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.

Intact Classical Fear Conditioning to Interpersonally Threatening Stimuli in Borderline Personality Disorder.

Threat hypersensitivity is regarded as a central mechanism of deficient emotion regulation, a core feature of patients with borderline personality disorder (BPD). Here, we employed a classical fear-conditioning protocol in which interpersonally threatening, interpersonally non-threatening, and non-social (neutral) visual stimuli were predictive of an aversive auditory stimulus in a sample of 23 medication-free adult female patients with BPD and 21 age- and IQ-matched healthy women. The results did not confirm the hypothesized enhanced and prolonged conditioned skin conductance responses (SCR) and subjective stress and expectancy ratings to interpersonally threatening stimuli in patients with BPD compared to healthy women. Patients with BPD generally expected the aversive stimulus more often irrespective of stimulus category and conditioning. Furthermore, patients with BPD showed larger conditioned SCR to interpersonally non-threatening and neutral than interpersonally threatening stimuli, while interpersonally threatening stimuli elicited higher SCR compared to non-threatening or neutral stimuli in healthy controls. Together with previous studies, the results suggest no alterations in fear conditioning to generally aversive stimuli in BPD. Further studies using stimuli with BPD-specific topics, such as abandonment or rejection, and/or to investigate more interpersonal forms of learning, such as observational or instructed conditioning, are urgently needed to further elucidate the mechanisms involved in the etiology and maintenance of threat hypersensitivity in BPD.

Individualized treatment response prediction of dialectical behavior therapy for borderline personality disorder using multimodal magnetic resonance imaging.

INTRODUCTION: Individualized treatment prediction is crucial for the development and selection of personalized psychiatric interventions. Here, we use random forest classification via pretreatment clinical and demographical (CD), functional, and structural magnetic resonance imaging (MRI) data from patients with borderline personality disorder (BPD) to predict individual treatment response. METHODS: Before dialectical behavior therapy (DBT), 31 female patients underwent functional (three different emotion regulation tasks) and structural MRI. DBT response was predicted using CD and MRI data in previously identified anatomical regions, which have been reported to be multimodally affected in BPD. RESULTS: Amygdala and parahippocampus activation during a cognitive reappraisal task (in contrasts displaying neural activation for emotional challenge and for regulation), along with severity measures of BPD psychopathology and gray matter volume of the amygdala, provided best predictive power with neuronal hyperractivities in nonresponders. All models, except one model using CD data solely, achieved significantly better accuracy (>70.25%) than a simple all-respond model, with sensitivity and specificity of >0.7 and >0.7, as well as positive and negative likelihood ratios of >2.74 and <0.36 each. Surprisingly, a model combining all data modalities only reached rank five of seven. Among the functional tasks, only the activation elicited by a cognitive reappraisal paradigm yielded sufficient predictive power to enter the final models. CONCLUSION: This proof of principle study shows that it is possible to achieve good predictions of psychotherapy outcome to find the most valid predictors among numerous variables via using a random forest classification approach.

Effects of a Painful Stimulus on Stress Regulation in Male Patients With Borderline Personality Disorder: A Pilot Study.

Pain processing in relation to stress has so far not been investigated in male patients with borderline personality disorder (BPD). This experimental pilot study examined 17 male BPD patients and 20 male healthy controls (HCs) to assess the effects of a pain stimulus on arousal, aggression, pain (ratings), and heart rate. At baseline, BPD patients showed significantly higher arousal and aggression; however, there was no significant difference in heart rate compared to the HC group. Following stress induction, a noninvasive mechanical pain stimulus was applied. No significant differences in pain ratings or heart rates were found between the groups. For arousal, a significantly stronger decrease was revealed in the BPD group compared to the HC group (t = 2.16, p = .038). Concerning aggression, the BPD group showed a significantly greater decrease after the pain stimulus than the HC group (t = 3.25, p = .002). This data showed that nonsuicidal self-injury can reduce arousal and aggression in male BPD.

Correlates of Aggression in Personality Disorders: an Update.

