Understanding Anxiety in Borderline Personality ...

Curr Treat Options Psych DOI 10.1007/s40501-017-0122-0

Personality Disorders (M Goodman, Section Editor)

Understanding Anxiety in Borderline Personality Disorder Andrea Bulbena-Cabre´, M.D., M.Sc1,2,3,* M. Mercedes Perez-Rodriguez, M.D., Ph.D1,2,4 Stephen Porges, Ph.D5,6 Antonio Bulbena, M.D., Ph.D, M.Sc (Cantab)3,4,7 Marianne Goodman, M.D1,2 Address *,1 Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, New York, NY, 10029, USA Email: [email protected] 2 Mental Illness Research Education and Clinical Centers, VA Bronx Health Care System, Bronx, NY, USA 3 Department of Psychiatry and Forensic Medicine (UAB), Autonomous University of Barcelona, Barcelona, Spain 4 Centro de Investigación en Red de Salud Mental, (CIBERSAM), Madrid, Spain 5 Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA 6 Kinsey Institute, Indiana University, Bloomington, IN, USA 7 Mar Health Park, Neuropsychiatry and Drug Addiction Institute (INAD), Barcelona, Spain

* Springer International Publishing AG 2017

This article is part of the Topical Collection on Personality Disorders Keywords Anxiety I Borderline personality disorder I Comorbidity I Neurobiology I Autonomic nervous dysfunction

Opinion Statement There is substantial evidence that borderline personality disorder and anxiety disorders not only co-occur but also mutually influence their outcomes and treatment responses. Both share a significant neurobiological overlap including abnormalities in the limbic system, hypothalamic pituitary adrenal axis, serotoninergic transporter and glucocorticoid transporter genes, and an atypical regulation of the autonomic nervous system. Anxiety should be systematically assessed in patients with borderline personality disorder using dimensional instruments that capture not only the psychological aspects of the disorder but also the bodily and the somatic complaints as they are extremely common in these patients. Little is known about the treatment of this comorbidity but there is some evidence about the effect of antidepressants and some psychotherapies like cognitive or dialectical behavioral therapy, but new non-pharmacological strategies are emerging. Future lines of research should explore the role of new neurobiological treatments like oxytocin, or the emerging field of nutritional psychiatry and the role of the microbiome.

Personality Disorders (M Goodman, Section Editor) Ultimately, more efforts are needed to understand the role of body perception and autonomic dysfunction in this comorbidity, as it could be the key to developing more specific treatment approaches.

Introduction Clinical and neurobiological data suggest that psychiatric disorders as traditionally defined by the Diagnostic Statistical Manual of Mental Disorders 5 (DSM-5) are more comorbid than expected by chance, often share neurobiological features and alterations across multiple brain systems [1•]. In this article, we review the co-occurrence of borderline personality disorder and anxiety and discuss their common neurobiology, the proper assessment of anxiety among borderline patients, current treatment options and future directions. Personality disorders are defined as patterns of inner experience and behavior causing distress and leading to maladaptive functioning in the areas of emotion, cognition, interpersonal relationship, and impulse control. Epidemiological studies have found that the prevalence of borderline personality disorder ranges from 1 to 2% of the general population, but it increases to 10% in psychiatry outpatients and 20% in inpatients [2–4]. These studies also found that, in clinical settings, it is more common in women than in men (about 70 and 30%, respectively), indicating a sex preference. The dominating features of borderline personality disorder are mostly described by four sets of psychopathological symptoms including affective disturbance, disturbed cognition, impulsivity, and intense unstable relationships [5]. Patients suffering from this personality disorder often experience not only a wide range of comorbidities and psychological symptoms but also higher somatic complaints, chronic pain and greater utilization of medical services [6, 7]. This has a major impact on health services, particularly in the frequently occurring situation of crisis, and therefore causes a considerable amount of costs [8].

