Social Judgement in Borderline Personality Disorder

Background

Borderline personality disorder (BPD) is a common and serious mental illness, associated with a high risk of suicide and self harm. Those with a diagnosis of BPD often display difficulties with social interaction and struggle to form and maintain interpersonal relationships. Here we investigated the ability of participants with BPD to make social inferences from faces.

Method

20 participants with BPD and 21 healthy controls were shown a series of faces and asked to judge these according to one of six characteristics (age, distinctiveness, attractiveness, intelligence, approachability, trustworthiness). The number and direction of errors made (compared to population norms) were recorded for analysis.

Results

Participants with a diagnosis of BPD displayed significant impairments in making judgements from faces. In particular, the BPD Group judged faces as less approachable and less trustworthy than controls. Furthermore, within the BPD Group there was a correlation between scores on the Childhood Trauma Questionnaire (CTQ) and bias towards judging faces as unapproachable.

Conclusion

Individuals with a diagnosis of BPD have difficulty making appropriate social judgements about others from their faces. Judging more faces as unapproachable and untrustworthy indicates that this group may have a heightened sensitivity to perceiving potential threat, and this should be considered in clinical management and treatment.     

Affective Disorders among Patients with Borderline Personality Disorder

Background

The high co-occurrence between borderline personality disorder and affective disorders has led many to believe that borderline personality disorder should be considered as part of an affective spectrum. The aim of the present study was to examine whether the prevalence of affective disorders are higher for patients with borderline personality disorder than for patients with other personality disorders.

Methods

In a national cross-sectional study of patients receiving mental health treatment in Norway (N = 36 773), we determined whether psychiatric outpatients with borderline personality disorder (N = 1 043) had a higher prevalence of affective disorder in general, and whether they had an increased prevalence of depression, bipolar disorder or dysthymia specifically. They were compared to patients with paranoid, schizoid, dissocial, histrionic, obsessive-compulsive, avoidant, dependent, or unspecified personality disorder, as well as an aggregated group of patients with personality disorders other than the borderline type (N = 2 636). Odds ratios were computed for the borderline personality disorder group comparing it to the mixed sample of other personality disorders. Diagnostic assessments were conducted in routine clinical practice.

Results

More subjects with borderline personality disorder suffered from unipolar than bipolar disorders. Nevertheless, borderline personality disorder had a lower rate of depression and dysthymia than several other personality disorder groups, whereas the rate of bipolar disorder tended to be higher. Odds ratios showed 34% lower risk for unipolar depression, 70% lower risk for dysthymia and 66% higher risk for bipolar disorder in patients with borderline personality disorder compared to the aggregated group of other personality disorders.

Conclusions

The results suggest that borderline personality disorder has a stronger association with affective disorders in the bipolar spectrum than disorders in the unipolar spectrum. This association may reflect an etiological relationship or diagnostic overlapping criteria.     

Hypersensitivity in Borderline Personality Disorder during Mindreading

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.     

Increased Prefrontal Cortical Thickness Is Associated with Enhanced Abilities to Regulate Emotions in PTSD-Free Women with Borderline Personality Disorder

Previous studies suggest that amygdala, insula and prefrontal cortex (PFC) disintegrity play a crucial role in the failure to adequately regulate emotions in Borderline Personality Disorder (BPD). However, prior results are confounded by the high rate of comorbidity with Posttraumatic Stress Disorder (PTSD), which itself has been associated with changes in frontolimbic circuitry. We thus scrutinized the link between PFC, amygdala, insula, and the ability to regulate emotions, contrasting 17 women with BPD without comorbid PTSD to 27 non-clinical control women and in addition to those with BPD and PTSD (n = 14). BPD women without PTSD, but not those with comorbid PTSD, had increased cortical thickness in the dorsolateral PFC (DLPFC) in comparison to control women. Furthermore, cortical thickness in the DLPFC of BPD women without PTSD positively correlated with emotion regulation scores and furthermore was positively associated with amygdala volume, as well as cortical thickness of the insula. Our findings highlight the importance of disentangling the impact of BPD and PTSD on the brain and suggest possible compensatory mechanisms for the impaired emotion regulation in BPD women without PTSD.     

Negative Emotion Regulation in Patients with Posttraumatic Stress Disorder

Objective

To explore the neural mechanisms of negative emotion regulation in patients with post-traumatic stress disorder (PTSD).

Methods

Twenty PTSD patients and 20 healthy subjects were recruited. Event-related functional magnetic resonance imaging (fMRI) was used to investigate the modification of emotional responses to negative stimuli. Participants were required to regulate their emotional reactions according to the auditory regulation instructions via headphones, to maintain, enhance or diminish responses to negative stimuli during fMRI scans.

