Pathophysiology Of Borderline Personality Disorder Research Articles

Neurophysiological insights into impaired mentalization in borderline personality disorder an electroencephalography study.

Borderline personality disorder (BPD) is characterized by interpersonal and emotional instabilities, recurring suicidal tendencies, and feelings of emptiness. Childhood adverse event is reported in 70%-80% of cases involving BPD. Furthermore, the deficiency in mentalization capacity plays a significant role in emotion dysregulation and social interaction problems within individuals with BPD. This study explored the relationship among childhood adverse experiences, mentalization capacity, and neurophysiological activity in patients with BPD. Resting-state electroencephalography was used to identify the neural correlates associated with childhood adversity and mentalization deficits. The participants included 45 patients with BPD and 15 healthy controls. The BPD group exhibited reduced alpha activity during eyes-closed rest, indicating heightened arousal even during relaxation. Correlations were found between the power spectral density (PSD) and mentalization capacity in the delta and theta ranges, suggesting an association between PSD and emotional awareness and expression. Gamma activity negatively correlated with psychic equivalence, implying a blurring of the boundaries between internal mental experiences and the external world. These findings offer insights into the pathophysiology of BPD, provide potential diagnostic markers, and suggest personalized treatment approaches based on mentalization traits.

The Role of the Hippocampus in Borderline Personality Disorder: Structural and Functional Abnormalities

This review article discusses the structural and functional abnormalities observed in the hippocampus of individuals with borderline personality disorder (BPD). The hippocampus plays a critical role in regulating emotions and memories, which has been implicated in the pathophysiology of BPD. The review summarizes the findings from various studies that have used neuroimaging techniques to investigate the hippocampus in BPD. The results suggest that individuals with BPD exhibit reduced hippocampal volume, altered hippocampal activation patterns, and disrupted connectivity with other brain regions. These abnormalities have been linked to several clinical features of BPD, including emotional dysregulation, impulsivity, and unstable self-image. The review also discusses potential mechanisms underlying these abnormalities, such as childhood trauma and chronic stress. Overall, this review highlights the importance of the hippocampus in the etiology of BPD and emphasizes the need for further research to understand its role in this complex disorder fully.

Efficacy of naltrexone in borderline personality disorder, a retrospective analysis in inpatients.

The endogenous opioid system is assumed to be involved in the pathophysiology of borderline personality disorder (BPD), and opioid antagonists may improve core features of BPD. The aim of this retrospective chart analysis was to evaluate the relative contribution of the opioid antagonist naltrexone and other psychotropic drugs in the improvement of overall symptomatology in BPD. One hundred sixty-one inpatients with BPD treated between January 2010 and October 2013 were classified as either treatment responders or non-responders. Treatment responders were defined as subjects with significant improvements in four or more symptoms from a defined symptom list. The relative contribution of all psychotropic drugs to improvement of BPD symptomatology was assessed by means of a stepwise logistic regression. None of the drugs applied contributed significantly to improvement, with the exception of naltrexone (odds ratio [OR] 43.2, p≤0.0001). Patients treated with naltrexone (N=55, 34%) recovered significantly more often. Higher doses of naltrexone were more effective (OR 791.8, p≤0.0001) than lower doses (OR 26.6, p≤0.0001); however, even low-dose treatment was better than any other pharmacological treatment. Naltrexone was associated with improvement in BPD in a dose-dependent manner. The present study provides additional evidence that dysregulation of the endogenous opioid system is implicated in the pathophysiology of BPD symptoms.

Neurophysiological activity following rewards and losses among female adolescents and young adults with borderline personality disorder.