Anxiety disorders are chronic, disabling and represent the 6th cause of disability worldwide [9]. While they are the most prevalent psychiatric condition among all ages, they are often underdiagnosed and untreated [10]. The estimated lifetime prevalence of any anxiety disorder is around 15% and this has a significant public health impact. The impact is not only explained by the cost of the treatment but rather by the high cost of frequent medical evaluations and treatment of physical manifestations of the disorder [11]. Despite the fact that physical complaints and somatic conditions are very frequent among patients with anxiety, their current nosology characterizes only the psychological aspects of the disorder and neglects the body manifestations, which hinders even more their proper diagnosis. To address this problem, there is increasing research about possible biological markers of anxiety and in the recent years the Joint Hypermobility Syndrome (JHS) has been identified as a marker for a homogenous subgroup of anxiety disorders characterized by increased fears and greater anxiety intensity, and higher somatic and bodily symptoms [12]. Although the JHS-anxiety phenotype has never been studied in borderline personality disorder, it has been observed across several other domains of psychopathology [13, 14]. The underlying mechanisms behind the association between JHS and anxiety include genetic risks, autonomic nervous system dysfunction, increased exteroceptive and interoceptive mechanisms and decreased proprioception [15••]. Recent neuroimaging studies have also shown an increased activation in emotion-processing brain regions [16, 17], which translates into a higher affective reactivity, a clinical feature that overlaps with borderline patients.

Comorbidity The “borderline” term was initially described by the psychoanalyst Adolph Stern (1938) to identify a subgroup of patients that disregarded the usual

Understanding Anxiety in Borderline Personality Disorder

Bulbena-Cabré et al.

Fig. 1. How to approach anxiety in borderline personality disorder. STAI State Trait Anxiety Inventory, BAI Beck Anxiety Inventory, HADS Hospital Anxiety and Depression Scale, BPQ Body Perception Questionnaire, SQ-CH Screening Questionnaire to Detect Hypermobility, CBT Cognitive Behavioral Therapy, BDT dialectical behavioral therapy, SSRIs selective serotonin reuptake inhibitor.

boundaries of psychotherapies, which fell on the border between psychosis and neurosis [18]. However, the borderline construct has undergone several major shifts over the years and the essential features of borderline personality disorder per the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) are a “pervasive pattern of instability of interpersonal relationships, self-image, and affects, and marked impulsivity, beginning in early adulthood and present in a variety of contexts” [19]. While “anxiety” is mentioned in the diagnostic criteria within the affective instability section, it is specified that it “usually lasts a few hours and only rarely more than a few days” and anxiety is categorized as a sporadic set of symptoms rather than a stable trait. However, if we evaluate the core areas of borderline personality disorder psychopathology [5, 20], different features of anxiety, fear reactions (i.e., dissociation) or bodily symptoms are present within those set of symptoms, (see underlined terms below). a. Affective disturbance is described as dysphoric affect, usually experienced as aversive tension, fear, sorrow, shame, guilt and inner emptiness. Intense mood reactivity in the interpersonal realm, with frequently and rapidly changing affective states within 1 day.


b. Disturbed cognition in borderline personality disorder includes three levels of cognitive symptomatology [21]. The first level is defined as troubling non psychotic symptoms such as overvalued experiences, dissociation and depersonalization and derealization. The second and the third level are quasipsychotic and psychotic like experiences respectively. c. Impulsivity is reflected in different modes of more severe less severe selfharm, self-injurious behavior and suicidal behavior in particular, but also as disordered eating or substance abuse. d. Unstable relationship that are dominated by profound fear of abandonment and by unpredictable changes. From a categorical point of view, there is a high comorbidity between anxiety and borderline personality disorder and several studies have shown that they also mutually influence their outcomes. In fact, Goodman et al. found that one of the key borderline personality disorder precursors in early infancy is separation anxiety along with features of unusual sensitivity, and an inability to self-soothe in borderline males [22]. Cross-sectional data shows that comorbid anxiety among borderline patients ranges from 14 to 22% for generalized anxiety disorder (GAD), 2–48% for panic disorder (with and without agoraphobia), and 19–46% for social phobia [23–25]. Studies that were done using versions of the DSM which classified posttraumatic stress disorder (PTSD) and obsessive-compulsive disorder (OCD) as anxiety disorders (e.g., DSM-IV) have also shown high rates of PTSD (25–56%) and OCD (16– 20%) among borderline patients. In addition, high rates of lifetime anxiety disorders have been found in a large-scale community sample of borderline patients [26]. On the other hand, there is also evidence that there is a substantial comorbidity of personality disorders (PD) among patients with anxiety diagnoses. A meta-analysis published by Friborg [27] found that 39% of patients diagnosed with anxiety had cluster CPD, 19% had cluster B-PD and 13% had cluster A-PD. When the authors looked at each specific personality disorder, they found that at least 16% of patients with panic disorder (with and without agoraphobia) and 9% of patients with GAD had comorbid borderline personality disorder. Some studies have evaluated the interaction between borderline personality disorder and anxiety disorders longitudinally. Zanarini et al. [28] found that anxiety comorbidity lengthened borderline personality disorder time to remission. Another study that followed patients for 2 years found that borderline personality disorder improvement predicted PTSD remission [29]. A 7-year follow-up study found that baseline borderline personality disorder status did not predict remission of any anxiety diagnosis (including OCD or PTSD) but did predict increased risk of OCD relapse [30]. The National Epidemiologic Study of Alcohol and Related Conditions found that after 3 years, baseline borderline personality disorder predicted longer time to remission of GAD, social phobia, specific phobia, and panic disorder [31]. Lastly, Keuroghlian et al. [32•] found that borderline personality disorder negatively affects the course of GAD, social phobia, and PTSD. In contrast, none of the anxiety disorders, aside from PTSD, had any effect on the borderline personality disorder course.



