Neurobiology Of Borderline Personality Disorder Research Articles

Update on the Neurobiology of Borderline Personality Disorder: A Review of Structural, Resting-State and Task-Based Brain Imaging Studies.

This review summarizes recent advances in research on the neurobiology of borderline personality disorder (BPD) according to structural brain imaging investigations and resting-state and task-based functional brain activation studies. Extending established findings on differences in regional brain volumes and cortical thickness between BPD and healthy controls, recent research illuminates shared and distinct brain structural characteristics compared to other psychiatric diagnoses, and uncovers relations of these brain structures with transdiagnostic symptoms and clinical features. Resting-state functional brain imaging studies reveal disruptions among adolescents and adults with BPD in frontolimbic and default-mode networks, which primarily underlie affect regulation and self-referential processes, respectively. Recent task-based functional brain imaging research builds on existing neurobiological understanding of emotion and cognition in BPD by revealing novel intersections with interpersonal- and stress-related processes. Studies of psychological and pharmacological interventions suggest possible effects on neural regions underlying emotion processing and behavioral control.

Spotlight on borderline personality disorder: History, genetics, and neurobiology

One of my friends is a neuroscientist, and not long ago I met some of her other neuroscientist friends. Interesting conversations begin when a psychiatrist and neuroscientist connect, and among those conversations was one about the history, genetics, and neurobiology of borderline personality disorder (BPD).

Neural Changes in Borderline Personality Disorder After Dialectical Behavior Therapy–A Review

The biological component of the biosocial theory of emotion regulation stipulates that borderline personality disorder (BPD) arises from biological vulnerabilities to heightened emotional reactivity. Comprehensive reviews have consistently implicated abnormalities in the amygdala, anterior cingulate cortex, and hippocampus in the neurobiology of BPD. While Dialectical Behavior Therapy (DBT) is the leading evidence-based psychotherapy for the treatment of BPD, there remains a paucity of literature examining changes in the neurobiology of BPD following DBT treatment. Nine studies were identified that examined neurobiological changes in BPD after the completion of DBT. Results indicated that there was significant deactivation of amygdala activity as well as the anterior cingulate cortex in patients with BPD after DBT treatment. As well, several studies found after DBT treatment, BPD patients had a decreased activity in the inferior frontal gyrus in response to arousing stimuli and increased activity in response to inhibitory control. Future research on the neurobiological change after DBT treatment can help clarify biological mechanisms of change in BPD.

Olfactory sulcus morphology in teenagers with first-presentation borderline personality disorder

Gray matter reduction of the orbitofrontal cortex (OFC) has been reported in borderline personality disorder (BPD), but it remains unknown whether the BPD patients exhibit morphologic changes of the olfactory sulcus, a potential marker of forebrain development located on the OFC. We used magnetic resonance imaging to investigate the length and depth of the olfactory sulcus in 20 teenagers (15 females and 5 males) with first-presentation BPD and 20 healthy controls (15 females and 5 males). While there was no group difference in the length of the sulcus, the BPD patients (especially those with a history of trauma) had a significantly shallower right olfactory sulcus compared with controls. In addition, sulcus depth was negatively correlated with the severity of impulsivity and affective instability in the BPD patients. These preliminary findings may suggest a significant role of environmental risk factors (i.e., trauma exposure) during childhood to adolescence in the neurobiology of BPD.

A Neurobiological Model of Borderline Personality Disorder: Systematic and Integrative Review

Borderline personality disorder (BPD) is a severe mental disorder with a multifactorial etiology. The development and maintenance of BPD is sustained by diverse neurobiological factors that contribute to the disorder's complex clinical phenotype. These factors may be identified using a range of techniques to probe alterations in brain systems that underlie BPD. We systematically searched the scientific literature for empirical studies on the neurobiology of BPD, identifying 146 articles in three broad research areas: neuroendocrinology and biological specimens; structural neuroimaging; and functional neuroimaging. We consolidate the results of these studies and provide an integrative model that attempts to incorporate the heterogeneous findings. The model specifies interactions among endogenous stress hormones, neurometabolism, and brain structures and circuits involved in emotion and cognition. The role of the amygdala in BPD is expanded to consider its functions in coordinating the brain's dynamic evaluation of the relevance of emotional stimuli in the context of an individual's goals and motivations. Future directions for neurobiological research on BPD are discussed, including implications for the Research Domain Criteria framework, accelerating genetics research by incorporating endophenotypes and gene × environment interactions, and exploring novel applications of neuroscience findings to treatment research.

