RESUMEN
BACKGROUND: Borderline personality disorder (BPD) is a mental health condition characterized by an inability to regulate emotions or accurately process the emotional states of others. Previous neuroimaging studies using classical univariate analyses have tied such emotion dysregulation to aberrant activity levels in the amygdala of patients with BPD. However, multivariate analyses have not yet been used to investigate how representational spaces of emotion information may be systematically altered in patients with BPD. METHODS: Patients with BPD performed an emotional face matching task while undergoing MRI before and after a 10-week inpatient program of dialectical behavioural therapy. Representational similarity analysis (RSA) was applied to activity patterns (evoked by angry, fearful, neutral and surprised faces) in the amygdala and temporo-occipital fusiform gyrus of patients with BPD and in the amygdala of healthy controls. RESULTS: We recruited 15 patients with BPD (8 females, 6 males, 1 transgender male) to participate in the study, and we obtained a neuroimaging data set for 25 healthy controls for a comparative analysis. The RSA of the amygdala revealed a negative bias in the underlying affective space (in that activity patterns evoked by angry, fearful and neutral faces were more similar to each other than to patterns evoked by surprised faces), which normalized after therapy. This bias-to-normalization effect was present neither in activity patterns of the temporo-occipital fusiform gyrus of patients nor in amygdalar activity patterns of healthy controls. LIMITATIONS: Larger samples and additional questionnaires would help to better characterize the association between specific aspects of therapy and changes in the neural representational space. CONCLUSION: Our findings suggest a more refined role for the amygdala in the pathological processing of perceived emotions and may provide new diagnostic and prognostic imaging-based markers of emotion dysregulation and personality disorders.Clinical trial registration: DRKS00019821, German Clinical Trials Register (Deutsches Register Klinischer Studien).
Asunto(s)
Trastorno de Personalidad Limítrofe , Terapia Conductual Dialéctica , Femenino , Humanos , Masculino , Trastorno de Personalidad Limítrofe/diagnóstico por imagen , Trastorno de Personalidad Limítrofe/terapia , Trastorno de Personalidad Limítrofe/patología , Emociones/fisiología , Amígdala del Cerebelo/diagnóstico por imagen , Amígdala del Cerebelo/patología , Ira , Imagen por Resonancia MagnéticaRESUMEN
BACKGROUND: Neuroimaging, especially diffusion tensor imaging (DTI), has emerged as a helpful tool in assessing and characterizing white matter (WM) integrity. The resultant early treatment from early diagnosis is crucial because treatment is often more efficacious. Borderline personality disorder (BPD) is a challenging disorder to diagnose and treat, and has been reported to have various neurobiologic abnormalities. We conducted a search of the literature to review WM pathology findings in BPD. METHODS: A search was conducted to identify systematic reviews and meta-analyses published from January 2000 to September 2019 that assessed WM integrity in BPD. RESULTS: Four studies were included. One study demonstrated no difference in WM between BPD and healthy controls. Another study found decreased fractional anisotropy (FA) within the corpus callosum (CC) and orbitofrontal regions. A subsequent randomized controlled trial reported a decrease in FA within the fornix, CC, and right superior/anterior corona radiata with associated increase in radial diffusivity in the left anterior thalamic radiation. The fourth study found a decrease in the axial diffusivity within the cingulum, inferior longitudinal fasciculus, and inferior frontoccipital fasciculus. CONCLUSIONS: Our review concludes that BPD is associated with measurable WM pathology. Methods such as DTI might emerge as useful tools in the management of BPD. More controlled studies are needed to validate our conclusions.