Borderline personality disorder (BPD) is a complex and debilitating psychiatric illness. Prior research in adults has shown that neurophysiological deficits in feedback processing and learning from rewards may be central to the development of BPD; however, little research has examined these markers in adolescents and young adults with BPD. The present study used event-related potentials and time-frequency decomposition analysis to probe neural responses to wins and losses in a guessing task among 68 females (13 to 23 years old) either with BPD (n = 35) or no history of mental disorders (healthy control [HC]; n = 33). Participants completed a guessing task wherein they won and lost money at equal frequencies while electroencephalogram (EEG) data were acquired. Adolescents and young adults with BPD showed a smaller differentiation between wins and losses in the reward positivity (RewP) relative to HCs. Using time-frequency decomposition, we isolated distinct frequency bands sensitive to wins (delta = < 3Hz) and losses (theta = 4 Hz to 7 Hz). Compared with BPD participants, HCs showed significantly larger delta power to wins, specifically. The groups did not differ in delta power to losses, nor theta power to wins or losses. Collectively, findings implicate altered reward processing in the pathophysiology of BPD and may inform early identification and targeted intervention. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Amygdala and dlPFC abnormalities, with aberrant connectivity and habituation in response to emotional stimuli in females with BPD

BackgroundLittle is known about the frontolimbic abnormalities thought to underlie borderline personality disorder (BPD). We endeavoured to study regional responses, as well as their connectivity and habituation during emotion processing. Methods14 BPD patients and 14 normal female controls (NC) controlled for menstrual phase underwent emotion-induction during an fMRI task using standardised images in a block design. We then performed psychophysiological interaction (PPI) analysis to investigate functional connectivity. ResultsBPD patients reported more disgust in questionnaires compared to controls. Relative to NC, they showed reduced left amygdala and increased dorsolateral prefrontal cortex (dlPFC) activation to all emotions collapsed versus neutral. Habituation of ventral striatal activity to repeated emotional stimuli was observed in controls but not in BPD. Finally, in the context of disgust (but not other emotions) versus neutral, BPD patients displayed enhanced left amygdala coupling with the dlPFC and ventral striatum. LimitationsStrict inclusion criteria reduced the sample size. ConclusionsIn summary, BPD showed abnormal patterns of activation, habituation and connectivity in regions linked to emotion regulation. Amygdala deactivation may be mediated by abnormal top-down regulatory control from the dorsolateral prefrontal cortex. Aberrant emotion processing may play a unique role in the pathophysiology of BPD.

A New Perspective on the Pathophysiology of Borderline Personality Disorder: A Model of the Role of Oxytocin.

Borderline personality disorder is characterized by three domains of dysfunction: affect dysregulation, behavioral dyscontrol, and interpersonal hypersensitivity. Interpersonal hypersensitivity is associated with a (pre)attentive bias toward negative social information and, on the level of the brain, enhanced bottom-up emotion generation, while affect dysregulation results from abnormal top-down processes. Additionally, the problems of patients with borderline personality disorder in interpersonal functioning appear to be related to alterations in the (social) reward and empathy networks. There is increasing evidence that the oxytocinergic system may be involved in these domains of dysfunction and may thus contribute to borderline psychopathology and even open new avenues for targeted pharmacotherapeutic approaches. From studies in healthy and clinical subjects (including first studies with borderline personality disorder patients), the authors provide a conceptual framework for future research in borderline personality disorder that is based on oxytocinergic modulation of the following biobehavioral mechanisms: 1) the brain salience network favoring adaptive social approach behavior, 2) the affect regulation circuit normalizing top-down processes, 3) the mesolimbic circuit improving social reward experiences, and 4) modulating brain regions involved in cognitive and emotional empathy. In addition, preliminary data point to interactions between the oxytocin and cannabinoid system, with implications for pain processing. These mechanisms, which the authors believe to be modulated by oxytocin, may not be specific for borderline personality disorder but rather may be common to a host of psychiatric disorders in which disturbed parent-infant attachment is a major etiological factor.

Morphometric hemispheric asymmetry of orbitofrontal cortex in women with borderline personality disorder: A multi-parameter approach

