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Abstract

Progress in understanding borderline personality disorder has unfolded in the last decade, landing in a new COVID-19–influenced world. Borderline personality disorder is now firmly established as a valid diagnosis, distinct from its co-occurring mood, anxiety, trauma-related, and behavioral disorders. Further, it is also understood as a reflection of general personality dysfunction, capturing essential features shared among all personality disorders. Neuroimaging research, representing the vast neurobiological advances made in the last decade, illustrates that the disorder shares frontolimbic dysfunction with many psychiatric diagnoses but has a distinct signature of interpersonal and emotional hypersensitivity. This signature is the conceptual basis of the psychotherapies and clinical management approaches proven effective for the disorder. Medications remain adjunctive and are contraindicated by some guidelines internationally. Less invasive brain-based therapeutics show promise. The most significant change in the treatment landscape is a focus on briefer, less intensive formats of generalist management. Shorter variants of therapies, such as dialectical behavior therapy and mentalization-based treatment, are in the process of being shown to be adequately effective. Earlier intervention and greater emphasis on functional improvement are needed to more effectively curb the disabilities and risks of borderline personality disorder for patients and their families. Remote interventions show promise in broadening access to care.
Over five decades, there has been steady progress in defining the boundaries around borderline personality disorder, discriminating it from other major psychiatric disease categories, delineating its naturalistic course, identifying its biological features, and developing specific interventions proven for its treatment. Although stigma continues, an empirical foundation guiding effective clinical management has been established. New challenges have emerged. This review will provide a clinically relevant summary of the last decade of progress and controversy since our prior review (1).
Every health professional will encounter patients with borderline personality disorder. The good news is its prognosis has transformed from one of therapeutic nihilism to one of realistic optimism, especially with the advent of multiple evidence-based treatments (2). But grave concerns remain. The disorder is a significant risk factor not only for repeated life-threatening self-injurious problems, but also for other psychiatric disorders, medical illness, disability, violent crime, and victimization (3, 4); 5%–10% of patients with borderline personality disorder die by suicide (5). Missed or delayed diagnosis is pervasive, limiting appropriate care and resulting in repeated emergency room visits, inpatient admissions, and polypharmacy (610). Access to effective treatment, such as dialectical behavior therapy (DBT) or mentalization-based treatment (MBT), is limited by the intensive, lengthy format of these therapies, which requires training far outside the norm for most training programs for health care providers (11). With high dropout rates approaching 30%, and treatment nonresponse rates estimated at over 40%, patients with borderline personality disorder will frequently lack adequate readiness or conditions to respond to specialized treatment (12, 13). Therefore, all clinical professionals need a credible foundation for providing sound care.
Our understanding of underlying mechanisms, transdiagnostic features shared with co-occurring disorders, and targets for biological interventions has matured. Research efforts aim to refine existing treatment options. Understanding what works for whom, when, and where has sharpened our reconceptualization of steps of care for this disabling, and sometimes fatal, disorder to replace our prior one-size-fits-all attitude toward care. This review will provide updates on basic facts, current controversies in diagnosis, neurobiological advances, and clinical developments to aid health professionals in understanding and treating patients experiencing borderline personality disorder.

