Daniel Vega

Association between methylation of the glucocorticoid receptor gene, childhood maltreatment, and clinical severity in borderline personality disorder.

The hypothalamus-pituitary-adrenal axis (HPA) is essential in the regulation of stress responses. Increased methylation of the promoter region of the glucocorticoid receptor gene (NR3C1) has been described both in subjects with history of childhood trauma and in patients with Borderline Personality Disorder (BPD). However, no data on the possible association between a higher methylation of this gene and clinical severity is available. The aim of this study was to evaluate the association between NR3C1 methylation status, the history of childhood trauma, and current clinical severity in subjects with BPD. A sample of 281 subjects with BPD (diagnosed by SCID-II and DIB-R semi-structured diagnostic interviews) was recruited. Clinical variables included previous hospitalizations, self-injurious behavior, and self-reported history of childhood trauma. DNA was extracted from peripheral blood. The results indicated a significant positive correlation between NR3C1 methylation status and childhood maltreatment (specifically physical abuse). In addition, a positive correlation between methylation status and clinical severity (DIB-R total score and hospitalizations) was observed. These findings suggest that NR3C1 methylation in subjects with BPD may be associated not only with childhood trauma but also with clinical severity, adding new evidence to the involvement of gene-environment interactions in this disorder.

Validation of the Spanish version of the borderline symptom list, short form (BSL-23)

BackgroundThe Borderline Symptom List-23 (BSL-23) is a reliable and valid self-report instrument for assessing Borderline Personality Disorder (BPD) severity. The psychometric properties of the original version have proven to be adequate. The aim of the present study was to validate the Spanish language version of the BSL-23.MethodsThe BSL-23 was administered to 240 subjects with BPD diagnosis. Factor structure, reliability, test-retest stability, convergent validity, and sensitivity to change were analyzed.ResultsThe Spanish version of the BSL-23 replicates the one-factor structure of the original version. The scale has high reliability (Cronbach’s alpha=.949), as well as good test-retest stability, which was checked in a subsample (n=74; r=.734; p<.01). The Spanish BSL-23 shows moderate to high correlations with depressive symptomatology, state and trait anxiety, hostility and impulsivity scores and BPD measures. The Spanish BSL-23 is able to discriminate among different levels of BPD severity and shows satisfactory sensitivity to change after treatment, which was verified by assessing change before and after 12 group sessions of Dialectical Behavioral Therapy in a subgroup of 31 subjects.ConclusionsSimilar to the original BSL-23, the Spanish BSL-23 is a reliable and valid instrument for assessing BPD severity and sensitivity to change.

Converging Medial Frontal Resting State and Diffusion-Based Abnormalities in Borderline Personality Disorder

BACKGROUND The psychological profile of patients with borderline personality disorder (BPD), with impulsivity and emotional dysregulation as core symptoms, has guided the search for abnormalities in specific brain areas such as the hippocampal-amygdala complex and the frontomedial cortex. However, whole-brain imaging studies so far have delivered highly heterogeneous results involving different brain locations. METHODS Functional resting-state and diffusion magnetic resonance imaging data were acquired in patients with BPD and in an equal number of matched control subjects (n = 60 for resting and n = 43 for diffusion). While mean diffusivity and fractional anisotropy brain images were generated from diffusion data, amplitude of low-frequency fluctuations and global brain connectivity images were used for the first time to evaluate BPD-related brain abnormalities from resting functional acquisitions. RESULTS Whole-brain analyses using a p = .05 corrected threshold showed a convergence of alterations in BPD patients in genual and perigenual structures, with frontal white matter fractional anisotropy abnormalities partially encircling areas of increased mean diffusivity and global brain connectivity. Additionally, a cluster of enlarged amplitude of low-frequency fluctuations (high resting activity) was found involving part of the left hippocampus and amygdala. In turn, this cluster showed increased resting functional connectivity with the anterior cingulate. CONCLUSIONS With a multimodal approach and without using a priori selected regions, we prove that structural and functional abnormality in BPD involves both temporolimbic and frontomedial structures as well as their connectivity. These structures have been previously related to behavioral and clinical symptoms in patients with BPD.