Functional imaging studies have implicated the orbitofrontal cortex (OFC) in the pathophysiology of borderline personality disorder (BPD). To date, however, volume-based magnetic resonance imaging (MRI) studies have yielded mixed results. We used a surface-based processing approach that allowed us to measure five morphometric cortical features of the OFC, including volumetric (cortical thickness and surface area) and geometric (mean curvature, depth of sulcus, and metric distortion – three indicators of cortical folding) parameters. Participants comprised 25 female BPD patients with no other current psychiatric comorbidity and 25 age- and gender-matched healthy controls who received structural MRI scans. Images were processed using the Freesurfer package. All BPD patients had a history of comorbid psychiatric disorder(s) and were currently on medications. Compared with controls, the BPD group showed reduced cortical thickness, surface area, mean curvature, depth of sulcus, and metric distortion in the right medial OFC. In the left medial OFC, the BPD group had reduced cortical thickness and mean curvature, but increased metric distortion. This study confirmed the utility of surface-based analysis in the study of BPD cortical structures. In addition, we observed extensive structural abnormalities in the medial OFC of female subjects with BPD, findings that were most pronounced in the right OFC, with preliminary data suggesting hemispheric asymmetry.

Physical and Social Pains in Borderline Disorder and Neuroanatomical Correlates: A Systematic Review

Borderline personality disorder (BPD) is a common psychiatric disorder, the core features of which are affective dysregulation, identity disturbances, and problems in social interaction, with an intense fear of loss, abandonment, or rejection by social partners. Self-injurious behaviors (SIB), such as superficial cutting, occur in 70-80% of BPD patients, which are associated with emotional relief. Intriguingly, the majority of BPD patients report reduced or no pain associated with SIB, whereas BPD patients are over-represented in chronic pain patients. Thus, studying pain perception in such patients may help to understand the pathophysiology of BPD, but also the interaction between affective and physical dimensions of pain. We conducted a systematic review dealing with physical and social pains in BPD patients, with a special focus on neuroimaging data. SIB appear to be an inadequate strategy to regulate negative emotions that may be related to social/psychological pain, by increasing dorsolateral prefrontal cortex activation in order to regulate amygdala activation. In addition, abnormal hyperactivation of the insula is a possible trait marker of BPD, and might contribute to modified pain sensitivity. When considering psychological pain in BPD patients, neuroanatomical studies have shown a hyper-responsive subcortical limbic network and a deficient regulatory control system operating through anterior brain regions. Promising therapeutic strategies should target neuroanatomical and neurobiological dysfunctions, which lead to altered pain perception in BPD patients.

Loudness dependence of auditory evoked potentials in patients with borderline personality disorder—Impact of psychopathology

Alterations of the central serotonergic system are considered to be involved in the pathophysiology of borderline personality disorder (BPD). The loudness dependence of the N1/P2 component of auditory evoked potentials (LD) has been shown to indirectly reflect central serotonergic activity. The aim of this study was to investigate LD in patients with BPD compared to healthy controls, and to evaluate the association between LD and psychopathology such as anxiety, anger or impulsiveness. Female patients with BPD were included and compared to age- and sex-matched healthy subjects. Self-rating instruments, such as the State-Trait Anxiety Inventory (STAI), State-Trait Anger Expression Inventory (STAXI), and the Barratt Impulsiveness Scale (BIS) were used to assess clinical scores of anxiety, anger, and impulsiveness. Evoked potentials were recorded following the application of acoustic stimuli with increasing intensities; the LD was analysed using dipole source analysis. The mean LD was significantly higher in patients with BPD compared to controls. In the entire sample there were significant positive correlations of LD with state anxiety scores and STAXI subscores. The data contribute to the knowledge of neurophysiological alterations in patients with BPD, supporting the hypothesis of serotonergic dysregulation in the pathophysiology of the disorder. The significant clinical correlations suggest monoaminergic modulations of psychopathology on the symptom level.

P02-412 - Borderline personality disorder - a dysregulation of the endogenous opioid system?

The neurobiology of borderline personality disorder (BPD) remains unclear. Dysfunctions of several neurobiological systems have been discussed, including serotoninergic, dopaminergic, and other neurotransmitter systems.Here we present a theory that alterations in the sensitivity of opioid receptors or the availability of endogenous opioids constitute part of the underlying pathophysiology of BPD.1 The alarming symptoms and self-destructive behaviors of the affected patients may be explained by uncontrollable and unconscious attempts to stimulate their endogenous opioid system (EOS) and the dopaminergic reward system, regardless of the possible harmful consequences. Neurobiological findings that support this hypothesis are reviewed: Frantic efforts to avoid abandonment, frequent and risky sexual contacts, and attention-seeking behavior may be explained by attempts to make use of the rewarding effects of human attachment mediated by the EOS. Anhedonia and feelings of emptiness may be an expression of reduced activity of the EOS. Patients with BPD tend to abuse substances that target μ-opioid receptors. Self-injury, food-restriction, aggressive behavior, and sensation-seeking may be interpreted as a desperate attempt to artificially set the body to “survival mode”, in order to mobilize the last reserves of the EOS. BPD-associated symptoms, such as substance abuse, anorexia, self-injury, depersonalization, and sexual overstimulation, can be treated successfully with μ-opioid receptor antagonists.An understanding of the neurobiology of BPD may help in developing new treatments for patients with this severe disorder.

