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1.  Trait anxiety modulates fronto-limbic processing of emotional interference in borderline personality disorder 
Previous studies of cognitive alterations in borderline personality disorder (BPD) have yielded conflicting results. Given that a core feature of BPD is affective instability, which is characterized by emotional hyperreactivity and deficits in emotion regulation, it seems conceivable that short-lasting emotional distress might exert temporary detrimental effects on cognitive performance. Here we used functional magnetic resonance imaging (fMRI) to investigate how task-irrelevant emotional stimuli (fearful faces) affect performance and fronto-limbic neural activity patterns during attention-demanding cognitive processing in 16 female, unmedicated BPD patients relative to 24 age-matched healthy controls. In a modified flanker task, emotionally negative, socially salient pictures (fearful vs. neutral faces) were presented as distracters in the background. Patients, but not controls, showed an atypical response pattern of the right amygdala with increased activation during emotional interference in the (difficult) incongruent flanker condition, but emotion-related amygdala deactivation in the congruent condition. A direct comparison of the emotional conditions between the two groups revealed that the strongest diagnosis-related differences could be observed in the dorsal and, to a lesser extent, also in the rostral anterior cingulate cortex (dACC, rACC) where patients exhibited an increased neural response to emotional relative to neutral distracters. Moreover, in the incongruent condition, both the dACC and rACC fMRI responses during emotional interference were negatively correlated with trait anxiety in the patients, but not in the healthy controls. As higher trait anxiety was also associated with longer reaction times (RTs) in the BPD patients, we suggest that in BPD patients the ACC might mediate compensatory cognitive processes during emotional interference and that such neurocognitive compensation that can be adversely affected by high levels of anxiety.
doi:10.3389/fnhum.2013.00054
PMCID: PMC3585713  PMID: 23459637
borderline personality disorder; cognition-emotion interaction; anxiety; fMRI; amygdala; anterior cingulate cortex
2.  Hypersensitivity in Borderline Personality Disorder during Mindreading 
PLoS ONE  2012;7(8):e41650.
Background
One of the core symptoms of borderline personality disorder (BPD) is the instability in interpersonal relationships. This might be related to existent differences in mindreading between BPD patients and healthy individuals.
Methods
We examined the behavioural and neurophysiological (fMRI) responses of BPD patients and healthy controls (HC) during performance of the ‘Reading the Mind in the Eyes’ test (RMET).
Results
Mental state discrimination was significantly better and faster for affective eye gazes in BPD patients than in HC. At the neurophysiological level, this was manifested in a stronger activation of the amygdala and greater activity of the medial frontal gyrus, the left temporal pole and the middle temporal gyrus during affective eye gazes. In contrast, HC subjects showed a greater activation in the insula and the superior temporal gyri.
Conclusion
These findings indicate that BPD patients are highly vigilant to social stimuli, maybe because they resonate intuitively with mental states of others.
doi:10.1371/journal.pone.0041650
PMCID: PMC3411703  PMID: 22870240
3.  Mental State Decoding Abilities in Young Adults With Borderline Personality Disorder Traits 
Personality disorders  2011;2(2):98-112.
Previous studies have demonstrated that patients with borderline personality disorder (BPD) tend to misattribute malevolence to benign social stimuli, including facial expressions. Yet, facial emotion recognition studies examining those with BPD have yielded mixed results, with some studies showing impaired accuracy and others demonstrating enhanced accuracy in the recognition of emotions or mental states. The current study examined the ability to decode mental states from photographs of just the eye region of faces in a nonclinical sample of young adults who exhibited BPD traits (high BPD) compared with those who did not (low BPD). Group differences in mental state decoding ability depended on the valence of the stimuli. The high-BPD group performed better for negative stimuli compared with the low-BPD group, but did not perform significantly different from the low-BPD group for stimuli of neutral or positive valence. The high-BPD group also demonstrated a response bias for attributing negative mental states to facial stimuli. In addition, findings suggested that the group difference in accuracy for negative stimuli could not be explained by response bias, because the group difference in response bias for negative stimuli did not reach significance. These findings suggest that BPD traits may be associated with enhanced ability to detect negative emotions and a bias for attributing negative emotions to nonnegative social stimuli.