PURPOSE OF REVIEW: This review article aims at giving an update on studies investigating correlates of aggression in personality disorders during the last 5 years. RECENT FINDINGS: Most data refer to borderline personality disorder (BPD) and antisocial personality disorder (ASPD). In BPD, emotion dysregulation, hypersensitivity to interpersonal rejection/threat, increased rumination, increased negative urgency, aggression-related knowledge structures, and invalidation were either corroborated or emerged as psychological correlates of aggression, while reduced ambiguity sensitivity, hyposensitivity to interpersonal threat, and reduced mindfulness were associated with aggression in ASPD. Neurobiologically, alterations of the monoaminooxidase-A-, the oxytocinergic-, and the prefrontal-limbic-system as well as increases of the thyroid hormone T3, γ-aminobutyric acid and several inflammatory markers were associated with increased aggression across various personality disorders. Our understanding of correlates of aggression in personality disorders has increased over the last 5 years. More efforts in improving the conceptualization of personality disorders and aggression are needed to develop innovative treatments for those affected.

Assessing the marks of change: how psychotherapy alters the brain structure in women with borderline personality disorder.

BACKGROUND: There is increasing evidence that psychotherapy can alter the function of the brain of patients with borderline personality disorder (BPD). However, it is not known whether psychotherapy can also modify the brain structure of patients with BPD. METHODS: We used structural MRI data of female patients with BPD before and after participation in 12 weeks of residential dialectical behavioural therapy (DBT) and compared them to data from female patients with BPD who received treatment as usual (TAU). We applied voxel-based morphometry to study voxel-wise changes in grey matter volume over time. RESULTS: We included 31 patients in the DBT group and 17 in the TAU group. Patients receiving DBT showed an increase of grey matter volume in the anterior cingulate cortex, inferior frontal gyrus and superior temporal gyrus together with an alteration of grey matter volume in the angular gyrus and supramarginal gyrus compared with patients receiving TAU. Furthermore, therapy response correlated with increase of grey matter volume in the angular gyrus. LIMITATIONS: Only women were investigated, and groups differed in size, medication (controlled for) and intensity of the treatment condition. CONCLUSION: We found that DBT increased grey matter volume of brain regions that are critically implicated in emotion regulation and higher-order functions, such as mentalizing. The role of the angular gyrus for treatment response may reside in its cross-modal integrative function. These findings enhance our understanding of psychotherapy mechanisms of change and may foster the development of neurobiologically informed therapeutic interventions.

Amygdala structure and aggressiveness in borderline personality disorder.

Aggressiveness is considered an important clinical feature of borderline personality disorder (BPD) and has been associated with alterations of the amygdala. However, studies that analyzed the exact location of amygdala alterations associated with aggressiveness in BPD or that systematically compared female and male BPD patients are missing. In the current study, we therefore investigated a sex-mixed sample of BPD patients and healthy volunteers and applied an automated segmentation method that allows the study of both, alterations of amygdala volume and localized amygdala shape. Volumetric results revealed no difference in amygdala volume between BPD patients and healthy volunteers, but a trend for a positive association between volume of the right amygdala and aggressiveness in male BPD patients. Analyses of amygdala shape showed a trend for a group by sex interaction effect in the left laterobasal amygdala, without a difference in subgroup analyses. Finally, regions of the left superficial and laterobasal amygdala of male BPD patients were positively associated with aggressiveness. In sum, our results emphasize the need to consider sex-specific effects and demonstrate a link between male BPD patients' aggressiveness and amygdala regions that are particularly related to social information processing and associative emotional learning.

Assessing the marks of change: how psychotherapy alters the brain structure in women with borderline personality disorder.