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Trastorno de Personalidad Limítrofe/patología , Imagen de Difusión Tensora , Sustancia Blanca/patología , Anisotropía , HumanosRESUMEN
Neuroimaging research provides evidence of grey matter changes in the prefrontal-limbic network in borderline personality disorder (BPD), yet research scarcely examines the white matter (WM) within this circuitry. The present study aimed to explore WM in prefrontal-limbic brain networks within BPD. Quantitative diffusion tensor imaging (DTI-MRI) measures of fractional anisotropy (FA) and mean diffusion (MD) were used to analyze the neural pathways in fifteen individuals with BPD (Mâ¯=â¯25, SDâ¯=â¯6.76), in comparison to thirteen healthy individuals (Mâ¯=â¯27.92, SDâ¯=â¯8.41). Quantitative DTI-MRI measures of FA and MD were evaluated for the cingulum, the fornix, the corpus callosum (CC), the inferior longitudinal fasciculus (ILF), the superior longitudinal fasciculus (SLF) and the uncinate fasciculus (UF). Lower FA values for both the left and the right cingulum, the genu, body, and splenium of the CC, left ILF and right SLF were found in BPD, compared to healthy individuals. MD values were higher for the genu and splenium of the CC in BPD. The findings indicate that a large-scale emotional brain network is affected in BPD with alterations in MD and FA of WM prefrontal-limbic pathways of the heteromodal association cortex involved in emotion processing and emotion regulation.
Asunto(s)
Trastorno de Personalidad Limítrofe/patología , Cuerpo Calloso/patología , Regulación Emocional , Sistema Límbico/patología , Red Nerviosa/patología , Corteza Prefrontal/patología , Sustancia Blanca/patología , Adolescente , Adulto , Trastorno de Personalidad Limítrofe/diagnóstico por imagen , Cuerpo Calloso/diagnóstico por imagen , Imagen de Difusión Tensora , Femenino , Humanos , Sistema Límbico/diagnóstico por imagen , Persona de Mediana Edad , Red Nerviosa/diagnóstico por imagen , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/patología , Corteza Prefrontal/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen , Adulto JovenRESUMEN
BACKGROUND: Whether borderline personality disorder (BPD) and bipolar disorder are the same or different disorders lacks consistency.AimsTo detect whether grey matter volume (GMV) and grey matter density (GMD) alterations show any similarities or differences between BPD and bipolar disorder. METHOD: Web-based publication databases were searched to conduct a meta-analysis of all voxel-based studies that compared BPD or bipolar disorder with healthy controls. We included 13 BPD studies (395 patients with BPD and 415 healthy controls) and 47 bipolar disorder studies (2111 patients with bipolar disorder and 3261 healthy controls). Peak coordinates from clusters with significant group differences were extracted. Effect-size signed differential mapping meta-analysis was performed to analyse peak coordinates of clusters and thresholds (P < 0.005, uncorrected). Conjunction analyses identified regions in which disorders showed common patterns of volumetric alteration. Correlation analyses were also performed. RESULTS: Patients with BPD showed decreased GMV and GMD in the bilateral medial prefrontal cortex network (mPFC), bilateral amygdala and right parahippocampal gyrus; patients with bipolar disorder showed decreased GMV and GMD in the bilateral medial orbital frontal cortex (mOFC), right insula and right thalamus, and increased GMV and GMD in the right putamen. Multi-modal analysis indicated smaller volumes in both disorders in clusters in the right medial orbital frontal cortex. Decreased bilateral mPFC in BPD was partly mediated by patient age. Increased GMV and GMD of the right putamen was positively correlated with Young Mania Rating Scale scores in bipolar disorder. CONCLUSIONS: Our results show different patterns of GMV and GMD alteration and do not support the hypothesis that bipolar disorder and BPD are on the same affective spectrum.Declaration of interestNone.