doi:10.1037/a0020011
PMCID: PMC3257028  PMID: 22247796
borderline personality disorder; mental state decoding; emotion recognition; response bias; Reading the Mind in the Eyes Test
4.  Anger, preoccupied attachment, and domain disorganization in borderline personality disorder 
Emotional dysregulation and attachment insecurity have been reported in borderline personality disorder (BPD). Domain disorganization, evidenced in poor regulation of emotions and behaviors in relation to the demands of different social domains, may be a distinguishing feature of BPD. Understanding the interplay between these factors may be critical for identifying interacting processes in BPD and potential subtypes of BPD. Therefore, we examined the joint and interactive effects of anger, preoccupied attachment, and domain disorganization on BPD traits in clinical sample of 128 psychiatric patients. The results suggest that these factors contribute to BPD both independently and in interaction, even when controlling for other personality disorder traits and Axis I symptoms. In regression analyses, the interaction between anger and domain disorganization predicted BPD traits. In recursive partitioning analyses, two possible paths to BPD were identified: high anger combined with high domain disorganization and low anger combined with preoccupied attachment. These results may suggest possible subtypes of BPD or possible mechanisms by which BPD traits are established and maintained.
doi:10.1521/pedi.2009.23.3.240
PMCID: PMC2821703  PMID: 19538080
5.  Affect Intensity and Lability: The Role of Posttraumatic Stress Disorder Symptoms in Borderline Personality Disorder 
Depression and anxiety  2011;28(5):393-399.
Background
Emotion dysregulation is likely a core psychological process underlying the heterogeneity of presentations in borderline personality disorder (BPD) and is associated with BPD symptom severity. Emotion dysregulation has also been independently associated with posttraumatic stress disorder (PTSD), a disorder that has been found to co-occur with BPD in 30.2% of cases in a nationally representative sample. However, relatively little is known about the specific relationships between emotion dysregulation and PTSD among those diagnosed with BPD. The purpose of the current study was to evaluate relations between PTSD symptom severity and negative affect intensity and affective lability among individuals with BPD.
Method
Participants were 67 individuals diagnosed with BPD (79% women; Mage = 38, SD = 10), who reported one or more DSM-IV PTSD Criterion A events.
Results
Hierarchical multiple regression analyses indicated that when examined concurrently with BPD symptom severity, PTSD symptom severity, but not BPD symptom severity, was related to negative affect intensity and affective lability. Reexperiencing symptoms uniquely predicted affective lability, and hyperarousal symptoms uniquely predicted negative affect intensity, lending additional support to emerging literature linking reexperiencing and hyperarousal symptoms with emotion dysregulation.
Conclusions
PTSD symptom severity among individuals with a BPD diagnosis is related to elevations in emotion dysregulation. It is important to evaluate whether early treatment of PTSD symptoms provided concurrently with BPD treatment leads to enhanced improvements in emotion regulation among individuals with co-occurring PTSD and BPD.
doi:10.1002/da.20798
PMCID: PMC3087148  PMID: 21538723
posttraumatic stress disorder; trauma; anxiety disorders; borderline personality disorder; emotion
6.  GENETIC COVARIANCE STRUCTURE OF THE FOUR MAIN FEATURES OF BORDERLINE PERSONALITY DISORDER 
Journal of personality disorders  2010;24(4):427-444.
The patient population of borderline personality disorder (BPD) is heterogeneous; many different combinations of BPD symptoms can lead to a BPD diagnosis. We investigated to what extent the covariance among four main components of BPD is explained by shared genetic and environmental factors. Using an extended twin design, multivariate genetic models were applied to the scales of the PAI-BOR, a self-report questionnaire tapping four main features of BPD (affective instability, identity problems, negative relationships, and self-harm). Data on the four BPD scales were available for 5,533 twins and 1,202 siblings from the Netherlands, Belgium, and Australia. The correlations among the scales ranged from 0.23 to 0.50 and were best explained by a genetic common pathway model. This model specifies that genes and environment influence the covariance between four main features of BPD in qualitatively similar ways, through a single latent factor representing the BPD construct. The heritability of the latent BPD factor was 51% and the remainder of its variance was explained by unique environmental influences. For each BPD scale, except self-harm, around 50% of its variance was explained by the latent BPD factor. The remaining variance for each of the four scales was explained by genetic (4% for affective instability to 20% for self-harm) and environmental (38% for negative relationships to 67% for self-harm) factors that were specific to each scale.