BACKGROUND: There is increasing evidence that psychotherapy can alter the function of the brain of patients with borderline personality disorder (BPD). However, it is not known whether psychotherapy can also modify the brain structure of patients with BPD. METHODS: We used structural MRI data of female patients with BPD before and after participation in 12 weeks of residential dialectical behavioural therapy (DBT) and compared them to data from female patients with BPD who received treatment as usual (TAU). We applied voxel-based morphometry to study voxel-wise changes in grey matter volume over time. RESULTS: We included 31 patients in the DBT group and 17 in the TAU group. Patients receiving DBT showed an increase of grey matter volume in the anterior cingulate cortex, inferior frontal gyrus and superior temporal gyrus together with an alteration of grey matter volume in the angular gyrus and supramarginal gyrus compared with patients receiving TAU. Furthermore, therapy response correlated with increase of grey matter volume in the angular gyrus. LIMITATIONS: Only women were investigated, and groups differed in size, medication (controlled for) and intensity of the treatment condition. CONCLUSION: We found that DBT increased grey matter volume of brain regions that are critically implicated in emotion regulation and higher-order functions, such as mentalizing. The role of the angular gyrus for treatment response may reside in its cross-modal integrative function. These findings enhance our understanding of psychotherapy mechanisms of change and may foster the development of neurobiologically informed therapeutic interventions.

Brain Mechanisms Underlying Reactive Aggression in Borderline Personality Disorder-Sex Matters.

BACKGROUND: Aggression in borderline personality disorder (BPD) is thought to be mediated through emotion dysregulation via high trait anger. Until now, data comparing anger and aggression in female and male patients with BPD have been widely missing on the behavioral and particularly the brain levels. METHODS: Thirty-three female and 23 male patients with BPD and 30 healthy women and 26 healthy men participated in this functional magnetic resonance imaging study. We used a script-driven imagery task consisting of narratives of both interpersonal rejection and directing physical aggression toward others. RESULTS: While imagining both interpersonal rejection and acting out aggressively, a sex × group interaction was found in which male BPD patients revealed higher activity in the left amygdala than female patients. In the aggression phase, men with BPD exhibited higher activity in the lateral orbitofrontal and dorsolateral prefrontal cortices compared with healthy men and female patients. Positive connectivity between amygdala and posterior middle cingulate cortex was found in female patients but negative connectivity was found in male patients with BPD. Negative modulatory effects of trait anger on amygdala-dorsolateral prefrontal cortex and amygdala-lateral orbitofrontal cortex coupling were shown in male BPD patients, while in female patients trait anger positively modulated dorsolateral prefrontal cortex-amygdala coupling. Trait aggression was found to positively modulate connectivity of the left amygdala to the posterior thalamus in male but not female patients. CONCLUSIONS: Data suggest poor top-down adjustment of behavior in male patients with BPD despite their efforts at control. Female patients appear to be less aroused through rejection and to successfully dampen aggressive tension during the imagination of aggressive behavior.

Emotion Dysregulation and Trait Anger Sequentially Mediate the Association Between Borderline Personality Disorder and Aggression.

Emotion dysregulation and trait anger are seen as central aspects of aggression in borderline personality disorder (BPD); their interplay in aggression of BPD, however, remains unclear. Using a cross-sectional design, we conducted a mediation analysis in a well-characterized sample of female and male BPD patients (n = 95). We found that emotion dysregulation and trait anger sequentially mediate the association between BPD and aggression. In accordance with major theories of BPD, emotion dysregulation may thus constitute an underlying factor that gives rise to anger and in turn to aggression in BPD. These findings may help to develop mechanism-based anti-aggressive interventions for patients with BPD, which should target emotion dysregulation and anger proneness.

The role of seeing blood in non-suicidal self-injury in female patients with borderline personality disorder.

Patients with Borderline Personality Disorder (BPD) often engage in non-suicidal self-injury (NSSI), to reduce arousal levels under stress. However, the importance of seeing blood for the effect of NSSI is yet unknown. The present pilot study examined 20 female BPD patients and 20 healthy controls (HC) to assess the role of seeing blood on arousal, pain, urge for NSSI (ratings) and heart rate (continuously measured). Participants completed two sessions consisting of stress induction (forced mental arithmetics with white noise), followed by a seven second non-invasive pain stimulus with a blade to the volar forearm. At one session, only the painful blade stimulus was applied, at the other, artificial blood was added. For arousal, a significantly stronger decrease was revealed in the BPD than in the HC group, however with no significant effects between blood and non-blood conditions. Concerning urge for NSSI, the BPD showed a significantly greater decrease in blood condition over time than the HC group. Interestingly, heart rate decreased stronger over time in the HC group during the blood condition than in BPD. For tension relief by non-damaging mechanical painful stimulus the addition of visible blood showed neither subjective (arousal, urge for NSSI), nor objective (heart rate) advantages.