Negative reward expectations in Borderline Personality Disorder patients: neurophysiological evidence.

Borderline Personality Disorder (BPD) patients present profound disturbances in affect regulation and impulse control which could reflect a dysfunction in reward-related processes. The current study investigated these processes in a sample of 18 BPD patients and 18 matched healthy controls, using an event-related brain potentials methodology. Results revealed a reduction in the amplitude of the Feedback-Related Negativity of BPD patients, which is a neurophysiological index of the impact of negative feedback in reward-related tasks. This reduction, in the effect of negative feedback in BPD patients, was accompanied by a different behavioral pattern of risk choice compared to healthy participants. These findings confirm a dysfunctional reward system in BDP patients, which might compromise their capacity to build positive expectations of future rewards and decision making.

The role of hypothalamus–pituitary–adrenal genes and childhood trauma in borderline personality disorder

Current knowledge suggests that borderline personality disorder (BPD) results from the interaction between genetic and environmental factors. Research has mainly focused on monoaminergic genetic variants and their modulation by traumatic events, especially those occurring during childhood. However, to the best of our knowledge, there are no studies on the genetics of hypothalamus–pituitary–adrenal (HPA) axis, despite its vulnerability to early stress and its involvement in BPD pathogenesis. The aim of this study was to investigate the contribution of genetic variants in the HPA axis and to explore the modulating effect of childhood trauma in a large sample of BPD patients and controls. DNA was obtained from a sample of 481 subjects with BPD and 442 controls. Case–control differences in allelic frequencies of 47 polymorphisms in 10 HPA axis genes were analysed. Modulation of genetic associations by the presence of childhood trauma was also investigated by dividing the sample into three groups: BPD with trauma, BPD without trauma and controls. Two FKBP5 polymorphisms (rs4713902-C and rs9470079-A) showed significant associations with BPD. There were also associations between BPD and haplotype combinations of the genes FKBP5 and CRHR1. Two FKBP5 alleles (rs3798347-T and rs10947563-A) were more frequent in BPD subjects with history of physical abuse and emotional neglect and two CRHR2 variants (rs4722999-C and rs12701020-C) in BPD subjects with sexual and physical abuse. Our findings suggest a contribution of HPA axis genetic variants to BPD pathogenesis and reinforce the hypothesis of the modulating effect of childhood trauma in the development of this disorder.

Preserved Error-Monitoring in Borderline Personality Disorder Patients with and without Non-Suicidal Self-Injury Behaviors.

Background The presence of non-suicidal self-injury acts in Borderline Personality Disorder (BPD) is very prevalent. These behaviors are a public health concern and have become a poorly understood phenomenon in the community. It has been proposed that the commission of non-suicidal self-injury might be related to a failure in the brain network regulating executive functions. Previous studies have shown that BPD patients present an impairment in their capacity to monitor actions and conflicts associated with the performance of certain actions, which suppose an important aspect of cognitive control. Method We used Event Related Potentials to examine the behavioral and electrophysiological indexes associated with the error monitoring in two BPD outpatients groups (17 patients each) differentiated according to the presence or absence of non-suicidal self-injury behaviors. We also examined 17 age- and intelligence- matched healthy control participants. Results The three groups did not show significant differences in event-related potentials associated with errors (Error-Related Negativity and Pe) nor in theta power increase following errors. Conclusions This is the first study investigating the behavioral and electrophysiological error monitoring indexes in BPD patients characterized by their history of non-suicidal self-injury behaviors. Our results show that error monitoring is preserved in BPD patients and suggest that non-suicidal self-injury acts are not related to a dysfunction in the cognitive control mechanisms.

An exploratory association study of the influence of noradrenergic genes and childhood trauma in Borderline Personality Disorder.

This study investigated the possible association of 40 polymorphisms within 4 noradrenergic genes with BPD risk and the modulating effect of childhood trauma on these associations in 481 BPD subjects and 442 controls. COMT rs5993882, DBH rs77905 and SLC6A2 rs1814270 showed associations with BPD, which were modulated by childhood trauma. However, none of these findings survived Bonferroni correction. Further investigation is needed to clarify the involvement of these genes in BPD pathogenesis.