Borderline personality disorder: A dysregulation of the endogenous opioid system?

The neurobiology of borderline personality disorder (BPD) remains unclear. Dysfunctions of several neurobiological systems, including serotoninergic, dopaminergic, and other neurotransmitter systems, have been discussed. Here we present a theory that alterations in the sensitivity of opioid receptors or the availability of endogenous opioids constitute part of the underlying pathophysiology of BPD. The alarming symptoms and self-destructive behaviors of the affected patients may be explained by uncontrollable and unconscious attempts to stimulate their endogenous opioid system (EOS) and the dopaminergic reward system, regardless of the possible harmful consequences. Neurobiological findings that support this hypothesis are reviewed: Frantic efforts to avoid abandonment, frequent and risky sexual contacts, and attention-seeking behavior may be explained by attempts to make use of the rewarding effects of human attachment mediated by the EOS. Anhedonia and feelings of emptiness may be an expression of reduced activity of the EOS. Patients with BPD tend to abuse substances that target mu-opioid receptors. Self-injury, food restriction, aggressive behavior, and sensation seeking may be interpreted as desperate attempts to artificially set the body to survival mode in order to mobilize the last reserves of the EOS. BPD-associated symptoms, such as substance abuse, anorexia, self-injury, depersonalization, and sexual overstimulation, can be treated successfully with opioid receptor antagonists. An understanding of the neurobiology of BPD may help in developing new treatments for patients with this severe disorder.

Metabolic Alterations in the Amygdala in Borderline Personality Disorder: A Proton Magnetic Resonance Spectroscopy Study

Emotional dysfunction in a frontolimbic network has been implicated in the pathophysiology of borderline personality disorder (BPD). The amygdala is a key region of the limbic system and plays an important role in impulsivity, affect regulation, and emotional information processing and thus is likely related to BPD symptoms. Alterations of the metabolism in the amygdala might be of interest for understanding the pathophysiology of BPD. However, the amygdala is a difficult region from which to acquire magnetic resonance spectra. We implemented a method for proton magnetic resonance spectroscopy ((1)H MRS) at 3.0 T in which we acquire data within only the small amygdala. The purpose of this study was to determine alterations of the metabolism in the amygdala in BPD patients. Twenty-one unmedicated BPD patients and 20 age-matched healthy control participants underwent (1)H MRS to determine neurometabolite concentrations in the left amygdala. All participants underwent psychometric assessments. Significantly reduced total N-acetylaspartate (tNAA) and total creatine (tCr) concentrations in the left amygdala of patients with BPD were found. BPD patients with comorbid posttraumatic stress disorder (PTSD) showed lower levels of tCr compared with BPD patients without PTSD and healthy control subjects. No significant correlations between neurochemical concentrations and psychometric measures were found. Decreased tNAA and tCr might indicate disturbed affect regulation and emotional information processing in the amygdala of BPD patients. These findings are consistent with many functional and structural neuroimaging studies and may help to explain the greater emotional reactivity of BPD patients.