A systematic review of the neurobiological underpinnings of borderline personality disorder (BPD) in childhood and adolescence.

Contemporary theories for the aetiology of borderline personality disorder (BPD) take a lifespan approach asserting that inborn biological predisposition is potentiated across development by environmental risk factors. In this review, we present and critically evaluate evidence on the neurobiology of BPD in childhood and adolescence, compare this evidence to the adult literature, and contextualise within a neurodevelopmental framework. A systematic review was conducted to identify studies examining the neurobiological (i.e. genetic, structural neuroimaging, neurophysiological, and neuropsychological) correlates of BPD symptoms in children and adolescents aged 19 years or under. We identified, quality assessed, and narratively summarised 34 studies published between 1980 and June 2016. Similar to findings in adult populations, twin studies indicated moderate to high levels of heritability of BPD, and there was some evidence for gene-environment interactions. Also consistent with adult reports is that some adolescents with BPD demonstrated structural (grey and white matter) alterations in frontolimbic regions and neuropsychological abnormalities (i.e. reduced executive function and disturbances in social cognition). These findings suggest that neurobiological abnormalities observed in adult BPD may not solely be the consequence of chronic morbidity or prolonged medication use. They also provide tentative support for neurodevelopmental theories of BPD by demonstrating that neurobiological markers may be observed from childhood onwards and interact with environmental factors to increase risk of BPD in young populations. Prospective studies with a range of repeated measures are now required to elucidate the temporal unfurling of neurobiological features and further delineate the complex pathways to BPD.

On the role of oxytocin in borderline personality disorder.

Interpersonal dysfunction is central to borderline personality disorder (BPD). Recent research has focused on the role of oxytocin (OT) in BPD, particularly regarding associations of OT activity with symptoms, genetic polymorphisms of the oxytocin receptor coding gene (OXTR) in BPD, and experimental modification of interpersonal core problems of patients with BPD such as hypervigilance towards threat detection, mistrust, and non-verbal behaviour during social interaction by intranasal application of OT. A literature ('medline') review was performed using the keywords 'oxytocin' and 'borderline personality disorder'. Secondary literature on trauma and attachment in relation to OT was also considered relevant. Together, findings suggest that in BPD OT is associated with enhanced defensive mechanisms and avoidance behaviour. Moreover, gene-environment interaction concerning polymorphic variations of the OXTR gene and childhood adversity in BPD suggests that these genes convey developmental flexibility or 'differential susceptibility' to environmental contingencies, whereby BPD resides at the poor outcome end of the spectrum. In view of the conflicting literature, it needs to be studied carefully whether OT can serve as a therapeutic agent given adjunct to psychotherapy in BPD. More research about the role of OT is also required with regard to the prevention of the non-genetic intergenerational transmission of BPD. Clarifying the role of OT in BPD may also benefit from research in non-human animals targeting the interaction between early adversity and OT availability more directly. The study of oxytocin can contribute to the understanding of the neurobiology of borderline personality disorder. Oxytocin is critically involved in attachment security, and methylation of the oxytocin receptor may play a role in the epigenetic modulation of early adversity. The intranasal application of oxytocin may be a useful therapeutic adjunct to psychotherapy. Insecure attachment and childhood adversity may produce differential neurobiological effects on the oxytocinergic system in borderline personality disorder. There is insufficient knowledge of how oxytocin interacts with vasopressin, testosterone, dopamine, and serotonin, which are also important key players in the experience of social reward and stress responsivity. It is unclear whether or not oxytocin could be beneficial in preventing the intergenerational (non-genetic) transmission of borderline personality traits.

Possible role of a dysregulation of the endogenous opioid system in antisocial personality disorder.

Around half the inmates in prison institutions have antisocial personality disorder (ASPD). A recent theory has proposed that a dysfunction of the endogenous opioid system (EOS) underlies the neurobiology of borderline personality disorder (BPD). In the present theoretical paper, based on a comprehensive database and hand search of the relevant literature, this hypothesis is extended to ASPD, which may be the predominant expression of EOS dysfunction in men, while the same pathology underlies BPD in women. According to evidence from human and animal studies, the problematic behaviours of persons with antisocial, callous, or psychopathic traits may be seen as desperate, unconscious attempts to stimulate their deficient EOS, which plays a key role in brain reward circuits. If the needs of this system are not being met, the affected persons experience dysphoric mood, discomfort, or irritability, and strive to increase binding of endogenous opioids to receptors by using the rewarding effects of aggression by exertion of physical or manipulative power on others, by abusing alcohol or substances that have the reward system as target, by creating an "endorphin rush" by self-harm, by increasing the frequency of their sexual contacts, or by impulsive actions and sensation seeking. Symptoms associated with ASPD can be treated with opioid antagonists like naltrexone, naloxone, or nalmefene.