Asunto(s)
Trastorno Bipolar/patología , Trastorno de Personalidad Limítrofe/patología , Encéfalo/patología , Sustancia Gris/patología , Adulto , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Neuroimagen , Adulto JovenRESUMEN
Self-inflicted injury (SII) in adolescence is a serious public health concern that portends prospective vulnerability to internalizing and externalizing psychopathology, borderline personality development, suicide attempts, and suicide. To date, however, our understanding of neurobiological vulnerabilities to SII is limited. Behaviorally, affect dysregulation is common among those who self-injure. This suggests ineffective cortical modulation of emotion, as observed among adults with borderline personality disorder. In borderline samples, structural and functional abnormalities are observed in several frontal regions that subserve emotion regulation (e.g., anterior cingulate, insula, dorsolateral prefrontal cortex). However, no volumetric analyses of cortical brain regions have been conducted among self-injuring adolescents. We used voxel-based morphometry to compare cortical gray matter volumes between self-injuring adolescent girls, ages 13-19 years (n = 20), and controls (n = 20). Whole-brain analyses revealed reduced gray matter volumes among self-injurers in the insular cortex bilaterally, and in the right inferior frontal gyrus, an adjacent neural structure also implicated in emotion and self-regulation. Insular and inferior frontal gyrus gray matter volumes correlated inversely with self-reported emotion dysregulation, over-and-above effects of psychopathology. Findings are consistent with an emotion dysregulation construal of SII, and indicate structural abnormalities in some but not all cortical brain regions implicated in borderline personality disorder among adults.
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Trastorno de Personalidad Limítrofe/diagnóstico por imagen , Corteza Cerebral/diagnóstico por imagen , Conducta Autodestructiva/diagnóstico por imagen , Adolescente , Trastorno de Personalidad Limítrofe/patología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Corteza Cerebral/patología , Emociones , Femenino , Lóbulo Frontal/diagnóstico por imagen , Lóbulo Frontal/patología , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Giro del Cíngulo/diagnóstico por imagen , Giro del Cíngulo/patología , Humanos , Imagen por Resonancia Magnética , Tamaño de los Órganos , Desarrollo de la Personalidad , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/patología , Estudios Prospectivos , Conducta Autodestructiva/patología , Adulto JovenRESUMEN
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.
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Terapia Conductista , Trastorno de Personalidad Limítrofe/patología , Trastorno de Personalidad Limítrofe/terapia , Corteza Cerebral/patología , Sustancia Gris/patología , Adulto , Femenino , Humanos , Imagen por Resonancia Magnética , Neuroimagen , Adulto JovenRESUMEN
Affective hyper-reactivity and impaired cognitive control of emotional material are core features of borderline personality disorder (BPD). A high percentage of individuals with BPD experience stress-related dissociation, including emotional numbing and memory disruptions. So far little is known about how dissociation influences the neural processing of emotional material in the context of a working memory task in BPD. We aimed to investigate whole-brain activity and amygdala functional connectivity (FC) during an Emotional Working Memory Task (EWMT) after dissociation induction in un-medicated BPD patients compared to healthy controls (HC). Using script-driven imagery, dissociation was induced in 17 patients ('BPD_D'), while 12 patients ('BPD_N') and 18 HC were exposed to neutral scripts during fMRI. Afterwards, participants performed the EWMT with neutral vs. negative IAPS pictures vs. no distractors. Main outcome measures were behavioral performance (reaction times, errors) and whole-brain activity during the EWMT. Psychophysiological interaction analysis was used to examine amygdala connectivity during emotional distraction. BPD patients after dissociation induction showed overall WM impairments, a deactivation in bilateral amygdala, and lower activity in left cuneus, lingual gyrus, and posterior cingulate than BPD_N, along with stronger left inferior frontal gyrus activity than HC. Furthermore, reduced amygdala FC with fusiform gyrus and stronger amygdala FC with right middle/superior temporal gyrus and left inferior parietal lobule was observed in BPD_D. Findings suggest that dissociation affects reactivity to emotionally salient material and WM. Altered activity in areas associated with emotion processing, memory, and self-referential processes may contribute to dissociative states in BPD.