Therefore, there is solid evidence that both disorders not only co-occur but also influence their outcomes and time to remission bi-directionally, especially in PTSD and to a lesser extend GAD and the phobic disorders.

Neurobiology Neurobiologically, both anxiety and borderline personality disorder share a significant overlap. Both have abnormalities in the limbic system (specifically in the amygdala), the hypothalamic pituitary adrenal axis, in the serotonin transporter and glucocorticoid receptor genes, and lastly in the autonomic nervous system.

Limbic system—amygdala The limbic system is historically conceptualized as the emotion-processing brain structure. The limbic cortex is part of the phylogenetically ancient cortex and integrates sensory, affective and cognitive components of pain processes and information regarding the internal bodily state [33–35]. The amygdala is a key area of the limbic system and processes emotionally salient stimuli and initiates the appropriate behavioral response. It is responsible for the expression of fear and aggression as well as species-specific defensive behavior [36] and is involved in the generation of negative states [37]. There is robust evidence suggesting that the amygdala is hyperreactive in mood [38], emotional [39], and anxiety disorders [36]. In borderline personality disorder, there is also evidence of decreased gray volume of the left amygdala and right hippocampus [40, 41••] and heightened activation of the left amygdala during processing of negative emotional stimuli. Functional MRI studies have also found heightened activation during processing of negative emotional stimuli in left hippocampus and posterior cingulate cortex as well as diminished activation in prefrontal regions [42]. Although specific anxiety disorders are associated with different brain alterations in the limbic system, amygdala hyperreactivity has been implicated in symptoms of panic disorder [43], social anxiety disorder, PTSD [39], and generalized anxiety disorder [36].

Hypothalamic pituitary adrenal axis (HPA axis) Both anxiety and borderline personality disorder are considered stress-related disorders and share a disruption at different levels of the stress circuits including neurotransmitters, neuropeptides, and neuroendocrine signaling. During acute stress, initial brain responses normally involve increased catecholamine activity (leading to sympathetic nervous arousal) and increased production of cortisol (via the HPA axis) [44]. These neuroendocrine systems, which help individuals cope with stress, are normally well-balanced responses that shut down after stress is dealt with [44]. Several studies have shown that anxiety disorders and borderline personality disorder have abnormalities in the regulation of the HPA system [36, 41••, 44–46].