Improvement of Borderline Personality Disorder with Naltrexone: Results of a Retrospective Evaluation

Introduction Although 85% of inpatients with Borderline Personality Disorder (BPD) receive psychotropic drug treatment, no drug is approved for this indication so far. A dysregulation of the endogenous opioid system (EOS) has been posed to underly the neurobiology of BPD. Accordingly, the opioid antagonist naltrexone might be helpful to treat symptoms of BPD. Two small studies showed limited differences of naltrexone vs. placebo on dissociation, which were not significant, perhaps due to the low power of the studies: Aims and Objectives Naltrexone was administered in treatment-refractory patients with BPD in a university department of psychiatry. This study aimed to assess the relative contribution of naltrexone and other psychopharmacological drugs to the improvement of overall symptomatology in patients with BPD. Methods A retrospective analysis of the charts of inpatients (n=161) with BPD was performed. Patients were classified as either treatment responders or non-responders. As all patients received multiple psychopharmacological treatments, stepwise logistic regression analysis was performed to detect, which drug contributed most to improvement of symptomatology. Results None of the drugs applied contributed significantly to improvement, with the exception of naltrexone (odds ratio, p=2,9) Patients treated with naltrexone (n=55, 34,16%) recovered significantly more often and faster and, in particular, showed highly significant reduction of self-harm and suicidal thoughts. Higher doses of naltrexone treatment were more effective than low-dose treatment; however, the latter was still better than any other treatment. Conclusion Large-scale double-blind studies are warranted to examine the efficacy of opioid antagonists (naltrexone, nalmefene) in BPD.

Depression in patients with borderline personality disorder.

Borderline personality disorder (BPD) and major depressive disorder (MDD) commonly co-occur, but the relationship between these disorders remains unclear. While BPD patients often suffer from depression, their subjective experience and treatment response are different from that experienced by MDD patients without BPD. Surveying the current literature on the interface of these two pathologies, we find that depression in BPD has distinct symptoms, treatment responses, remission predictors, and suicide risks. It tends to be subjectively more severe, more interpersonally fueled, and more persistent than MDD without BPD. BPD depression responds less well to biological treatments and may be fueled by the neurobiology of BPD. These findings suggest that clinicians should recognize the unique features of BPD depression and anticipate a clinical trajectory that may be different from MDD without BPD, keeping in mind that BPD depression tends not to improve until BPD improves.

Complex PTSD, affect dysregulation, and borderline personality disorder.

Complex PTSD (cPTSD) was formulated to include, in addition to the core PTSD symptoms, dysregulation in three psychobiological areas: (1) emotion processing, (2) self-organization (including bodily integrity), and (3) relational security. The overlap of diagnostic criteria for cPTSD and borderline personality disorder (BPD) raises questions about the scientific integrity and clinical utility of the cPTSD construct/diagnosis, as well as opportunities to achieve an increasingly nuanced understanding of the role of psychological trauma in BPD. We review clinical and scientific findings regarding comorbidity, clinical phenomenology and neurobiology of BPD, PTSD, and cPTSD, and the role of traumatic victimization (in general and specific to primary caregivers), dissociation, and affect dysregulation. Findings suggest that BPD may involve heterogeneity related to psychological trauma that includes, but extends beyond, comorbidity with PTSD and potentially involves childhood victimization-related dissociation and affect dysregulation consistent with cPTSD. Although BPD and cPTSD overlap substantially, it is unwarranted to conceptualize cPTSD either as a replacement for BPD, or simply as a sub-type of BPD. We conclude with implications for clinical practice and scientific research based on a better differentiated view of cPTSD, BPD and PTSD.