Asunto(s)
Amígdala del Cerebelo/patología , Trastorno de Personalidad Limítrofe/complicaciones , Trastorno de Personalidad Limítrofe/patología , Trastornos Disociativos/etiología , Trastornos de la Memoria/etiología , Memoria a Corto Plazo/fisiología , Adolescente , Adulto , Amígdala del Cerebelo/diagnóstico por imagen , Análisis de Varianza , Trastorno de Personalidad Limítrofe/diagnóstico por imagen , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Trastornos de la Memoria/diagnóstico por imagen , Persona de Mediana Edad , Oxígeno/sangre , Adulto JovenRESUMEN
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.
Asunto(s)
Agresión/fisiología , Amígdala del Cerebelo/patología , Trastorno de Personalidad Limítrofe/patología , Trastorno de Personalidad Limítrofe/fisiopatología , Adulto , Amígdala del Cerebelo/diagnóstico por imagen , Análisis de Varianza , Trastorno de Personalidad Limítrofe/diagnóstico por imagen , Femenino , Lateralidad Funcional/fisiología , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Escalas de Valoración Psiquiátrica , Análisis de Regresión , Autoinforme , Factores Sexuales , Encuestas y Cuestionarios , Adulto JovenRESUMEN
BACKGROUND: Little is known about narcissistic traits in borderline personality disorder (BPD). This exploratory study aimed to illustrate the associations between total, grandiose, and vulnerable narcissism and gender, diagnostic features of BPD and narcissistic personality disorder (NPD), and psychopathology in BPD patients. SAMPLING AND METHODS: The Pathological Narcissism Inventory and psychometric measures for impulsivity, anger, borderline symptom severity, personality organization, depression, and rejection sensitivity were completed by 65 BPD patients. Statistical analyses were conducted using the t test, Pearson correlation, and multivariate regression analyses. RESULTS: Male BPD patients displayed higher narcissistic scores than females (p < 0.01). Grandiose narcissism showed a stronger association with NPD than with BPD (p < 0.01) while vulnerable narcissism was only associated with BPD (p < 0.01). Rejection sensitivity (p < 0.01) and depression (p < 0.001) predicted vulnerable narcissism. CONCLUSION: Vulnerable narcissism is closely associated with BPD and appears to be more dysfunctional than grandiose narcissism. A comprehensive consideration of both traits is recommended. Our results might help to generate hypotheses for further research on pathological narcissism in the spectrum of personality disorders. Future studies are advised to apply complementary measures and take new diagnostic approaches of DSM-5 and ICD-11 into account.
Asunto(s)
Trastorno de Personalidad Limítrofe/complicaciones , Narcisismo , Adulto , Trastorno de Personalidad Limítrofe/patología , Femenino , Humanos , Masculino , Inventario de PersonalidadRESUMEN
OBJECTIVE: Although the frontolimbic cortex has been implicated in borderline personality disorder (BPD), information about possible asymmetries in this region in patients with BPD is limited. This study aimed to examine whether frontolimbic cortex asymmetries differ between patients with BPD and healthy individuals. METHODS: The brains of 30 young adult patients with BPD and 32 healthy control subjects were scanned with magnetic resonance imaging (MRI). The participants completed self-report scales assessing impulsivity, affect intensity and other psychological variables. Gray matter volume, surface area, and cortical thickness in regions of interest (ROIs), namely anterior insula (AI) and anterior cingulate cortex (ACC) were determined and the data were probed for hemisphere-group interactions. RESULTS: Relative to controls, patients with BPD had reduced cortical thickness in left ACC and less surface area and gray matter volume in left AI. Significant group-hemisphere interactions were observed for gray matter volume and surface area of AI and for cortical thickness of ACC. Post hoc analysis showed that the BPD patients had greater frontolimbic cortex asymmetry than healthy controls; furthermore, greater asymmetry of AI&ACC correlated with a higher score in attention subscale of Barratt Impulsiveness Scale. CONCLUSION: Patients with BPD have greater frontolimbic asymmetry than healthy individuals.