doi:10.1521/pedi.2010.24.4.427
PMCID: PMC3705216  PMID: 20695804
7.  Social Cognition in Borderline Personality Disorder: Evidence for Disturbed Recognition of the Emotions, Thoughts, and Intentions of others 
Disturbed relatedness is a core feature of borderline personality disorder (BPD), and impaired social cognition or deficits in “mentalization” are hypothesized to underlie this feature. To date, only weak empirical evidence argues for impairment in the recognition of emotions, thoughts, or intentions in BPD. Data from facial emotion recognition research indicate that these abilities are altered in BPD only if tasks are complex. The present study aims to assess social cognitive abilities in BPD. Sixty-four women with BPD and 38 healthy controls watched the “Movie for the Assessment of Social Cognition” (MASC), a newly developed film displaying social interactions, and asking for an assessment of the intentions, emotions, and thoughts of the characters. In addition, participants completed an established but less ecologically valid measure of social cognition (“Reading the Mind in the Eyes”; RME). In the RME task, BPD patients did not display impairment in social cognition compared to healthy controls. By contrast, on the more sensitive MASC, women with BPD showed significantly impaired abilities in social cognition compared to healthy controls in their recognition of emotions, thoughts, and intentions. Comorbid PTSD, intrusions, and sexual trauma negatively predicted social cognitive abilities on the more sensitive MASC. Thus, our results suggest impaired social cognitive abilities in BPD. Especially for comorbid PTSD, intrusive symptoms, and history of sexual trauma predicted poor outcomes on social cognition tasks.
doi:10.3389/fnbeh.2010.00182
PMCID: PMC2999836  PMID: 21151817
borderline personality disorder; MASC; PTSD; empathy; social cognition; theory of mind; mentalization; trauma
8.  Neuronal correlates of social cognition in borderline personality disorder 
Patients with borderline personality disorder (BPD) have severe problems in social interactions that might be caused by deficits in social cognition. Since the findings about social-cognitive abilities in BPD are inhomogeneous, ranging from deficits to superior abilities, we aimed to investigate the neuronal basis of social cognition in BPD. We applied a paradigm with three social cognition tasks, differing in their complexity: basal processing of faces with a neutral expression, recognition of emotions, and attribution of emotional intentions (affective ToM). A total of 13 patients with BPD and 13 healthy matched controls (HCs) were included in a functional magnet resonance imaging study. BPD patients showed no deficits in social cognition on the behavioral level. However, while HCs showed increasing activation in areas of the mirror neuron system with increasing complexity in the social-cognitive task, BPD patients had hypoactivation in these areas and hyperactivation in the amygdala which were not modulated by task complexity. This activation pattern seems to reflect an enhanced emotional approach in the processing of social stimuli in BPD that allows good performance in standardized social-cognitive tasks, but might be the basis of social-cognitive deficits in real-life social interactions.
doi:10.1093/scan/nss028
PMCID: PMC3682436  PMID: 22362841
borderline personality disorder; social cognition; functional magnetic resonance imaging; mirror neuron system; amygdala
9.  Potentiated amygdala response to repeated emotional pictures in borderline personality disorder 
Biological psychiatry  2012;72(6):448-456.
Background
Borderline personality disorder (BPD) is characterized by an inability to regulate emotional responses. The amygdala is important in learning about the valence (goodness and badness) of stimuli and has been reported to function abnormally in BPD.
Methods
Event-related functional MRI (fMRI) was employed in three groups: unmedicated BPD (n=33) and schizotypal personality disorder (SPD;n=28) participants and healthy controls (n=32) during a task involving an intermixed series of unpleasant, neutral, and pleasant pictures each presented twice within their respective trial block/run. The amygdala was hand-traced on each participant’s structural-MRI scan which was co-registered to their BOLD-scan. Amygdala responses were examined with a mixed-model MANOVA with repeated measures.
Results
Compared with both control groups, BPD patients showed greater amygdala activation, particularly to the repeated emotional but not neutral pictures and a prolonged return to baseline for the overall BOLD response averaged across all pictures. Despite amygdala overactivation, BPD patients showed a blunted response on the self-report ratings of emotional but not neutral pictures. Fewer dissociative symptoms in both patient groups were associated with greater amygdala activation to repeated unpleasant pictures.
Conclusions
The increased amygdala response to the repeated emotional pictures observed in BPD was not observed in SPD patients suggesting diagnostic specificity. This BPD-related abnormality is consistent with the well-documented clinical feature of high sensitivity to emotional stimuli with unusually strong and long-lasting reactions. The finding of a mismatch between physiological and self-report measures of emotion reactivity in BPD patients suggests they may benefit from treatments which help them recognize emotions.
doi:10.1016/j.biopsych.2012.03.027
PMCID: PMC3415575  PMID: 22560044
borderline personality disorder; schizotypal personality disorder; amygdala; emotion; fMRI; arousal; valence
10.  A Developmental Neuroscience of Borderline Pathology: Emotion Dysregulation and Social Baseline Theory 
Theoretical and empirical research has linked poor emotion regulation abilities with dysfunctional frontolimbic circuitry. Consistent with this, research on borderline personality disorder (BPD) finds that frontolimbic dysfunction is a predominant neural substrate underlying the disorder. Emotion regulation is profoundly compromised in BPD. However, BPD is also associated with broad impairment across multiple domains, including impulse control, interpersonal relationships, and cognitive functioning. To date, BPD research has focused largely on single areas of dysfunction, failing to account for overlap at either the biological or behavioral levels of analysis. We examine the literature on frontolimbic dysfunction in BPD within the context of Coan’s social baseline theory. Social baseline theory proposes that healthy human functioning is dependent upon adequate social support and that, at baseline, biological systems are adapted to operate interdependently rather than independently. The social baseline perspective is particularly useful for understanding borderline personality development because the impulsive and emotionally dysregulated behaviors common among those with BPD occur almost invariably within an interpersonal context. We discuss clinical and research implications of this work.