Neurobiology of borderline personality disorder (BPD) and antisocial personality disorder (APD)

Neurobiology of borderline personality disorder (BPD) and antisocial personality disorder (APD)

P-937 - Borderline Personality Disorder: genetics, neurobiology and development

Introduction Borderline Personality Disorder (BPD) is a common psychiatric disorder and the most frequent personality disorders. Objectives To review the scientific literature and search for features of psychobiological disposition to BPD in childhood and the influence of parental educative strategies on the development of this personality disorder; to review the scientific advances on heritability and neurobiology of BPD. Methods Using Pubmed, we have searched for research and review articles published in the last ten years. The keywords were: borderline personality disorder and genetics, neurobiology and development. Results We have obtained 23 related articles. Conclusion There is supporting evidence that the preborderline child has a genetically based hypersensitivity to interpersonal interactions that interacts with adverse early caretaking experiences and later stressors to become elaborated into disorganized and controlling interpersonal strategies. These interpersonal strategies then provide the soil from which the borderline patient's prototypically contradictory interpersonal features arise.

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.

Is borderline personality disorder part of the bipolar spectrum?

In recent years, advances in the areas of both bipolar and borderline personality disorders have generated considerable interest in the clinical interface between these two conditions. Developments in the study of the neurobiology of borderline personality disorder suggest that many patients with this diagnosis have etiological features in common with those diagnosed with bipolar disorders. This claim is supported by new insights into the phenomenology of both disorders and by evidence that mood stabilizers are efficacious in the pharmacological management of borderline patients. This area of research is an important one because of the considerable morbidity and public health costs associated with borderline personality disorder. Since borderline patients can be so challenging to care for, it may be that a reframing of the disorder as belonging to the broad clinical spectrum of bipolar disorders holds benefits for patients and clinicians alike.

Borderline personality disorder: impaired visual perception and working memory

The neurobiology of borderline personality disorder (BPD) is still elusive. There are a few studies on neuropsychological performance in BPD, which report a broad spectrum of abnormalities. The present study evaluates perception and working memory as instances of basic cognitive functions. Female subjects diagnosed with DSM-IV borderline personality disorder ( n=22) were compared with age- and education-matched controls ( n=25). Perception speed was assessed by a backward masking paradigm. Working memory was tested by a series of delayed matching-to-sample paradigms involving varying subsidiary functions like mental rotation, retrieval from memory, ignoring distracters, and cross-modal performance. In backward masking, BPD subjects required significantly longer stimulus onset asynchrony (SOA) than controls to identify the visual target, and there was an additional slowing of the motor response. Working memory accuracy was impaired in BPD subjects, but did not worsen when the cognitive load was increased. With increasing task difficulty, they traded off speed for accuracy similarly as the controls. Impulsivity and dissociation ratings were not correlated with performance. It is concluded that perceptional speed and working memory are impaired in BPD, but that the deficits are not augmented by increasing cognitive load.

New developments in the neurobiology of borderline personality disorder.

Within the past several years, research on the clinical phenomena and neurobiology of borderline personality disorder has increased substantially. Borderline personality disorder is currently best thought of in terms of dimensions rather than as a categorical disorder. This article reviews the most recent findings on two of the core dimensions--affective dysregulation and impulsivity. Most of the neuropsychologic, physiologic, endocrinologic, and neuroimaging data support the theory that a dual brain pathology, affecting prefrontal and limbic circuits, may underlie this hyperarousal-dyscontrol syndrome.

The Neurobiology of Borderline Personality Disorder: The Synergy of “Nature and Nurture”

The author reviews the current state of our knowledge concerning the neurobiology of borderline personality disorder (BPD). A converging body of scientific evidence indicates that patients with BPD suffer from impairments in the brain systems that regulate impulsivity, aggression, and affect. This article reviews data on the neurobiology of the symptoms of BPD, including emotional and behavioral dysregulation, identity disturbance, cognitive impairments, and interpersonal difficulties. The author first considers the evolutionary context in which BPD can develop to put the neurobiological findings in perspective, and then discusses the roles of both genetic inheritance and the environment in the development of BPD. The role of neurotransmitter systems in the development of impulsive-aggression and affective instability is reviewed. Possible neurobiological contributors to the identity disturbance seen in BPD are also described. The author then considers environmental contributions to BPD and discusses the synergy of nature and nurture in the development of BPD symptoms. Findings concerning the types of neurobiological impairments that can arise as a result of childhood neglect and abuse and other types of chronic severe stress and trauma are discussed. Finally, the author reviews studies of animal attachment models that suggest that types of maternal care can produce lifelong behavioral and physiological differences in offspring and that this effect is mediated through the regulation of gene expression. The author suggests that the large body of neuroscience research reviewed in this article suggests that, while patients with BPD may be born with innate genetic tendencies for impaired brain systems for regulating impulses and affect, the environment they find themselves born into may be critical in determining whether or not they develop the full blown syndrome of BPD.