Psychiatric comorbidities in a young man with subacute myelopathy induced by abusive nitrous oxide consumption: a case report.

Nitrous oxide (N2O), a long-standing anesthetic, is known for its recreational use, and its consumption is on the rise. Several case studies have reported neurological and psychiatric complications of N2O use. To date, however, there has not been a study using standardized diagnostic procedures to assess psychiatric comorbidities in a patient consuming N2O. Here, we report about a 35-year-old male with magnetic resonance imaging confirmed subacute myelopathy induced by N2O consumption, who suffered from comorbid cannabinoid and nicotine dependence as well as abuse of amphetamines, cocaine, lysergic acid diethylamide, and ketamine. Additionally, there was evidence of a preceding transient psychotic and depressive episode induced by synthetic cannabinoid abuse. In summary, this case raises awareness of an important mechanism of neural toxicity, with which physicians working in the field of substance-related disorders should be familiar. In fact, excluding N2O toxicity in patients with recognized substance-related disorders and new neurological deficits is compulsory, as untreated for months the damage to the nervous system is at risk of becoming irreversible.

Time course of facial emotion processing in women with borderline personality disorder: an ERP study.

BACKGROUND: Borderline personality disorder (BPD) is characterized by a negative perception of others. Previous studies have revealed deficits and biases in facial emotion recognition. This study investigates the behavioural and electrophysiological correlates underlying facial emotion processing in individuals with BPD. METHODS: The present study was conducted between July 2012 and May 2014. In an emotion classification task, unmedicated female patients with BPD as well as healthy women had to classify faces displaying blends of anger and happiness while the electroencephalogram was recorded. We analyzed visual event-related potentials (ERPs) reflecting early (P100), structural (N170) and categorical (P300) facial processing in addition to behavioural responses. RESULTS: We included 36 women with BPD and 29 controls in our analysis. Patients with BPD were more likely than controls to classify predominantly happy faces as angry. Independent of facial emotion, women with BPD showed enhanced early occipital P100 amplitudes. Additionally, temporo-occipital N170 amplitudes were reduced at right hemispherical electrode sites. Centroparietal P300 amplitudes were reduced particularly for predominantly happy faces and increased for highly angry faces in women with BPD, whereas in healthy volunteers this component was modulated by both angry and happy facial affect. LIMITATIONS: Our sample included only women, and no clinical control group was investigated. CONCLUSION: Our findings suggest reduced thresholds for facial anger and deficits in the discrimination of facial happiness in individuals with BPD. This biased perception is associated with alterations in very early visual as well as deficient structural and categorical processing of faces. The current data could help to explain the negative perception of others that may be related to the patients' impairments in interpersonal functioning.

Gender differences in aggression of borderline personality disorder.

Aggression is a core feature of borderline personality disorder (BPD). Well-replicated results from the general population indicate that men engage in aggression more frequently than women. This article addresses the question of whether gender also influences aggression in BPD, and whether the neurobiological mechanisms underlying aggressive behavior differ between male and female BPD patients. Data show that most self-reports, interviews and behavioral tasks investigating samples of BPD patients do not find enhanced aggressiveness in male patients, suggesting that BPD attenuates rather than aggravates gender differences usually present in the general population. Neurobiological studies comparing BPD patients with gender-matched healthy controls, however, reveal a number of interesting gender differences: On the one hand, there are well-replicated findings of reduced amygdala and hippocampal gray matter volumes in female BPD patients, while these findings are not shared by male patients with BPD. On the other hand, only male BPD patients exhibit reduced gray matter volume of the anterior cingulate cortex, increased gray matter volume of the putamen, reduced striatal activity during an aggression task, and a more pronounced deficit in central serotonergic responsivity. These neurobiological findings point to a particular importance of impulsivity for the aggression of male BPD patients. Limitations include the need to control for confounding influences of comorbidities, particularly as male BPD patients have been consistently found to show higher percentages of aggression-predisposing comorbid disorders, such as antisocial personality disorder, than female BPD patients. In the future, studies which include systematic comparisons between females and males are warranted in order to disentangle gender differences in aggression of BPD patients with the aim of establishing gender-sensitive treatments where needed.