Editorial: Issues for DSM-V: I) Including Biological Variables To Objectively Comfort the Clinical Diagnosis of Borderline Personality Disorder and II) Proposing a New Subcategory To Be Included in the Criteria Sets for Further Study

Borderline personality disorder (BPD) is a serious chronic condition which may lead to a poor quality of life and carries a considerable risk of comorbidity and suicide. The syndrome has been acknowledged and investigated in psychiatry for at least seventy years. The DSM-IV gives a panel of nine symptoms and manifestations for its diagnosis, but not taking into account neurobiological and objective issues. The issue of whether BPD should be considered as a discrete condition, as the edge of a dimensional state ranging from ‘almost normal’ personalities to clearly pathological ones or as a hybrid of traits and symptomatic behaviors (McGlashan, 2005) seems to be important to correctly diagnose our patients and is a corner stone in the Research Agenda for DSM-V. The pathophysiology of BPD is very important because this is the progress which will probably lead to the development of effective treatments. Several investigators have shown some laboratory and objective clinical fi ndings in BPD as normality in endocrinological dynamic tests (De La Fuente et al., 2002), alterations in sleep-EEG parameters (De la Fuente et al., 2004), disturbed regional brain glucose metabolism (De la Fuente et al., 1997), abnormal scalp EEGs (De la Fuente et al., 1998) and an extremely high prevalence of neurologic soft signs (De la Fuente et al., 2006). These facts probably refl ect common underlying non focal nervous system failure and hypothalamic-pituitary-adrenal axis normality in BPD. However, these fi ndings are not pathognomonic of the condition and BPD is diagnosed according to DSM-IV when a patient shows at least fi ve symptoms out of a list of nine. First & Zimmerman (2006) propose that biological variables can aid to identify the patients as compared to the criteria used now to defi ne them. For this the objective signs and facts found in BPD could be included as diagnostic criteria in the DSM-V. Scalp wake EEG, the clinical exploration for neurologic soft signs, sleep EEG recordings and the two endocrine tests, dexamethasone suppression and TRH stimulation, which are cheap, not invasive and have shown to be linked to the diagnosis of BPD could be incorporated in a diagnostic weighting construct with these variables as additional score items. This would have at least three advantages over the present criteria: fi rstly, a part of the diagnosis of BPD would become objective, secondly, having these parameters would attach physiopathological information to the diagnosis and thirdly, the laboratory information and objective

123I] ADAM and SPECT in patients with borderline personality disorder and healthy control subjects

Background: Impulsive behaviour, a key feature in borderline personality disorder (BPD), is associated with an impairment of the central serotonergic system. We hypothesized that the serotonin transporter availability is altered in patients with BPD and that there is an association between scores of impulsive aggression and serotonin transporter availability. Methods: In a group of eight female patients with BPD and nine healthy female controls, single photon emission computed tomography (SPECT) was conducted by using the serotonin specific radioligand [123I] ADAM. Using an occipital reference region, brain serotonin transporter availability was measured and ratios of specific to nonspecific [123I] ADAM binding for the brainstem and hypothalamus were calculated. Impulsiveness, anger and depressive symptoms were assessed using the Barratt Impulsiveness Scale, the State-Trait Anger Expression Inventory and the Beck Depression Inventory. Results: Mean specific-to-nonspecific ratios showed a 27% higher brainstem and a 29% higher hypothalamus [123I] ADAM binding in BPD patients compared to healthy controls. Significant correlations were found between ADAM binding and age, impulsiveness, and anger, but not depression. Conclusion: Our results are consistent with previous data suggesting a serotonergic dysfunction in the pathophysiology of BPD. Scores of impulsiveness and anger seemed to be associated with serotonin transporter availability in patients and in healthy controls.

The Loudness Dependence of Auditory Evoked Potentials in patients with borderline personality disorder and healthy control subjects

Background: Alterations in the central serotonergic system are considered to be involved in the pathophysiology of the borderline personality disorder (BPD). The loudness dependence of the N1/P2 component of auditory evoked potentials (LD) has been shown to indirectly reflect central serotonergic activity. The aim of this study was to investigate LD in patients with BPD and healthy controls, and to investigate the association between LD and scores of impulsiveness, aggression and anxiety. Methods: Nine female patients with BPD were compared with nine healthy female control subjects. Anger, impulsiveness and anxiety were assessed with the State-Trait Anger Expression Inventory, the Barratt Impulsiveness Scale and the State-Trait Anxiety Inventory. We assessed the LD upon a pseudo-randomized presentation of auditory stimuli of five different loudness intensities. The LD of the relevant subcomponents reflecting the serotonergic activity of the primary auditory cortex (tangential dipol) was investigated using dipole source analysis. Results: The mean LD of the tangential dipole was significantly higher in BPD patients than in healthy controls. Positive correlations between LD and subscores of anger and anxiety were found. Conclusion: Our data are in line with earlier findings of a pronounced loudness dependence of auditory evoked potentials in patients with BPD and support the hypothesis of a serotonergic dysregulation in the pathophysiology of BPD.