Genetics Both disorders have a moderate to high degree of heritability [47–50] and are more common in females compared to males. In borderline personality

Personality Disorders (M Goodman, Section Editor) disorder, Gunderson at el. conducted a family study to investigate the degree to which borderline traits clustered within families [51]. They found that the prevalence of borderline personality disorder among relatives of probands with borderline personality disorder was 14.1% compared with 4.9% in the family members of controls. The relative risk that if one family member had borderline personality disorder, so too would another was 3.9 (95% confidence interval, 1.7–9.0) when compared with controls. Heritability in borderline personality disorder PD is also supported by twin studies that estimated that heritability traits in borderline patients are at 35% [52]. In the area of anxiety disorders, there is strong evidence of a substantive familial aggregation in panic disorder, generalized anxiety disorder, phobias, and obsessive-compulsive disorder [53]. Another common genetic finding is the dysfunction of the serotonin receptor genes. In borderline personality disorder, associations with polymorphisms in the serotonin transporter gene, 5HTR2A and 5HTR2C have been described [54]. Different anxiety disorders have different genetic alterations but a variant in the serotonin transporter gen (SERT) has been associated with the pathology of panic disorder, PTSD, social anxiety, and GAD among other anxiety diagnoses [36]. In this sense, the research regarding the consequences of the variation in the promoter region of the serotonin transporter gene (5-HTT) in organisms’ stress responses to their environments [55] could shed light into the common genetic predisposition of this comorbidity [56–58]. Other genes that should be explored are the glucocorticoid receptor gens as they are also found to be affected in both borderline personality disorder and anxiety [56, 59].

Dysfunction of the autonomic nervous system The conceptualization of the autonomic nervous system within the medical field has not kept up-to date with the neurophysiological research expanding our understanding of bidirectional connections between the brain and visceral organs. Evidence from neuroscience and physiological studies of subjective experiences is leading to rapid proliferation of models of embodied experiences that involve afferent and efferent pathways between peripheral systems of the body and central brain networks [60, 61]. The Polyvagal Theory [60, 62–65] has provided a coherent framework for generating hypotheses about the psychophysiological abnormalities that are likely characterize emotional disorders, in which comorbidities manifest in physical health via disruption in feedback (neural regulation) of visceral organs resulting in irritable bowel syndrome or fibromyalgia among others. It is a phylogenetic approach relating the autonomic nervous system to behavior, specifically to prosocial and defensive behaviors. This theory has conceptualized the processes that give rise to individual differences in body awareness and the reactivity of the body to internal and external challenge. In this sense, body awareness can be described as the subjective experience of afferent information arising from within the body and serves as a “sixth sense” that provides information about internal states [66, 67] and is assumed to be an important substrate of emotions, motivation, and self-awareness. Augmented or disordered awareness of such bodily signals is a feature of multiple clinical disorders such as anxiety, panic attacks, and depression, Joint Hypermobility Syndrome, and borderline personality disorder [68, 16, 66, 69, 70].



Recently, research has studied the mechanisms by which emotion dysregulation among borderline patients is reflected in the autonomic nervous system [71]. From the perspective of the Polyvagal theory, the emotional impairment seen different stress-related psychopathologies may be explained by an increased sensitivity to threat information [72]. The increased sensitivity is reflected in decreased vagal control and results in inability to appropriately engage or disengage in defense systems. Atypical vagal influence has been related to multiple emotional disorders including worry [73], self-injury [74], trait hostility [75], stress [76], and borderline personality disorder [71]. However, despite the evidence of the key role of the autonomic nervous systems, clinical research and treatment of both disorders often focuses on mental experiences or brain structures, overlooking the dynamic embodied experiences that are part of affective processes and clinical problems. By monitoring the dynamic regulation of the ANS, we would obtain a measurable intervening variable that may regulate or distort the detection of threat which would be especially significant in these patients.

Assessment Many nosologists have argued that it is better to think of personality disorders along dimensions of psychopathology than categorical entities, especially because the treatment response depends more on dimensions of symptoms rather than diagnostic categories. Dimensional measures of personality disorder are more reliable, stable, and more highly associated with measures of severity than categorical classifications [77, 78]. Therefore, both anxiety and borderline features should be evaluated from a dimensional point of view and most importantly, anxiety symptomatology should always be evaluated in every patient with borderline personality disorder. From an assessment perspective, the first step of selecting an appropriate tool is to decide whether the evaluation shall focus on more generic symptoms of anxiety, which are common in most anxiety disorders, or more specific symptoms of one particular anxiety disorder. In this paper, we focus on tools that assess anxiety symptoms from a general perspective rather than on instruments that measure a specific anxiety disorder. The most prominent and widely used instruments to assess anxiety are the State Trait anxiety inventory (STAI) [79], the Hospital Anxiety and Depression Scale [80] (HADS), or the Beck Anxiety Inventory (BAI) [81]. They all have good psychometric properties and have norm data available [82]. While the STAI differentiates trait and state anxiety, the HADS offers information about the severity of depression and anxiety but there is evidence of reduced validity in elderly populations [83]. The BAI focus on somatic aspects of anxiety which is crucial for the appropriate assessment of anxiety symptomatology; however, it may overrate anxiety in medical conditions [82]. Since somatic complaints of anxiety are usually underdiagnosed, other scales that evaluate this such as the “Clinical Anxiety Scale” [84, 85] or the Zung Anxiety Scale [86] are also appropriate despite their limited use. As stated above, both patients with borderline personality disorder and anxiety often suffer from an atypical regulation of the autonomic nervous system and abnormal body perception which may be cause several bodily