Aggression in borderline personality disorder: A multidimensional model.

This article proposes a multidimensional model of aggression in borderline personality disorder (BPD) from the perspective of the biobehavioral dimensions of affective dysregulation, impulsivity, threat hypersensitivity, and empathic functioning. It summarizes data from studies that investigated these biobehavioral dimensions using self-reports, behavioral tasks, neuroimaging, neurochemistry as well as psychophysiology, and identifies the following alterations: (a) affective dysregulation associated with prefrontal-limbic imbalance, enhanced heart rate reactivity, skin conductance, and startle response; (b) impulsivity also associated with prefrontal-limbic imbalance, central serotonergic dysfunction, more electroencephalographic slow wave activity, and reduced P300 amplitude in a 2-tone discrimination task; (c) threat hypersensitivity associated with enhanced perception of anger in ambiguous facial expressions, greater speed and number of reflexive eye movements to angry eyes (shown to be compensated by exogenous oxytocin), enhanced P100 amplitude in response to blends of happy versus angry facial expressions, and prefrontal-limbic imbalance; (d) reduced cognitive empathy associated with reduced activity in the superior temporal sulcus/gyrus and preliminary findings of lower oxytocinergic and higher vasopressinergic activity; and (e) reduced self-other differentiation associated with greater emotional simulation and hyperactivation of the somatosensory cortex. These biobehavioral dimensions can be nicely linked to conceptual terms of the alternative Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) model of BPD, and thus to a multidimensional rather than a traditional categorical approach.

Deficits in pain perception in borderline personality disorder: results from the thermal grill illusion.

It is well documented that borderline personality disorder (BPD) is characterized by reduced pain sensitivity, which might be related to nonsuicidal self-injury and dissociative experiences in patients with BPD. However, it remains an open question whether this insensitivity relies at least partly on altered sensory integration or on an altered evaluation of pain or a combination of both. In this study, we used the thermal grill illusion (TGI), describing a painful sensation induced by the application of alternating cold and warm nonnoxious stimuli, in patients with either current or remitted BPD as well as matched healthy controls. Two additional conditions, applying warm or cold temperatures only, served as control. We further assessed thermal perception, discrimination, and pain thresholds. We found significantly reduced heat and cold pain thresholds for the current BPD group, as well as reduced cold pain thresholds for the remitted BPD group, as compared with the HC group. Current BPD patients perceived a less-intense TGI in terms of induced pain and unpleasantness, while their general ability to perceive this kind of illusion seemed to be unaffected. Thermal grill illusion magnitude was negatively correlated with dissociation and traumatization only in the current BPD patients. These results indicate that higher-order pain perception is altered in current BPD, which seems to normalize after remission. We discuss these findings against the background of neurophysiological evidence for the TGI in general and reduced pain sensitivity in BPD and suggest a relationship to alterations in N-methyl-D-aspartate neurotransmission.

Social dysfunctioning and brain in borderline personality disorder.

Interpersonal dysfunction is the most prominent and best discriminating characteristic in individuals with borderline personality disorder (BPD). Data from experimental psychopathology point to emotional lability, (auto-)aggression, threat hypersensitivity, poor chance of interpersonal repair, frequent misunderstandings and self/other diffusion as the most significant factors which contribute to the interpersonal derailments typical of BPD. Neuroscientific methods are suitable to elucidate the mechanisms which mediate deficient social functioning in BPD, i.e. affective dysregulation, impulsivity/disinhibition and poor social cognition as well as their neurobiological correlates. Low prefrontoamygdalar coupling together with low activity in inhibiting prefrontal areas, high activity in the mirror neuron system, low activity in the mentalizing circuit, and low anterior insular activity in case of social norm violations are the most significant functional neuroimaging findings that have been reported from individuals with BPD, up to now. In addition, peculiarities of facial emotion processing have been detected by means of psychophysiological methodology in BPD patients. Data have led to preliminary models of social dysfunctioning in BPD that have to be experimentally tested in the future, evolving neuroscience into an important tool to better understand what distresses patients with BPD when communicating with others.