doi:10.1007/s10802-011-9555-x
PMCID: PMC3269568  PMID: 21845379
Borderline personality; Emotion dysregulation; Attachment; Neurobiology
11.  Early visual information processing deficit in depression with and without Borderline Personality Disorder 
Psychiatry research  2006;149(0):139-145.
Backward masking is a measure of early visual information processing usually abnormal in psychotic disorders. Previous studies of subjects with Borderline Personality Disorder have been inconsistent regarding their impairment or lack of impairment on backward masking. We examined visual backward masking performance in samples of unmedicated depressed patients with (n=12) and without (n=16) Borderline Personality Disorder, and healthy volunteers (n=18). Accuracy was poorer in depressed BPD patients, relative to both non-BPD depressed and healthy comparison subjects. As in previous studies, no differences in accuracy were found between non-BPD depressed patients and healthy comparison subjects. Differences in BPD subjects’ accuracy were most evident at the fastest ISI and were not attributable to intercurrent psychotic symptoms. Beyond these group differences, accuracy at faster ISI’s correlated with self-ratings of impulsiveness in all patients, and may be a general correlate of this trait. Poor early information processing appears to be a feature of Borderline Personality Disorder, and may play a role in the impulsive behavior that is characteristic of the disorder.
doi:10.1016/j.psychres.2006.09.014
PMCID: PMC3804900  PMID: 17097149
Backward masking; Borderline Personality Disorder; Depression; Information processing; Impulsiveness; Impulsiveness assessment
12.  Biobehavioral Reactivity to Social Evaluative Stress in Women With Borderline Personality Disorder 
Personality disorders  2012;4(2):91-100.
Several clinical theories propose that borderline personality disorder (BPD) is characterized by a biologically based affective vulnerability to intense affective experiences and impaired modulation of affective states, which might manifest in high emotional intensity, hyperreactivity, and impaired recovery to baseline. However, few studies have tested these theories based on emotional and biological responses of BPD participants in response to psychosocial stressors. This study examined cortisol, alpha-amylase, and subjective emotional reactivity to social evaluative stress among women with BPD compared with two healthy female control groups: a trait-matched (TM) group scoring similarly to the BPD group on trait measures of negative affect and impulsivity, and a non-trait-matched (NTM) group. Results generally suggested high emotional intensity and high baseline psychobiological arousal among individuals with BPD, but not emotional hyperreactivity or impaired recovery specific to the stressor. Relative to both control groups, BPD participants had higher baseline and overall subjective negative affect, higher baseline cortisol levels, and attenuated stress-related cortisol reactivity. In addition, both the BPD and TM groups had attenuated alpha-amylase reactivity in comparison to the NTM group. The differences between BPD and TM groups on most of the dependent measures suggest that emotional dysregulation in BPD is not merely an extreme variant of normative personality traits. These results suggest that women with BPD demonstrate intense and chronic negative affectivity along with high resting psychobiological arousal and attenuated psychobiological reactivity specific to laboratory stressors.
doi:10.1037/a0030117
PMCID: PMC3635672  PMID: 23244772
borderline personality disorder; emotional dysregulation; psychobiological; hypothalamicpituitary-adrenal axis; autonomic nervous system
13.  Amygdala Functional Connectivity in Young Women with Borderline Personality Disorder 
Brain Connectivity  2011;1(1):61-71.
Abstract
Borderline personality disorder (BPD) is a complex psychiatric disorder that involves the core feature of affect dysregulation. Prior neuroimaging studies have indicated that BPD patients have (1) excessive amygdala activation to negative emotion and (2) diminished frontal regulation. This study examined amygdala functional connectivity in 12 women with BPD and 12 matched healthy comparison volunteers. We explored how connectivity patterns would change in the context of processing neutral, overt fear, or masked fear face expressions. Each participant underwent three 5-min fMRI scans in which they primarily viewed: (1) neutral, (2) overt fear, and (3) masked fear faces. In comparison to their healthy counterparts, young women with BPD showed (1) lower connectivity between bilateral amygdala and mid-cingulate cortex during the neutral scan; (2) higher connectivity between bilateral amygdala and rostral anterior cingulate cortex during the overt fear scan; and (3) higher right amygdala connectivity with bilateral thalamus and right caudate during the masked fear scan. Exploratory analyses revealed interesting correlations between amygdala connectivity in these conditions with multiple clinical measures. Results from the neutral scan add to the few prior connectivity studies in BPD that have been suggestive of lower fronto-limbic connectivity in BPD. However, the connectivity findings during fear processing are novel, and map onto basic research models for amygdala connectivity, that is, connections to frontal areas for overt fear processing versus connections to thalamus for automatic fear processing. Further, results suggest that BPD subjects tap into both pathways more strongly than healthy comparisons.