Basic Facts: Definitions, Epidemiology, Longitudinal Course

Disturbances in managing emotion, behavior, interpersonal relatedness, and identity define the four quadrants of borderline personality disorder symptoms. These symptoms destabilize major domains of functioning, which cascade into interruption of developmental trajectories and life opportunities, as well as pathways toward poor overall physical and mental health. The disorder affects 1%–3% of the general adolescent and adult population (14, 15). Most health care professionals will encounter patients with the disorder because these patients are overrepresented in acute settings, accounting for 9% of all emergency department visits, 50% of suicidal patients in emergency rooms, and 20%–25% of psychiatric inpatients (710). Almost three-quarters of this population will engage in an average of three suicide attempts in their lifetime (16), and one in 10–20 patients will die from suicide (35). Identity disturbance, frantic efforts to avoid abandonment, and feelings of emptiness predict suicide attempts (3); however, these cardinal features of the disorder are not part of routine assessment in the evaluation of suicidal patients.
Although borderline personality disorder is typically first diagnosed in adulthood, its evolution begins early. Negative emotionality and impulsivity predict harsh parenting styles, which in turn, potentiate risk for later diagnosis of the disorder in the presence of exposure to other social adversities, such as bullying (17, 18). Community-based prospective studies trace fluctuations in borderline personality disorder symptoms starting in childhood, peaking in adolescence, and normatively declining in early adulthood (19). Youths with higher levels of symptoms are at increased risk for retaining the diagnosis and developing other psychiatric disorders in adulthood (20, 21). They are more likely to experience significant social and functional impairment, with lower academic and occupational achievement, higher use of medical and psychiatric services, and less stable social support, even when symptoms decline (22, 23). Early identification of those at-risk can curb this trajectory. However, a widespread myth that the disorder cannot be diagnosed among those younger than age 18 dominates practice, contrary to criteria published as early as in the DSM-III and growing evidence verifying validity of the diagnosis in adolescence (22, 23).
Remission among adults with borderline personality disorder is common, with low rates of relapse (24, 25) (Figure 1). However, recovery (i.e., remission plus having full-time work or study and at least one emotionally sustaining relationship outside family), is more unstable (24, 25). The McLean Study of Adult Development (25) reported that virtually all (99%) participants with borderline personality disorder had achieved at least 2 years of remission by the 16-year follow up, with approximately one-third experiencing relapse, 78% attaining 8 years of remission, and only 10% relapsing. Sixty percent had achieved 2 years of recovery, but nearly half had lost it, demonstrating greater instability of recovery compared with remission. The Collaborative Longitudinal Study of Personality (CLPS) (24, 26) also found remission in 85% and low rates of relapse, but also more limited gains in functional recovery across 10 years. Lower Global Assessment of Functioning scores and more borderline personality disorder criteria met at baseline predicted worse outcomes, whereas good functioning, lower level of borderline or other personality disorder traits, and absence of major depressive disorder predicted remission (26, 27).
FIGURE 1. Longitudinal course of borderline personality disordera
aSummarized from the McLean Study of Adult Development (25) and the Collaborative Longitudinal Personality Disorders Study (24).
These studies have also revealed elevated treatment use, complex psychiatric and medical comorbidity, functional impairment, and ongoing suicide risk among patients with borderline personality disorder compared with those with major depressive disorder or other personality disorders (3, 4, 2832). Costs to society related to borderline personality disorder exceed that of most psychiatric conditions, including depression and anxiety disorders, and are comparable with those of schizophrenia (10). Symptoms manifesting in adolescence increase risk of later unemployment 22-fold and of later disability 15-fold, contributing to high indirect societal costs (3337) (Table 1).
TABLE 1. Borderline personality disorder: basic facts and toolsa
Variable or assessmentMeasure or population
Epidemiology % in adults (% in adolescents) (14, 15, 23, 32) 
 General population2.7% (1%–3%)
 Psychiatric inpatients20%–25% (33%–49%)
 Psychiatric outpatients8%–18% (11%–22%)
 Emergency room visits with suicidal ideation56% (88%)
Suicidal behavior (3, 5, 16) 
 Average number of attempts3
 Suicide3%–10% (50×greater than among general population)
 Proportion of all suicides with borderline personality disorder18% of all suicides; 33% of all youth suicides
Cost to society (10, 33) 
 Indirect costs of lost productivity (Europe)$12,484–$50,000
 Risk for disability with borderline personality symptoms<1915-fold
 Risk for unemployment with borderline personality symptoms<1922-fold
Psychosocial functioning (2437) 
 Functional impairment and changes in symptom levelsGood premorbid function provides positive prognosis; remission predicts good functioning
 Poorer interpersonal functioningImprovement in close relationships occurs with reduction in borderline personality disorder symptoms
Assessments 
 Semi-structured interviews or clinician rated 
  Structured Clinical Interview for DSM-5 Personality DisordersAll personality disorders
  Diagnostic Interview for DSM-IV Personality DisordersAll personality disorders
  International Personality Disorders ExaminationAll personality disorders in DSM-IV and ICD-10
  Revised Diagnostic Interview for BorderlinesBorderline personality disorder only
Diagnostic self-reports 
 Personality Diagnostic Questionnaire-4All personality disorders
 Personality Assessment InventoryAll personality disorders
 Borderline Symptom ListBorderline personality disorder only
 Five-Factor Borderline InventoryBorderline personality disorder only
Screening self-reports for borderline personality disorder 
 McLean Screening Instrument for borderline personality disorder 
 Borderline Personality Questionnaire 
 Zanarini Rating Scale for BPD 
Dimensional personality functioning assessment 
 Personality Inventory for DSM-5Personality traits
 Level of Personality Functioning Scale Self-ReportPersonality functioning
a
From Tomko et al. (14), Kaess et al. (15), Choi-Kain and Sharp (23), and Gunderson et al. (32).
Longitudinal studies have also elucidated the interactive course of borderline personality disorder with common co-occurring disorders. Borderline personality disorder is associated with complex patterns of comorbidity and ongoing vulnerability for poor mental health (34). The majority of individuals with the disorder in CLPS also met criteria for depression, with longer time to remission from and shorter time to relapse to a major depressive episode (35). In contrast, bipolar disorder co-occurred with borderline personality disorder in only 19.4%, but the courses of these conditions did not seem to significantly affect each other (29, 36). Co-occurrence with anxiety disorders had a bidirectional impact on course: borderline personality disorder exerted negative effects on the course of generalized anxiety disorder (GAD), social phobia, and posttraumatic stress disorder (PTSD), but only PTSD influenced borderline personality disorder, predicting its relapse. Improvement in borderline personality disorder predicted PTSD remission and those with borderline personality disorder had more new onsets of GAD and panic disorder, as well as relapses to obsessive-compulsive disorder (OCD) and panic disorder (27, 28) than other groups. New onsets of substance use disorder occurred more frequently among patients with borderline personality disorder than among those with major depressive disorder and other personality disorders (37).
Longitudinal findings have revised borderline personality disorder’s reputation of treatment resistance with evidence of high rates of remission. However, the findings also have demonstrated less common and more fragile recovery. Prospective longitudinal research also indicates the need for early intervention, with warnings of elevated risk for suicide, costly disability, and risk for persistent psychiatric complexity. Treatment can capitalize on the natural tendency for remission and should focus more on functional improvement to curb the ongoing psychiatric disabilities associated with the disorder.