Asunto(s)
Trastorno de Personalidad Limítrofe/patología , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/patología , Imagen por Resonancia Magnética , Adulto , Estudios Transversales , Femenino , Humanos , Masculino , Tamaño de los Órganos , Adulto JovenRESUMEN
BACKGROUND: Romantic relationships are one of the most interesting areas of interpersonal functioning in people with borderline personality. The aim of this narrative review was to synthesise empirical findings on this issue. SAMPLING AND METHODS: The PubMed and PsycINFO databases were searched for pertinent materials published between 1980 and March 2016. Thirty articles met the inclusion criteria. RESULTS: Several longitudinal and cross-sectional studies showed that people with borderline personality disorder (BPD) or BPD traits had more - but less prolonged - romantic relationships than people without BPD. The stable relationships of people with BPD or with BPD traits were also less satisfying and more hostile than those of people without BPD. People with BPD or BPD traits had relationships characterised by insecure attachment and passive-aggressive communications. Personality disorders and anxious attachment were more prevalent among the partners of people with BPD or with BPD traits when compared with partners of people without BPD. CONCLUSION: Unstable and chaotic romantic relationships are at the core of interpersonal dysfunction in BPD. More longitudinal research is needed to delineate the relationship between BPD symptoms and romantic relationship dysfunction, including the modulating role of the partner's clinical features in such an association.
Asunto(s)
Trastorno de Personalidad Limítrofe/complicaciones , Trastorno de Personalidad Limítrofe/patología , Estudios Transversales , Femenino , Humanos , Relaciones Interpersonales , Estudios Longitudinales , MasculinoRESUMEN
BACKGROUND: Auditory verbal hallucinations (AVH) are experienced by 21-54% of patients diagnosed with a borderline personality disorder (BPD), and ensuing distress is often high. Little is known about the beliefs these patients foster about their voices, and the influence thereof on distress and need for hospitalisation. METHODS: In a convenience sample of 38 BPD outpatients with AVH, data were collected with the aid of the Psychotic Symptom Rating Scales (PSYRATS), Beliefs about Voices Questionnaire (BAVQ), Social Comparison Rating Scale (SCRS), and Voice Power Differential Scale (VPDS). RESULTS: The majority of patients with BPD who experience AVH rate their voices as malevolent and omnipotent, and higher in social rank than themselves. Moreover, their resistance against them tends to be high. These parameters correlate positively and significantly with high levels of distress experienced in relation to these AVH. The need for hospitalisation, in turn, is associated with high scores for omnipotence of the voices and distress due to AVH. However, these findings could not be confirmed in regression analyses. CONCLUSIONS: As negative beliefs can be altered with cognitive-behavioural therapy (CBT), we expect CBT to be beneficial in the treatment of AVH in BPD patients, whether or not in combination with antipsychotic medication.
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Trastorno de Personalidad Limítrofe/complicaciones , Terapia Cognitivo-Conductual/métodos , Alucinaciones/etiología , Trastornos Psicóticos/diagnóstico , Adulto , Trastorno de Personalidad Limítrofe/patología , Estudios Transversales , Femenino , Humanos , MasculinoRESUMEN
AIMS: The study aimed to investigate childhood maltreatment, sex, and borderline personality disorder (BPD) symptoms as prospective predictors of adolescent hypothalamic-pituitary-adrenal (HPA) axis reactivity. METHOD: A sample of 69 adolescents (30 female and 39 male) were selected from a larger longitudinal study of adolescent development and assessed at 3 time points. BPD symptoms were assessed at T1 (approx. 12.5 years), childhood maltreatment was assessed at T2 (approx. 14.9 years), and multiple assessments of salivary cortisol (cortisol awakening response; CAR) were undertaken at T3 (approx. 15.5 years). RESULTS: Multivariate linear regression analysis revealed a significant main effect for childhood maltreatment but not for early BPD symptoms as a predictor of lower CAR in adolescence (p = 0.047). The association between childhood maltreatment and attenuated CAR was moderated by both early BPD symptoms (p = 0.024; no childhood maltreatment-dependent attenuation of CAR in the presence of BPD symptoms) and sex (p = 0.012; childhood maltreatment-dependent attenuation of CAR in females only). Furthermore, a 3-way BPD × childhood maltreatment × sex interaction (p = 0.041) indicated that the moderating effect of BPD symptoms was present in females only. CONCLUSION: These findings indicate that attenuation of the HPA axis occurs as a response to early maltreatment rather than being related to the early occurrence of BPD pathology. Traumatized female individuals with BPD symptoms might bypass adaptive HPA axis attenuation.