doi:10.1089/brain.2010.0001
PMCID: PMC3621316  PMID: 22432955
amygdala; borderline personality disorder; functional connectivity; functional neuroimaging; masked fear; overt fear
14.  Understanding the Heterogeneity of BPD Symptoms through Latent Class Analysis: Initial Results and Clinical Correlates among Inner-city Substance Users 
Psychological assessment  2010;22(2):233-245.
The current study investigated the heterogeneity of borderline personality disorder (BPD) symptoms in a sample of 382 inner-city, predominantly African-American male substance users through the use of Latent Class Analysis (LCA). A 4-class model was statistically preferred, with one class interpreted to be a “baseline” class, one class interpreted to be a “high BPD” class, and two classes interpreted as intermediate classes. As a secondary goal, we examined the resulting BPD classes in respect to relevant clinical correlates, including: temperamental vulnerabilities (affective instability, impulsivity, and interpersonal instability), childhood emotional abuse, drug choice, and co-occurring mood and anxiety disorders. The high BPD class evidenced the highest levels of the temperamental vulnerabilities and environmental stressors, the baseline class evidenced the lowest levels, and the two intermediate classes fell in between. Additionally, the high BPD class had a higher probability of cocaine and alcohol dependence, as well as mood and anxiety disorders than the baseline class. Rates of alcohol use and mood disorders for the intermediate classes fell in between the high BPD and the baseline class. Results are discussed in relation to the current diagnostic conceptualization of BPD.
doi:10.1037/a0018493
PMCID: PMC2883792  PMID: 20528051
Borderline Personality Disorder; Latent Class Analysis; Inner-City Substance Users; Diagnostic Heterogeneity
15.  Psychophysiological Assessment of Emotional Processing in Patients with Borderline Personality Disorder with and without Comorbid Substance Use 
Personality disorders  2012;4(3):203-213.
This study assessed physiological measures to study emotional dysregulation associated with borderline personality disorder (BPD). Two patient groups, individuals with BPD-only (n = 16) and individuals with BPD and co-occurring Substance Use Disorders (SUDs; n = 35), and a group of healthy controls (n = 45) were shown standardized pictures of varying valance and arousal levels while the affective modification of the startle eye-blink response, heart rate, facial electromyography (EMG; corrugator and zygomatic activity), and skin conductance responses were collected during picture presentation and during a brief recovery period. Startle data during picture presentation indicated a trend for the expected increase in startle magnitude to negative stimuli to be moderated by group status, with patients with BPD-SUD showing a lack of affective modification while the BPD-only group showing similar affective modification as controls. Heart rate data suggested lower reactivity to negative pictures for both patient groups. Differences in facial EMG responses did not provide a clear pattern and skin conductance responses were not significantly different between groups. The data did not suggest differences between groups in the recovery from the emotional stimuli. The startle and heart rate data suggest a possible hyporeactivity to emotional stimuli in BPD.
doi:10.1037/a0029777
PMCID: PMC4086455  PMID: 23088207
Borderline Personality Disorder; Emotional dysregulation; Startle Reflex; Substance use; Psychophysiology
16.  Pain sensitivity and neural processing during dissociative states in patients with borderline personality disorder with and without comorbid posttraumatic stress disorder: a pilot study 
Background
Stress-induced dissociative states involving analgesia are a common feature of borderline personality disorder (BPD) and posttraumatic stress disorder (PTSD). Our aim was to investigate the psychologic, somatosensory (pain sensitivity) and neural correlates of dissociative states in patients with these disorders.
Methods
We included 15 women with BPD who were not taking medication; 10 of these women had comorbid PTSD. While undergoing functional magnetic resonance imaging at 1.5 Tesla, participants were exposed to a script describing a personalized dissociation-inducing situation and a personalized script describing a neutral situation. We assessed dissociative psychopathology and pain sensitivity.
