and dorsolateral prefrontal activations, while it was positively related to amygdala activity in male patients with BPD. The current results suggest the involvement of antero- and dorsolateral prefrontal regions in controlling and overriding fast emotional actions. Deficits in lateral prefrontal emotion control seem to be a common neural mechanism underlying anger-related aggression. This article is part of the Special Issue entitled 'Current status of the neurobiology of aggression and impulsivity'.

Heightened Salience of Anger and Aggression in Female Adolescents With Borderline Personality Disorder-A Script-Based fMRI Study.

Background: Anger and aggression belong to the core symptoms of borderline personality disorder. Although an early and specific treatment of BPD is highly relevant to prevent chronification, still little is known about anger and aggression and their neural underpinnings in adolescents with BPD. Method: Twenty female adolescents with BPD (age 15-17 years) and 20 female healthy adolescents (age 15-17 years) took part in this functional magnetic resonance imaging (fMRI) study. A script-driven imagery paradigm was used to induce rejection-based feelings of anger, which was followed by descriptions of self-directed and other-directed aggressive reactions. To investigate the specificity of the neural activation patterns for adolescent patients, results were compared with data from 34 female adults with BPD (age 18-50 years) and 32 female healthy adults (age 18-50 years). Results: Adolescents with BPD showed increased activations in the left posterior insula and left dorsal striatum as well as in the left inferior frontal cortex and parts of the mentalizing network during the rejection-based anger induction and the imagination of aggressive reactions compared to healthy adolescents. For the other-directed aggression phase, a significant diagnosis by age interaction confirmed that these results were specific for adolescents. Discussion: The results of this very first fMRI study on anger and aggression in adolescents with BPD suggest an enhanced emotional reactivity to and higher effort in controlling anger and aggression evoked by social rejection at an early developmental stage of the disorder. Since emotion dysregulation is a known mediator for aggression in BPD, the results point to the need of appropriate early interventions for adolescents with BPD.

Interpersonal Threat Sensitivity in Borderline Personality Disorder: An Eye-Tracking Study.

Threat sensitivity is a prominent predictor of interpersonal dysfunctions in borderline personality disorder (BPD), leading to intense, aversive feelings of threat and eventually dysfunctional behaviors, such as aggression. In the present study, BPD patients and healthy volunteers classified angry, fearful, neutral, and happy faces presented for 150 ms or 5,000 ms to investigate initial saccades and facial scanning. Patients more often wrongly identified anger, responded slower to all faces, and made faster saccades towards the eyes of briefly presented neutral faces and slower saccades away from fearful eyes compared with healthy volunteers. Latency of initial saccades and fixation duration correlated negatively with the patients' aggressiveness. Supporting previous results, BPD patients did not experience general deficits in facial emotion processing, but a specific hypersensitivity for and deficits in detailed evaluation of threat cues, which was particularly enhanced in aggressive patients. Interventions might benefit from relocating attention towards positive information and detailed evaluation of social cues.