Results

The PTSD group showed poorer modification performance than the control group when diminishing responses to negative stimuli. On fMRI, the PTSD group showed decreased activation in the inferior frontal cortex, inferior parietal lobule, insula and putamen, and increased activation in posterior cingulate cortex and amygdala during up-regulation of negative emotion. Similar decreased activation regions were found during down-regulation of negative emotion, but no increased activation was found.

Conclusion

Trauma exposure might impair the ability to down-regulate negative emotion. The present findings will improve our understanding of the neural mechanisms of emotion regulation underlying PTSD.     

Mesiotemporal Volume Loss Associated with Disorder Severity: A VBM Study in Borderline Personality Disorder

Results of MRI volumetry in Borderline Personality Disorder (BPD) are inconsistent. Some, but not all, studies reported decreased hippocampus, amygdala, and/or prefrontal volumes. In the current study, we used rater-independent voxel-based morphometry (VBM) in 33 female BPD patients and 33 healthy women. We measured gray matter (GM) volumes of the whole brain and of three volumes of interest (VOI), i.e., the hippocampus/parahippocampal gyrus, the amygdala and the anterior cingulate gyrus (ACC). Analyses were conducted using lifetime diagnoses of posttraumatic stress disorder (PTSD) and major depression (MD) as covariates. We used adversive childhood experiences and the numbers of BPD criteria (as an indicator of disorder severity) to investigate associations with GM volumes. We did not find volume differences between BPD patients and healthy subject, neither of the whole brain nor of the three VOIs, independent of presence or absence of comorbid PTSD and MD. We also did not find a relationship between childhood maltreatment and the patients’ brain volumes. However, within the patient group, the number of BPD criteria fulfilled was inversely correlated with left hippocampal/parahippocampal volume (x=-32, y=-23, z=-18, k=496, t=5.08, p=.007). Consequently, mesiotemporal GM volumes do not seem to differentiate patients from healthy subjects, but might be associated with symptom severity within the BPD group.     

Functional connectivity of pain-mediated affect regulation in Borderline Personality Disorder

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.     

Mapping Cortical Degeneration in ALS with Magnetization Transfer Ratio and Voxel-Based Morphometry

Pathological and imaging data indicate that amyotrophic lateral sclerosis (ALS) is a multisystem disease involving several cerebral cortical areas. Advanced quantitative magnetic resonance imaging (MRI) techniques enable to explore in vivo the volume and microstructure of the cerebral cortex in ALS. We studied with a combined voxel-based morphometry (VBM) and magnetization transfer (MT) imaging approach the capability of MRI to identify the cortical areas affected by neurodegeneration in ALS patients. Eighteen ALS patients and 18 age-matched healthy controls were examined on a 1.5T scanner using a high-resolution 3D T1 weighted spoiled gradient recalled sequence with and without MT saturation pulse. A voxel-based analysis (VBA) was adopted in order to automatically compute the regional atrophy and MT ratio (MTr) changes of the entire cerebral cortex. By using a multimodal image analysis MTr was adjusted for local gray matter (GM) atrophy to investigate if MTr changes can be independent of atrophy of the cerebral cortex. VBA revealed several clusters of combined GM atrophy and MTr decrease in motor-related areas and extra-motor frontotemporal cortex. The multimodal image analysis identified areas of isolated MTr decrease in premotor and extra-motor frontotemporal areas. VBM and MTr are capable to detect the distribution of neurodegenerative alterations in the cortical GM of ALS patients, supporting the hypothesis of a multi-systemic involvement in ALS. MT imaging changes exist beyond volume loss in frontotemporal cortices.     

Negative Evaluation Bias for Positive Self-Referential Information in Borderline Personality Disorder

Previous research has suggested that patients meeting criteria for borderline personality disorder (BPD) display altered self-related information processing. However, experimental studies on dysfunctional self-referential information processing in BPD are rare. In this study, BPD patients (N = 30) and healthy control participants (N = 30) judged positive, neutral, and negative words in terms of emotional valence. Referential processing was manipulated by a preceding self-referential pronoun, an other-referential pronoun, or no referential context. Subsequently, patients and participants completed a free recall and recognition task. BPD patients judged positive and neutral words as more negative than healthy control participants when the words had self-reference or no reference. In BPD patients, these biases were significantly correlated with self-reported attributional style, particularly for negative events, but unrelated to measures of depressive mood. However, BPD patients did not differ from healthy control participants in a subsequent free recall task and a recognition task. Our findings point to a negative evaluation bias for positive, self-referential information in BPD. This bias did not affect the storage of information in memory, but may be related to self-attributions of negative events in everyday life in BPD.     