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Trastorno de Personalidad Limítrofe/metabolismo , Maltrato a los Niños/psicología , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisario/fisiopatología , Adolescente , Trastorno de Personalidad Limítrofe/patología , Niño , Femenino , Identidad de Género , Humanos , Estudios Longitudinales , Masculino , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
OBJECTIVE: The pathogenesis of borderline personality disorder (BPD) is not well understood. We examined the microstructure of white matter in patients with BPD. METHOD: Treatment-naïve young adult with BPD (N = 30) and young-adult healthy controls (HCs; N = 31) were subjected diffusion tensor imaging (DTI). Microstructural parameters were analyzed via tract-based spatial statistics (TBSS) and post hoc tractography. RESULTS: TBSS analysis revealed that, relative to the HC group, the BPD group had significantly lower fractional anisotropy (FA) values in the genu and body of the corpus callosum (CC), right superior corona radiate, right anterior corona radiate, as well as higher radial diffusivity (RD) in the left anterior thalamic radiation. Tractography showed that FA values of fiber bundles passing through the fornix were significantly reduced in BPD group relative to HCs. No significant correlations were observed between clinical symptom and DTI indices in BPD group (FDR corrected). CONCLUSION: Focal microstructural alterations were found in BPD group, mainly in the limbic system and CC. The present findings support the fronto-limbic disconnectivity hypothesis and suggest that abnormal maturation of white matter structures may play an important role in mechanism of BPD.
Asunto(s)
Trastorno de Personalidad Limítrofe/patología , Cuerpo Calloso/patología , Sistema Límbico/patología , Sustancia Blanca/patología , Adulto , Trastorno de Personalidad Limítrofe/diagnóstico por imagen , Cuerpo Calloso/diagnóstico por imagen , Imagen de Difusión Tensora , Femenino , Humanos , Sistema Límbico/diagnóstico por imagen , Masculino , Sustancia Blanca/diagnóstico por imagen , Adulto JovenRESUMEN
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.
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Trastorno de Personalidad Limítrofe , Maltrato a los Niños/psicología , Sistema Hipotálamo-Hipofisario/metabolismo , Sistema Hipófiso-Suprarrenal/metabolismo , Adulto , Trastorno de Personalidad Limítrofe/etiología , Trastorno de Personalidad Limítrofe/genética , Trastorno de Personalidad Limítrofe/patología , Estudios de Casos y Controles , Niño , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Genotipo , Humanos , Masculino , Escalas de Valoración Psiquiátrica , Receptores de Hormona Liberadora de Corticotropina/genética , Proteínas de Unión a Tacrolimus/genética , Adulto JovenRESUMEN
Previous research suggests disturbed emotional learning and memory in borderline personality disorder (BPD). Studies investigating the neural correlates of aversive differential delay conditioning in BPD are currently lacking. We aimed to investigate acquisition, within-session extinction, between-session extinction recall, and reacquisition. We expected increased activation in the insula, amygdala, and anterior cingulate, and decreased prefrontal activation in BPD patients. During functional magnetic resonance imaging, 27 medication-free female BPD patients and 26 female healthy controls (HC) performed a differential delay aversive conditioning paradigm. An electric shock served as unconditioned stimulus, two neutral pictures as conditioned stimuli (CS+/CS-). Dependent variables were blood-oxygen-level-dependent response, skin conductance response (SCR), and subjective ratings (valence, arousal). No significant between-group differences in brain activation were found [all p(FDR) > 0.05]. Within-group comparisons for CS+unpaired > CS- revealed increased insula activity in BPD patients but not in HC during early acquisition; during late acquisition, both groups recruited fronto-parietal areas [p(FDR) < 0.05]. During extinction, BPD patients rated both CS+ and CS- as significantly more arousing and aversive than HC and activated the amygdala in response to CS+. In contrast, HC showed increased prefrontal activity in response to CS+ > CS during extinction. During extinction recall, there was a trend for stronger SCR to CS+ > CS in BPD patients. Amygdala habituation to CS+paired (CS+ in temporal contingency with the aversive event) during acquisition was found in HC but not in patients. Our findings suggest altered temporal response patterns in terms of increased vigilance already during early acquisition and delayed extinction processes in individuals with BPD.