Results
Dissociative psychopathology scores were significantly higher and pain sensitivity was lower after the dissociation-inducing script was read compared with the neutral script. The blood oxygen level–dependent (BOLD) signal was significantly increased in the left inferior frontal gyrus (Brodmann area [BA] 9) during the presentation of the dissociation-inducing script. Regression analyses revealed positive correlations between BOLD signal and dissociative psychopathology in the left superior frontal gyrus (BA 6) and negative correlations in the right middle (BA 21) and inferior temporal gyrus (BA 20). In the subgroup of participants with comorbid PTSD, we also found increased activity in the left cingulate gyrus (BA 32) during script-driven imagery-induced dissociation, a positive correlation between dissociation scores and activity in the right and left insula (BA 13) and a negative correlation in the right parahippocampal gyrus (BA 35).
Limitations
The main limitation of this pilot study is the absence of a control group. Therefore, the results may also reflect the neural correlates of non–BPD/PTSD specific dissociative states or the neural correlates of emotionally stressful or “loaded” memories. Another limitation is the uncorrected statistical level of the functional magnetic resonance imaging results.
Conclusion
Our results showed that the script-driven imagery method is capable of inducing dissociative states in participants with BPD with and without comorbid PTSD. These states were characterized by reduced pain sensitivity and a frontolimbic activation pattern, which resembles the findings in participants with PTSD while in dissociative states.
doi:10.1503/jpn.090022
PMCID: PMC2861134  PMID: 20420768
17.  Hippocampus and amygdala volumes in patients with borderline personality disorder with or without posttraumatic stress disorder 
Background
Several studies have investigated volumetric brain changes in patients with posttraumatic stress disorder (PTSD) and borderline personality disorder (BPD). Both groups exhibit volume reductions of the hippocampus and amygdala. Our aim was to investigate the influence of comorbid PTSD on hippocampus and amygdala volumes in patients with BPD.
Methods
We compared 2 groups of unmedicated female patients with BPD (10 with and 15 without comorbid PTSD) and 25 healthy female controls. We used T1- and T2-weighted magnetic resonance images for manual tracing and 3-dimensional reconstruction of the hippocampus and amygdala.
Results
Hippocampus volumes of patients with BPD and PTSD were smaller than those of healthy controls. However, there was no significant difference between patients with BPD but without PTSD and controls. Impulsiveness was positively correlated with hippocampus volumes in patients with BPD.
Limitations
Our study did not allow for disentangling the effects of PTSD and traumatization. Another limitation was the relatively small sample size.
Conclusion
Our findings highlight the importance of classifying subgroups of patients with BPD. Comorbid PTSD may be related to volumetric alterations in brain regions that are of central importance to our understanding of borderline psychopathology.
PMCID: PMC2702446  PMID: 19568480
18.  Striatal Activity in Borderline Personality Disorder with Comorbid Intermittent Explosive Disorder: Sex Differences 
Journal of psychiatric research  2012;46(6):797-804.
Borderline Personality Disorder (BPD) is associated with behavioral and emotional dysregulation, particularly in social contexts; however, the underlying pathophysiology at the level of brain function is not well understood. Previous studies found abnormalities in frontal cortical and limbic areas suggestive of poor frontal regulation of downstream brain regions. However, the striatum, which is closely connected with the medial frontal cortices and plays an important role in motivated behaviors and processing of rewarding stimuli, has been understudied in BPD. Here we hypothesized that, in addition to frontal dysfunction, BPD patients may show abnormal striatal function. In this study, 38 BPD patients with intermittent explosive disorder (BPD-IED) and 36 healthy controls (HC) participated in the Point Subtraction Aggression Paradigm (PSAP), a computer game played with a fictitious other player. 18Fluoro-deoxyglucose positron emission tomography (FDG-PET) measured relative glucose metabolism (rGMR) within caudate and putamen in response to aggression-provoking and non-provoking versions of the PSAP. Male BPD-IED patients had significantly lower striatal rGMR than all other groups during both conditions, although male and female BPD-IED patients did not differ in clinical or behavioral measures. These sex differences suggest differential involvement of frontal-striatal circuits in BPD-IED, and are discussed in relation to striatal involvement in affective learning and social decision-making.
doi:10.1016/j.jpsychires.2012.02.014
PMCID: PMC3645307  PMID: 22464337
Borderline personality disorder; intermittent explosive disorder; striatum; aggression; positron emission tomography
19.  Functional Connectivity of Pain-Mediated Affect Regulation in Borderline Personality Disorder 
PLoS ONE  2012;7(3):e33293.
Affective instability and self-injurious behavior are important features of Borderline Personality Disorder. Whereas affective instability may be caused by a pattern of limbic hyperreactivity paired with dysfunctional prefrontal regulation mechanisms, painful stimulation was found to reduce affective arousal at the neural level, possibly underlying the soothing effect of pain in BPD.