Effects of Hormone Therapy on Brain Volumes Changes of Postmenopausal Women Revealed by Optimally-Discriminative Voxel-Based Morphometry

Backgrounds

The Women''s Health Initiative Memory Study Magnetic Resonance Imaging (WHIMS-MRI) provides an opportunity to evaluate how menopausal hormone therapy (HT) affects the structure of older women’s brains. Our earlier work based on region of interest (ROI) analysis demonstrated potential structural changes underlying adverse effects of HT on cognition. However, the ROI-based analysis is limited in statistical power and precision, and cannot provide fine-grained mapping of whole-brain changes.

Methods

We aimed to identify local structural differences between HT and placebo groups from WHIMS-MRI in a whole-brain refined level, by using a novel method, named Optimally-Discriminative Voxel-Based Analysis (ODVBA). ODVBA is a recently proposed imaging pattern analysis approach for group comparisons utilizing a spatially adaptive analysis scheme to accurately locate areas of group differences, thereby providing superior sensitivity and specificity to detect the structural brain changes over conventional methods.

Results

Women assigned to HT treatments had significant Gray Matter (GM) losses compared to the placebo groups in the anterior cingulate and the adjacent medial frontal gyrus, and the orbitofrontal cortex, which persisted after multiple comparison corrections. There were no regions where HT was significantly associated with larger volumes compared to placebo, although a trend of marginal significance was found in the posterior cingulate cortical area. The CEE-Alone and CEE+MPA groups, although compared with different placebo controls, demonstrated similar effects according to the spatial patterns of structural changes.

Conclusions

HT had adverse effects on GM volumes and risk for cognitive impairment and dementia in older women. These findings advanced our understanding of the neurobiological underpinnings of HT effects.     

Comparing Screening Instruments to Predict Posttraumatic Stress Disorder

Background

Following traumatic exposure, a proportion of trauma victims develops posttraumatic stress disorder (PTSD). Early PTSD risk screening requires sensitive instruments to identify everyone at risk for developing PTSD in need of diagnostic follow-up.

Aims

This study compares the accuracy of the 4-item SPAN, 10-item Trauma Screening Questionnaire (TSQ) and 22-item Impact of Event Scale-Revised (IES-R) in predicting chronic PTSD at a minimum sensitivity of 80%.

Method

Injury patients admitted to a level-I trauma centre (N = 311) completed the instruments at a median of 23 days and were clinically assessed for PTSD at 6 months. Areas under the curve and specificities at 80% sensitivity were compared between instruments.

Results

Areas under the curve in all instruments were adequate (SPAN: 0.83; TSQ: 0.82; IES-R: 0.83) with no significant differences. At 80% sensitivity, specificities were 64% for SPAN, 59% for TSQ and 72% for IES-R.

Conclusion

The SPAN, TSQ and IES-R show similar accuracy in early detection of individuals at risk for PTSD, despite differences in number of items. The modest specificities and low positive predictive values found for all instruments could lead to relatively many false positive cases, when applied in clinical practice.     

Structural MRI in Frontotemporal Dementia: Comparisons between Hippocampal Volumetry,Tensor-Based Morphometry and Voxel-Based Morphometry

Background

MRI is an important clinical tool for diagnosing dementia-like diseases such as Frontemporal Dementia (FTD). However there is a need to develop more accurate and standardized MRI analysis methods.

Objective

To compare FTD with Alzheimer’s Disease (AD) and Mild Cognitive Impairment (MCI) with three automatic MRI analysis methods - Hippocampal Volumetry (HV), Tensor-based Morphometry (TBM) and Voxel-based Morphometry (VBM), in specific regions of interest in order to determine the highest classification accuracy.

Methods

Thirty-seven patients with FTD, 46 patients with AD, 26 control subjects, 16 patients with progressive MCI (PMCI) and 48 patients with stable MCI (SMCI) were examined with HV, TBM for shape change, and VBM for gray matter density. We calculated the Correct Classification Rate (CCR), sensitivity (SS) and specificity (SP) between the study groups.

Results

We found unequivocal results differentiating controls from FTD with HV (hippocampus left side) (CCR = 0.83; SS = 0.84; SP = 0.80), with TBM (hippocampus and amygdala (CCR = 0.80/SS = 0.71/SP = 0.94), and with VBM (all the regions studied, especially in lateral ventricle frontal horn, central part and occipital horn) (CCR = 0.87/SS = 0.81/SP = 0.96). VBM achieved the highest accuracy in differentiating AD and FTD (CCR = 0.72/SS = 0.67/SP = 0.76), particularly in lateral ventricle (frontal horn, central part and occipital horn) (CCR = 0.73), whereas TBM in superior frontal gyrus also achieved a high accuracy (CCR = 0.71/SS = 0.68/SP = 0.73). TBM resulted in low accuracy (CCR = 0.62) in the differentiation of AD from FTD using all regions of interest, with similar results for HV (CCR = 0.55).