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Trastorno de Personalidad Limítrofe/patología , Trastorno de Personalidad Limítrofe/fisiopatología , Encéfalo/diagnóstico por imagen , Condicionamiento Clásico/fisiología , Imagen por Resonancia Magnética , Adulto , Análisis de Varianza , Animales , Trastorno de Personalidad Limítrofe/diagnóstico por imagen , Femenino , Respuesta Galvánica de la Piel , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Oxígeno/sangre , Escalas de Valoración Psiquiátrica , Adulto JovenRESUMEN
Borderline personality disorder (BPD) is a serious psychic disease with a high risk for suicide. DNA methylation is a hallmark for aberrant epigenetic regulation and could be involved in the etiology of BPD. Previously, it has been reported that increased DNA methylation of neuropsychiatric genes is found in the blood of patients with BPD compared to healthy controls. Here, we analyzed DNA methylation patterns of the ribosomal RNA gene (rDNA promoter region and 5'-external transcribed spacer/5'ETS) and the promoter of the proline rich membrane anchor 1 gene (PRIMA1) in peripheral blood samples of 24 female patients (mean age (33 ± 11) years) diagnosed with DSM-IV BPD and in 11 female controls (mean age (32 ± 7) years). A significant aberrant methylation of rDNA and PRIMA1 was revealed for BPD patients using pyrosequencing. For the promoter of PRIMA1, the average methylation of six CpG sites was 1.6-fold higher in BPD patients compared to controls. In contrast, the methylation levels of the rDNA promoter region and the 5'ETS were significantly lower (0.9-fold) in patients with BPD compared to controls. Thus, for nine CpGs located in the rDNA promoter region and for four CpGs at the 5'ETS decreased methylation was found in peripheral blood of patients compared to controls. Our results suggest that aberrant methylation of rDNA and PRIMA1 is associated with the pathogenesis of BPD.
Asunto(s)
Trastorno de Personalidad Limítrofe/genética , Metilación de ADN , ADN Ribosómico/genética , Proteínas de la Membrana/genética , Proteínas del Tejido Nervioso/genética , Regiones Promotoras Genéticas , Adolescente , Adulto , Trastorno de Personalidad Limítrofe/patología , Islas de CpG , Epigénesis Genética , Femenino , Humanos , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: A dysfunctional network of prefrontal and (para-)limbic brain region has been suggested to underlie emotional dysregulation in borderline personality disorder (BPD). Abnormal activity in this network may be due to structural alterations in white-matter tracts connecting prefrontal and (para-)limbic brain regions. To test this hypothesis, we investigated the structural integrity of major white-matter tracts connecting these regions in BPD. METHOD: Using diffusion tensor imaging, we investigated fractional anisotropy (FA), axonal anisotropy (AD) and radial diffusivity (RD) in the uncinate fasciculus, the major white-matter tract connecting (para-)limbic and prefrontal brain regions, in 26 healthy controls (HC) and 26 BPD participants. To clarify the specificity of possible white-matter alterations among HC and BPD participants, FA, AD and RD were also investigated in the cingulum. RESULTS: We found distinct structural alterations in the uncinate fasciculus but not in the cingulum of BPD participants. Compared to HC participants, BPD participants showed lower FA and higher RD in the uncinate fasciculus. By contrast, AD did not differ in the uncinate fasciculus of HC and BPD participants. CONCLUSIONS: Our finding of abnormal FA and RD in the uncinate fasciculus indicates distinct white-matter alterations in BPD, presumably due to stress-induced myelin degeneration in the aftermath of stressful life events. Although these alterations may account for abnormal activity in brain regions implicated in emotion dysregulation, such as the amygdala, anterior cingulate cortex and prefrontal cortex, it remains to be determined whether these alterations are specific for BPD.