A voxel-based morphometric MRI study in female patients with borderline personality disorder

Subtle prefrontal and limbic structural abnormalities have been reported in borderline personality disorder (BPD). In order to further validate the previously reported findings and to more precisely describe the nature of the structural change we performed a voxel-based morphometric (VBM) study in patients with BPD. Twenty female patients with BPD and 21 female healthy controls were investigated. High-resolution 3-D datasets were acquired and analyzed following an optimized protocol of VBM in the framework of statistical parametric mapping (SPM99). Gray matter volume loss was found in the left amygdala. No other differences in gray or white matter volume or density were found anywhere else in the brain. Our findings support the hypothesis that temporolimbic abnormalities play a role in the pathophysiology of BPD. Prefrontal structural alterations in BPD were not observed in this study.

Electrophysiological aberrations in borderline personality disorder: state of the evidence.

Electrophysiological technology is noninvasive and relatively inexpensive. In order to assess the usefulness of this technology in probing the pathophysiology of borderline personality disorder (BPD), we reviewed the literature in which an electrophysiological modality was used to examine BPD. Twenty-two articles were identified, from which diagnostic criteria and data on comorbidity and control groups were extracted. Although the majority of studies pointed to a high prevalence of electrophysiological aberrations in patients, very few studies had adequate control groups and adequate evaluation of comorbidity. We conclude that although the existing literature reflects a preliminary stage of the field, it suggests that electrophysiological investigations may be useful in investigating BPD.

Effects of Carbamazepine on Dexamethasone Suppression and Sleep Electroencephalography in Borderline Personality Disorder

The pathophysiology of borderline personality disorder (BPD) remains obscure, but there is mounting evidence of brain dysfunction without focal abnormality. The dexamethasone suppression test (DST) and sleep electroencephalography (sleep EEG) have been studied in BPD, but the findings seem to be related to a concomitant axis I diagnosis of major depression (MD) rather than to BPD itself. There is no effective treatment for BPD. Carbamazepine (CBZ) has shown contradictory results and in a previous study, our results were negative. In this study, we investigated the effects of CBZ versus placebo on the DST and sleep EEG in a sample of 20 BPD patients without concomitant MD. CBZ given at doses that are therapeutic for epilepsy and affective disorders may have an effect on the DST and sleep EEG in BPD. CBZ significantly increased the postdexamethasone plasma cortisol values. This did not parallel MD or an increase in the Hamilton depression rating scores. CBZ also increased slow wave sleep (SWS). The mechanisms by which CBZ increased postdexamethasone plasma cortisol levels and SWS in BPD are discussed.

Temporal glucose metabolism in borderline personality disorder

The pathophysiology of borderline personality disorder (BPD) is obscure. Underlying organic factors such as epilepsy are suspected because clinical characteristics of the syndrome are similar to some manifestations of patients with complex partial seizures (CPS). Positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) reveals hypometabolism in the area surrounding epileptic foci. To test the epilepsy hypothesis in BPD, we have explored 10 patients with BPD and compared them with 15 control subjects using PET with FDG. We conclude that PET provides no metabolic indication of temporal lobe epilepsy in BPD.

Temporal glucose metabolism in borderline personality disorder

The pathophysiology of borderline personality disorder (BPD) is obscure. Underlying organic factors such as epilepsy are suspected because clinical characteristics of the syndrome are similar to some manifestations of patients with complex partial seizures (CPS). Positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) reveals hypometabolism in the area surrounding epileptic foci. To test the epilepsy hypothesis in BPD, we have explored 10 patients with BPD and compared them with 15 control subjects using PET with FDG. We conclude that PET provides no metabolic indication of temporal lobe epilepsy in BPD.