Conclusion

Hippocampal atrophy is present not only in AD but also in FTD. Of the methods used, VBM achieved the highest accuracy in its ability to differentiate between FTD and AD.     

Aberrant Methylation of Gene Associated CpG Sites Occurs in Borderline Personality Disorder

Borderline personality disorder (BPD) is a complex psychiatric disease with an increased impact in the last years. While the diagnosis and therapy are well established, little is known on the pathogenesis of borderline personality disorder. Previously, a significant increase in DNA methylation of relevant neuropsychiatric genes in BPD patients has been reported. In our study we performed genome wide methylation analysis and revealed specific CpG sites that exhibited increased methylation in 24 female BPD patients compared to 11 female healthy controls. Bead chip technology and quantitative bisulfite pyrosequencing showed a significantly increased methylation at CpG sites of APBA2 (1.1 fold) and APBA3 (1.1 fold), KCNQ1 (1.5 fold), MCF2 (1.1 fold) and NINJ2 (1.2 fold) in BPD patients. For the CpG sites of GATA4 and HLCS an increase in DNA methylation was observed, but was only significant in the bead chip assay. Moreover genome wide methylation levels of blood samples of BPD patients and control samples are similar. In summary, our results show a significant 1.26 fold average increase in methylation at the analyzed gene associated CpG sites in the blood of BPD patients compared to controls samples (p<0.001). This data may provide new insights into epigenetic mechanisms underlying the pathogenesis of BPD.     

创伤后应激障碍对慢性不可预见性应激抑郁模型的影响

目的:观察创伤后应激障碍(PTSD)对慢性不可预见性应激(CUS)抑郁模型的影响。方法:采用足底电击的方法建立大鼠创伤后应激障碍模型。成年雄性S-D大鼠40只随机分为四组(n=10):对照组(C组)、PTSD组、CUS组、PTSD+CUS组(P+C组)。在1、7、14、21天测量大鼠体重,并行糖水偏好和强迫游泳实验,在7、14、21天做条件性恐惧实验。结果:与C组相比,CUS组和P+C组体重增加缓慢,PTSD组体重正常。CUS组于第21天出现糖水消耗比例降低,强迫游泳不动时间增加。P+C组于第14天即出现上述抑郁表现。条件性恐惧实验中,PTSD组与PTSD+CUS组僵直时间显著增加,CUS组无明显变化。结论:创伤后应激障碍的动物更易产生抑郁表现。     

Posttraumatic Stress Disorder Increases Sensitivity to Long Term Losses among Patients with Major Depressive Disorder

Background

Decisions under risk and with outcomes that are delayed in time are ubiquitous in real life and can have a significant impact on the health and wealth of the decision-maker. Despite its potential relevance for real-world choices, the degree of aberrant risky and intertemporal decision-making in patients suffering from major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) has received little attention to date.

Method

We used a case-control design to compare decision-making in healthy control subjects (N=16) versus untreated depressed subjects in a current major depressive episode (N=20). In order to examine how major depressive disorder (MDD) may impact decision-making, subjects made decisions over (1) risky outcomes and (2) delayed outcomes in the domain of gains and losses using choice paradigms from neuroeconomics. In a pre-planned analysis, depressed subjects were subdivided into those with primary PTSD along with comorbid MDD (MDD+PTSD) versus those with primary MDD without PTSD (MDD-only). Choice behavior was modeled via a standard econometric model of intertemporal choice, a quasi-hyperbolic temporal discounting function, which was estimated for each subject group separately.

Results

Under conditions of potential gain, depressed subjects demonstrated greater discounting for gains across all time frames compared to controls. In the realm of losses, both subgroups of depressed subjects discounted more steeply than controls for short time frames. However, for delayed losses ranging from >1-10 years, MDD+PTSD subjects showed shallower discounting rates relative to MDD-only subjects, who continued to discount future losses steeply. Risk attitudes did not contribute to differences in intertemporal choice.

Conclusions

Depressed patients make choices that minimize current pain and maximize current reward, despite severe later consequences or lost opportunities. Anxiety associated with PTSD may serve as a partially protective factor in decision-making about long-term potential losses compared to MDD patients without PTSD.     