Asunto(s)
Amígdala del Cerebelo/patología , Trastorno de Personalidad Limítrofe/patología , Giro del Cíngulo/patología , Corteza Prefrontal/patología , Sustancia Blanca/patología , Adulto , Imagen de Difusión Tensora , Femenino , Humanos , Vías Nerviosas/patología , Adulto JovenRESUMEN
Uncontrollable emotional lability and impulsivity are a paramount phenomenon of Borderline Personality Disorder (BPD). This paper aims to review theories that entertain emotion dysregulation as the core deficit of BPD and a key factor in the etiology of BPD, in order, then, to propose the author's own theory, which arguably transcends certain limitations of the earlier ones. The author asserts that his psychodynamic theory explains the symptoms of BPD more thoroughly and it inspires a more parsimonious interpretation of brain imaging findings. In closing, the author draws implications of the proposed theory for clinical practice. He reports an efficacy study for treatment of emotion dysregulation based on that theory.
Asunto(s)
Síntomas Afectivos/patología , Síntomas Afectivos/terapia , Trastorno de Personalidad Limítrofe/patología , Trastorno de Personalidad Limítrofe/terapia , Terapia Cognitivo-Conductual/métodos , Modelos Psicológicos , Síntomas Afectivos/fisiopatología , Trastorno de Personalidad Limítrofe/fisiopatología , Encéfalo/patología , Encéfalo/fisiopatología , Mapeo Encefálico , Femenino , Humanos , Conducta Impulsiva , Masculino , Aislamiento Social , Habilidades SocialesRESUMEN
BACKGROUND: Animal and human studies have suggested that hippocampal subfields are differentially vulnerable to stress, but subfield volume has not been investigated in patients with borderline personality disorder (BPD). Based on the putative role of stressful life events as vulnerability factors for BPD, we hypothesized that patients with BPD would exhibit reduced volumes for the stress-sensitive dentate gyrus (DG) and the cornu ammonis (CA) 3 subfields volumes, and that these volumes would be associated with traumatic childhood experiences. METHODS: All participants underwent 3 T magnetic resonance imaging. Hippocampal subfield volumes were estimated using an automated and validated segmentation algorithm implemented in FreeSurfer. Age and total subcortical grey matter volume were covariates. We assessed traumatic childhood experiences using the Childhood Trauma Questionnaire (CTQ). RESULTS: A total of 18 women with BPD and 21 healthy control women were included in the study. Only 1 patient had comorbid posttraumatic stress disorder (PTSD). The volumes of the left (p = 0.005) and right (p = 0.011) DG-CA4 and left (p = 0.007) and right (p = 0.005) CA2-3 subfields were significantly reduced in patients compared with controls. We also found significant group differences for the left (p = 0.032) and right (p = 0.028) CA1, but not for other hippocampal subfields. No associations were found between CTQ scores and subfield volumes. LIMITATIONS: The self-reported CTQ might be inferior to more comprehensive assessments of traumatic experiences. The sample size was moderate. CONCLUSION: The volumes of stress-sensitive hippocampal subfields are reduced in women with BPD without PTSD. However, the degree to which childhood trauma is responsible for these changes is unclear.