Validación de la versión española del McLean Screening Instrument for Borderline Personality Disorder

INTRODUCTION Borderline personality disorder (BPD) is a common and severe mental illness. Early detection is important and reliable screening instruments are required. To date, however, there has been no evidence of any specific BPD screening tool validated for the Spanish-speaking population. The McLean Screening Instrument for Borderline Personality Disorder (MSI-BPD) is a 10-item self-report questionnaire that can detect the presence of BPD in a reliable and quick manner. The aim of the present study is the validation of the MSI-BPD for its use in the Spanish-speaking population. METHOD Psychometric properties of the MSI-BPD Spanish version were examined in a sample of 344 participants (170 outpatients with the possible diagnosis of BPD and 174 healthy controls). RESULTS Exploratory factor analysis revealed the existence of a bi-factorial structure. The scale showed a high internal consistency (KR-20=0.873) and an optimal test-retest reliability (ICC=0.87). Using logistic regression analyses and taking the DIB-R as reference, a best cut-off of 7 was determined, obtaining a good sensitivity (0.71) and specificity (0.68). The area under the curve, was 0.742 (95% CI 0.660-0.824). The discriminant analysis showed a classification ability of 72.8%. CONCLUSIONS The Spanish version of the MSI-BPD has good psychometric properties as a measure for the screening of BPD. Its ease and quickness of use make it valuable to detect the presence of BPD in clinical and research settings.

Abnormalities in gray matter volume in patients with borderline personality disorder and their relation to lifetime depression: A VBM study.

Background Structural imaging studies of borderline personality disorder (BPD) have found regions of reduced cortical volume, but these have varied considerably across studies. Reduced hippocampus and amygdala volume have also been a regular finding in studies using conventional volumetric measurement. How far comorbid major depression, which is common in BPD and can also affect in brain structure, influences the findings is not clear. Methods Seventy-six women with BPD and 76 matched controls were examined using whole-brain voxel-based morphometry (VBM). The hippocampus and amygdala were also measured, using both conventional volume measurement and VBM within a mask restricted to these two subcortical structures. Lifetime history of major depression was assessed using structured psychiatric interview. Results At a threshold of p = 0.05 corrected, the BPD patients showed clusters of volume reduction in the dorsolateral prefrontal cortex bilaterally and in the pregenual/subgenual medial frontal cortex. There was no evidence of volume reductions in the hippocampus or amygdala, either on conventional volumetry or using VBM masked to these regions. Instead there was evidence of right-sided enlargement of these structures. No significant structural differences were found between patients with and without lifetime major depression. Conclusions According to this study, BPD is characterized by a restricted pattern of cortical volume reduction involving the dorsolateral frontal cortex and the medial frontal cortex, both areas of potential relevance for the clinical features of the disorder. Previous findings concerning reduced hippocampus and amygdala volume in the disorder are not supported. Brain structural findings in BPD do not appear to be explainable on the basis of history of associated lifetime major depression.

Exploring the relationship between non suicidal self-injury and borderline personality traits in young adults

Non-suicidal self-injury (NSSI) is highly prevalent during late adolescence and young adulthood. There is some evidence of a link between NSSI and Borderline Personality Disorder (BPD), but little is known about the association between BPD traits and the various functions that maintain NSSI. The main purpose of this study was to explore the association between borderline personality traits and NSSI functions in a sample of college students. We also compared NSSI functions in college students who engaged in NSSI to those in an age-matched sample of BPD patients. This study included a total of 238 college students and 36 BPD patients. Participants were asked to complete a number of clinical measures. In the non-clinical sample, BPD features were more pronounced in the presence of NSSI, and we observed a differential relationship between NSSI functions and psychopathological BPD-traits. The NSSI clinical variables most strongly associated with BPD were frequency, variety of methods and severity, but not age of onset. Our results provide new information on the relationship between BPD and NSSI in young adults, and could be used to improve the early detection of vulnerable BPD-individuals and in planning NSSI treatment.