Posttraumatic Stress Disorder Disturbs Coronary Tone and Its Regulatory Mechanisms

Posttraumatic stress disorder (PTSD) is associated with myocardial injury, but changes in coronary regulatory mechanisms in PTSD have not been investigated. This study evaluated the effect of PTSD-inducing stress on coronary tone and its regulation by nitric oxide (NO) and voltage-gated K⁺ channels. PTSD was induced by exposing rats to predator stress, 15 min daily for 10 days, followed by 14 stress-free days. Presence of PTSD was confirmed by the elevated plus-maze test. Coronary tone was evaluated from changes in coronary perfusion pressure of Langendorff isolated hearts. Predator stress induced significant decreases in coronary tone of isolated hearts and in blood pressure of intact rats. L-NAME, a non-selective NO synthase (NOS) inhibitor, but not S-MT, a selective iNOS inhibitor, and increased coronary tone of control rats. In PTSD rats, both L-NAME and S-MT increased coronary tone. Therefore, the stress-induced coronary vasodilation resulted from NO overproduction by both iNOS and eNOS. NOS induction was apparently due to systemic inflammation as evidenced by increased serum interleukin-1β and C-reactive protein in PTSD rats. Decreased corticosterone in PTSD rats may have contributed to inflammation and its effect on coronary tone. PTSD was also associated with voltage-gated K⁺ channel dysfunction, which would have also reduced coronary tone.     

Early Affective Processing in Patients with Acute Posttraumatic Stress Disorder: Magnetoencephalographic Correlates

Background

In chronic PTSD, a preattentive neural alarm system responds rapidly to emotional information, leading to increased prefrontal cortex (PFC) activation at early processing stages (<100 ms). Enhanced PFC responses are followed by a reduction in occipito-temporal activity during later processing stages. However, it remains unknown if this neuronal pattern is a result of a long lasting mental disorder or if it represents changes in brain function as direct consequences of severe trauma.

Methodology

The present study investigates early fear network activity in acutely traumatized patients with PTSD. It focuses on the question whether dysfunctions previously observed in chronic PTSD patients are already present shortly after trauma exposure. We recorded neuromagnetic activity towards emotional pictures in seven acutely traumatized PTSD patients between one and seven weeks after trauma exposure and compared brain responses to a balanced healthy control sample. Inverse modelling served for mapping sources of differential activation in the brain.

Principal Findings

Compared to the control group, acutely traumatized PTSD patients showed an enhanced PFC response to high-arousing pictures between 60 to 80 ms. This rapid prefrontal hypervigilance towards arousing pictorial stimuli was sustained during 120–300 ms, where it was accompanied by a reduced affective modulation of occipito-temporal neural processing.

Conclusions

Our findings indicate that the hypervigilance-avoidance pattern seen in chronic PTSD is not necessarily a product of an endured mental disorder, but arises as an almost immediate result of severe traumatisation. Thus, traumatic experiences can influence emotion processing strongly, leading to long-lasting changes in trauma network activation and expediting a chronic manifestation of maladaptive cognitive and behavioral symptoms.     

A Systematic Review of Economic Evaluations of Treatments for Borderline Personality Disorder

Purpose

The borderline personality disorder is a common mental disorder. It is frequently associated with various mental co-morbidities and a fundamental loss of functioning. The borderline personality disorder causes high costs to society. The aim of this study was to perform a systematic literature review of existing economic evaluations of treatments for borderline personality disorder.

Materials and Methods

We performed a systematic literature search in MEDLINE, EMBASE, PsycINFO and NHSEED for partial and full economic evaluations regarding borderline personality disorder. Reported cost data were inflated to the year 2012 and converted into US-$ using purchasing power parities to allow for comparability. Quality assessment of the studies was performed by means of the Consensus on Health Economic Criteria checklist, a checklist developed by a Delphi method in cooperation with 23 international experts.

Results

We identified 6 partial and 9 full economic evaluations. The methodical quality was moderate (fulfilled quality criteria: 79.2% [SD: 15.4%] in partial economic evaluations, 77.3% [SD: 8.5%] in full economic evaluations). Most evaluations analysed psychotherapeutic interventions. Although ambiguous, most evidence exists on dialectical-behavioural therapy. Cognitive behavioural therapy and schema-focused therapy are cost-saving. Evidence on other interventions is scarce.

Conclusion

The economic evidence is not sufficient to draw robust conclusions for all treatments. It is possible that some treatments are cost-effective. Most evidence exists on dialectical-behavioural therapy. Yet, it is ambiguous. Further research concerning the cost-effectiveness of treatments is necessary as well as the identification of relevant cost categories and the validation of effect measures.