We used psychophysiological interactions to analyze functional connectivity of (para-) limbic brain structures (i.e. amygdala, insula, anterior cingulate cortex) in Borderline Personality Disorder in response to painful stimulation. Therefore, we re-analyzed a dataset from 20 patients with Borderline Personality Disorder and 23 healthy controls who took part in an fMRI-task inducing negative (versus neutral) affect and subsequently applying heat pain (versus warmth perception).
Results suggest an enhanced negative coupling between limbic as well as paralimbic regions and prefrontal regions, specifically with the medial and dorsolateral prefrontal cortex, when patients experienced pain in addition to emotional arousing pictures. When neutral pictures were combined with painful heat sensation, we found positive connectivity in Borderline Personality Disorder between (para-)limbic brain areas and parts of the basal ganglia (lentiform nucleus, putamen), as well areas involved in self-referential processing (precuneus and posterior cingulate).
We found further evidence for alterations in the emotion regulation process in Borderline Personality Disorder, in the way that pain improves the inhibition of limbic activity by prefrontal areas. This study provides new insights in pain processing in BPD, including enhanced coupling of limbic structures and basal ganglia.
doi:10.1371/journal.pone.0033293
PMCID: PMC3299768  PMID: 22428013
20.  Evaluation of behavioral impulsivity and aggression tasks as endophenotypes for borderline personality disorder 
Journal of psychiatric research  2009;43(12):1036-1048.
Borderline personality disorder (BPD) is marked by aggression and impulsive, often self-destructive behavior. Despite the severe risks associated with BPD, relatively little is known about the disorder’s etiology. Identification of genetic correlates (endophenotypes) of BPD would improve the prospects of targeted interventions for more homogeneous subsets of borderline patients characterized by specific genetic vulnerabilities. The current study evaluated behavioral measures of aggression and impulsivity as potential endophenotypes for BPD. Subjects with BPD (N = 127), a non cluster B personality disorder (OPD N = 122), or healthy volunteers (HV N = 112) completed self report and behavioral measures of aggression, motor impulsivity and cognitive impulsivity. Results showed that BPD subjects demonstrated more aggression and motor impulsivity than HV (but not OPD) subjects on behavioral tasks. In contrast, BPD subjects self-reported more impulsivity and aggression than either comparison group. Subsequent analyses showed that among BPD subjects behavioral aggression was associated with self-reported aggression, while behavioral and self-report impulsivity measures were more modestly associated. Overall, the results provide partial support for the use of behavioral measures of aggression and motor impulsivity as endophenotypes for BPD, with stronger support for behavioral aggression measures as an endophenotype for aggression within BPD samples.
doi:10.1016/j.jpsychires.2009.01.002
PMCID: PMC2853811  PMID: 19232640
Borderline personality disorder; Endophenotype; Aggression; Impulsivity
21.  Repeat neurobehavioral study of borderline personality disorder. 
Previous research has tentatively identified a large subgroup of patients with borderline personality disorder (BPD) with histories of developmental or acquired brain insults. Similarly, these studies have demonstrated a possible biological correlation between the severity of BPD and the number of previous brain insults. The possibility of frontal system cognitive dysfunction in BPD has been raised. This single-blind, case-control study of BPD showed that 13 of 24 subjects with BPD had suffered a brain insult. Correlations between neurodevelopmental/acquired brain injury score and the diagnostic interview for borderline (DIB) score (r = 0.47), and between frontal system cognitive functioning and DIB score (r = -0.37) were seen. Neurocognitive testing and comparison with a cohort of subjects with traumatic brain injury (TBI) showed a pattern of similar cognitive functioning between the 2 groups, with the only differences on individual tests being in the direction of worse functioning in the group with BPD on 2 tasks. These results support the hypotheses described above. The main limitation reflects the low numbers of subjects.
PMCID: PMC1188729  PMID: 8580113
22.  Momentary emotion surrounding bulimic behaviors in women with bulimia nervosa and borderline personality disorder 
Journal of psychiatric research  2012;46(11):1492-1500.
Background
Bulimia nervosa (BN) and borderline personality disorder (BPD) are disorders that involve emotion dysregulation, for negative emotion in particular, as well as impulsive behaviors beyond binge eating and vomiting. Given these similarities in psychopathology, it is not surprising that those with BN also present with BPD in approximately one third of cases. Improved understanding of similarities and differences in the experience of negative and positive emotion could aid in the development of treatments specifically tailored to the needs of these disorders.
Methods
In this study, we examined Ecological Momentary Assessment (EMA) data from 133 women diagnosed with BN, 25 of whom also exhibited diagnostic levels of BPD. Emotions and behaviors were assessed daily, with multiple random and event-contingent signals to complete questionnaires on portable digital devices, for a period of two weeks.