Personality Disorders (M Goodman, Section Editor) manifestations. Following the Polyvagal Theory, Porges created the “Body Perception Questionnaire” (BPQ) [87], which assesses subjective experiences of body awareness and autonomic reactivity. The BPQ has been used in several peer review studies to quantify subjective reports of bodily reactions and states. Since autonomic dysfunction and abnormal body perception have been hypothesized to be the key feature of the phenotype JHS-anxiety, assessing this phenotype among borderline patients is warranted. The Screening Questionnaire to detect Hypermobility (SQ-CH) is a validated self-assessment instrument that measures the JHS including articular and extra-articular symptoms and has good reliability and validity [88]. By obtaining this information, the clinician may obtain finer-grained information about the anxiety phenotype which can translate into more specific interventions so clinicians should include those instruments in their standard practice.

Treatment options Over the last two decades, significant progress has been made in the area of treatment of borderline personality disorder and anxiety disorders separately. For both disorders, current accepted interventions include psychosocial and psychopharmacological approaches. However, the study of anxiety treatment in borderline personality disorder is limited by the small number of studies available and the exclusion of patients with severe borderline features in those studies [89]. a. Psychosocial interventions: For anxiety disorders, there is strong evidence that Cognitive Behavioral Therapy (CBT) is effective and the response rates are about 60–90%. CBT, particularly when it includes an exposure component [11, 90], is an empirically supported psychosocial treatment for anxiety disorders that has been shown to be highly efficacious, desirable to patients, and cost-effective [91, 92]. Several randomized controlled trials examined the effects of several psychosocial treatments in borderline personality disorder using different outcome measures such as anxiety. Most of those studies found significant reduction of anxiety most commonly with Dialectical Behavioral Therapy (DBT) but also with Psychoanalytically Oriented Therapy, Interpersonal Psychotherapy, CBT and Emotion regulation group therapy [93–100]. A recent meta-analysis found that among all the specialized therapies, both the Dialectical Behavior Therapy and psychodynamic approaches, are effective for borderline symptoms and related problems such as anxiety. Nonetheless, effects are small, inflated by risk of bias and publication bias, and particularly unstable at follow-up [101] so more research is needed in this field. However, if there is evidence of atypical body perception or positive screen for JHS, the clinician should consider addressing emotions that are frequently associated with those problems such as chronic pain, negative feeling and poor emoticon regulation [16].

b. Pharmacotherapy: No class of psychopharmacological agent appears to improve borderline personality disorder in general but medication is given to target the dominating symptomatology of the individual such as impulsivity, anxiety or emotional dysregulation [8]. A Cochrane review found that borderline patients may obtain some beneficial effects with second



generation antipsychotics, mood stabilizers, and dietary supplementation by omega-3 fatty acids [102]. On the other hand, no promising results are available for the core borderline symptoms of chronic feelings of emptiness, identity disturbance or abandonment. While antidepressants are not widely supported to treat the main borderline traits, they are especially helpful in the presence of comorbid conditions like anxiety. In this sense, the selective Serotonin Reuptake inhibitors (SSRIs) are best known to influence emotional dysregulation in borderline personality disorder [8] and are effective for anxiety. The second large group of medications to treat anxiety disorders is benzodiazepines but they are strongly discouraged in patients with personality disorders. They can lead to cognitive and motor impairment, excessive sedation and may interact negatively with some forms of psychotherapy [8]. They can also cause paradoxical disinhibition which could worsen the impulsivity in borderline personality disorder [103]. Besides this, personality disorders are chronic conditions and the risk of psychological and physical dependency may be higher than in other disorders. Other types of experimental treatments for some specific types of anxiety disorders such as OCD, agoraphobia and social anxiety disorder include the combination of an SSRIs with a second generation antipsychotic although the evidence is scarce [11]. GABAergic antiepileptics, such as gabapentin, pregabalin, and tiagabalin among others, are also showing some promising response for some anxiety disorders [104, 105].