Results
Results indicated that the BPD group experienced higher negative emotional variability on bulimic event days. Both groups also demonstrated increasing negative emotion and decreasing positive emotion pre-binge eating and vomiting, with levels of negative emotion decreasing and positive emotion increasing after, for both behaviors.
Conclusions
In terms of group differences, additive effects were found for the BN comorbid with BPD group, who demonstrated greater negative emotional variability, on bulimic event days, and also had higher overall levels of negative emotion pre- and post-binge eating. Those with BN only, however, displayed increasing trajectories of positive emotion before and after binge eating and after vomiting, indicating a potential emotional dampening effect of BPD.
doi:10.1016/j.jpsychires.2012.08.014
PMCID: PMC3635132  PMID: 22959165
borderline personality disorder; bulimia nervosa; binging; vomiting; emotion dysregulation
23.  Enhanced emotion-induced amnesia in borderline personality disorder 
Psychological medicine  2007;37(7):971-981.
Background
Current biological concepts of borderline personality disorder (BPD) emphasize the interference of emotional hyperarousal and cognitive functions. A prototypical example is episodic memory. Pre-clinical investigations of emotion–episodic memory interactions have shown specific retrograde and anterograde episodic memory changes in response to emotional stimuli. These changes are amygdala dependent and vary as a function of emotional arousal and valence.
Method
To determine whether there is amygdala hyper-responsiveness to emotional stimuli as the underlying pathological substrate of cognitive dysfunction in BPD, 16 unmedicated female patients with BPD were tested on the behavioural indices of emotion-induced amnesia and hypermnesia established in 16 healthy controls.
Results
BPD patients displayed enhanced retrograde and anterograde amnesia in response to presentation of negative stimuli, while positive stimuli elicited no episodic memory-modulating effects.
Conclusion
These findings suggest that an amygdala hyper-responsiveness to negative stimuli may serve as a crucial aetiological contributor to emotion-induced cognitive dysfunction in BPD.
doi:10.1017/S0033291706009792
PMCID: PMC2633116  PMID: 17224096
24.  Neurobehavioral study of borderline personality disorder. 
The existence of an "organic" subgroup of borderline personality disorder (BPD) has been postulated. This report is of a case-controlled, chart-review study of BPD. The control sample consisted of patients with a variety of psychiatric diagnoses. The study found that 81% of the patients with BPD and 22% of the control patients had a history of brain injury, either developmental (44%), acquired (58%) or both. Furthermore, there was a positive correlation between the summed number of developmental and acquired brain injuries and the score on the retro-Diagnostic Interview for Borderline. A pilot neuropsychological study showed that seven of nine subjects with BPD had evidence of frontal system dysfunction. These results help to support the hypothesized existence of an organic BPD subgroup.
PMCID: PMC1188508  PMID: 8499428
25.  Frontolimbic dysfunction in response to facial emotion in borderline personality disorder: an event-related fMRI study 
Psychiatry research  2007;155(3):231-243.
Clinical hallmarks of borderline personality disorder (BPD) include social and emotional dysregulation. We tested a model of frontolimbic dysfunction in facial emotion processing in BPD. Groups of 12 unmedicated adults with BPD by DSM-IV and 12 demographically-matched healthy controls (HC) viewed facial expressions (Conditions) of neutral emotion, fear and anger, and made gender discriminations during rapid event-related functional magnetic resonance imaging (fMRI). Analysis of variance of Region of Interest signal change revealed a statistically significant effect of the Group-by-Region-by-Condition interaction. This was due to the BPD group exhibiting a significantly larger magnitude of deactivation (relative to HC) in the bilateral rostral/subgenual anterior cingulate cortex (ACC) to fear and in the left ACC to fear minus neutral; and significantly greater activation in the right amygdala to fear minus neutral. There were no significant between-group differences in ROI signal change in response to anger. In voxel-wise analyses constrained within these ROIs, the BPD group exhibited significant changes in the fear minus neutral contrast, with relatively less activation in the bilateral rostral/subgenual ACC, and greater activation in the right amygdala. In the anger minus neutral contrast this pattern was reversed, with the BPD group showing greater activation in the bilateral rostral/subgenual ACC and less activation in the bilateral amygdala. We conclude that adults with BPD exhibit changes in fronto-limbic activity in the processing of fear stimuli, with exaggerated amygdala response and impaired emotion-modulation of ACC activity. The neural substrates underlying processing of anger may also be altered. These changes may represent an expression of the volumetric and serotonergic deficits observed in these brain areas in BPD.
doi:10.1016/j.pscychresns.2007.03.006
PMCID: PMC2084368  PMID: 17601709
anterior cingulate cortex; amygdala; fear; anger; functional magnetic resonance imaging

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