c. Other non-pharmacological strategies have been examined as treatment for anxiety but to date no reliable information is available to treat these symptoms in borderline personality disorder. Some studies found that deep brain stimulation in the nucleous accumbens is especially effective for OCD and other anxiety disorders [106]. The repetitive transcranial magnetic stimulation (rTMS) is a noninvasive mean of stimulating the cerebral cortex and therapeutically has shown promising results in the area of treatment resistant depression [107]. In the area of anxiety disorders, rTMS has been effective in treating OCD [108] and GAD although the evidence is mixed and limited [109–111]. Another option that should be considered, especially in patients with JHS and/or atypical body perception profiles, would be interventions that address mind-body interactions. Literature confirms a positive therapeutic outcome for some meditative therapies such as meditation, Yoga and mindfulness training among others [112].

Future directions Despite both disorders are very common, there is limited knowledge about their etiologies or their exact pathophysiological mechanisms. Current research supports a substantial neurobiological overlap and this could help develop more specific treatments that act directly on the common affected regions or circuits. In this sense, oxytocin has shown some promising results not only for the treatment of social cognition [113] and attachment modulation in borderline patients [114–117] but also as a treatment for anxiety due to its anxiogenic effects [118], so this area should be further explored in subsequent studies.

Personality Disorders (M Goodman, Section Editor) The field of nutritional psychiatry [119] may also provide common grounds between borderline personality disorder and anxiety disorders because in both disorders, the Autonomic Nervous System (ANS) is much involved. Thus, the incipient role of the microbiome in neuropsychiatric conditions appears to be mediated through the ANS nerves and the ascending vagus nerve [120]. The cholinergic system has been proven to have an important role in behavioral inhibition [121] and autonomic regulation, especially through vagal pathways. In the Hordaland Health Study [122], they found a correlation between anxiety and the nutrient Choline, a B-like vitamin very similar to folate, which is used in the methylation cycle. Patients that were in the lowest percentile of choline consumption had about 33% higher risk of having anxiety disorder. Interestingly, borderline subjects show less choline in hippocampal regions [123] and therefore this field should be explored when further evaluating this comorbidity. Another nutritional supplement that needs to be explored is omega-3 fatty acid, which has been effective in treating features of borderline personality disorder [102], as well as mood and anxiety disorders [124]. Finally, body perception, an often neglected are of psychopathology, may offer some commonalities between anxiety and borderline personality disorder. The well-known so-called pain paradox among borderline subjects [125], by which these subjects might be oversensitive but also hyposensitive to body pain, may be related to the self-injurious behavior seen in these patients. Patients with anxiety have also been found to suffer from an enhanced sensorial sensitivity [126] and therefore, this common ground between these two disorders should be further explored.

Conclusion Despite the overwhelming evidence regarding the common co-occurrence of anxiety and borderline personality disorder, little is known about the appropriate assessment and treatment of anxiety among borderline patients. Borderline patient should be screened for anxiety symptomatology and treat symptoms accordingly, including body symptoms and somatic complaints. Research points towards a significant neurobiological overlap in several systems but among all them, the autonomic nervous dysfunction is the most understudied and more efforts should be made to understand its role in this comorbidity. Future studies should explore new biological therapies such as oxytocin and expand the field of nutritional psychiatry.

Compliance with Ethical Standards Conflict of Interest Dr. Andrea Bulbena-Cabré declares that she has no conflict of interest. Dr. M. Mercedes Perez-Rodriguez declares that she has no conflict of interest. Prof. Stephen Porges declares that he has no conflict of interest. Prof. Antonio Bulbena declares that he has no conflict of interest. Prof. Marianne Goodman declares that she has no conflict of interest.



Human and Animal Rights and Informed Consent All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).

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