Controversies: Dimensional Versus Categorical Diagnosis

Dimensional models of diagnosis address limitations of traditional categorical modes (38, 39). For example, the categorical threshold of a minimum of five criteria required for diagnosis is arbitrary. Fewer than five symptoms of borderline personality disorder continue to impair functioning (25). Even a single symptom is associated with significant increases in comorbid psychopathology, suicidal ideation and attempts, psychiatric hospitalizations, and significantly reduced functioning (40). The disorder almost always co-occurs with other diagnoses (41) (Table 2), suggesting it may be best captured by common symptom dimensions, rather than simple stand-alone diagnosis.
TABLE 2. Likelihood of lifetime axis I and II disorders among patients with borderline personality disorder and among a non–borderline personality disorder community sample
Psychiatric disorderOdds ratio (controlled for sociodemographic characteristics)99% CIOdds ratio (unadjusted)99% CI
Any substance use disorder3.2*2.73–3.974.503.57–5.71
Any drug use disorder4.0*3.30–4.725.784.67–7.14
Any anxiety disorder7.7*6.51–9.1914.29*10.87–18.87
Any mood disorder9.1*7.71–10.7814.93*11.63–19.61
 Major depressive disorder2.5*2.07–2.9011.76*9.35–14.93
 Dysthymia3.2*2.51–4.168.33*6.62–10.53
 Bipolar I9.9*8.11–12.0116.39*13.33–20.41
 Bipolar II4.3*3.00–6.033.70*2.71–5.05
Any other personality disorder12.5*10.54–14.8615.87*12.82–19.61
 Paranoid5.8*4.69–7.2512.20*8.93–16.39
 Schizoid4.5*3.55–5.7614.29*8.40–24.39
 Schizotypala26.5*21.53–32.68111.11*66.67–200.00
 Antisocial3.5*2.71–4.406.33*4.76–8.40
 Histrionic6.5*4.90–8.5214.49*6.85–31.25
 Narcissistic14.5*12.12–17.4255.56*40.00–83.33
 Avoidant7.2*5.45–9.5611.63*7.87–17.24
 Dependent8.2*4.65–14.4620.41*9.71–41.67
 Obsessive-compulsive3.73.06–4.527.75*5.65–10.64
a
Authors of report note this figure may be inflated due to the methodologic factors (14).
*p<0.01; adapted from Tomko et al. (14) and Grant et al. (34).
The ICD-11 (42) has shifted to a dimensional classification system. The DSM-5 (43) retains a categorical focus but includes the Alternative Model of Personality Disorders (AMPD), which, like the ICD-11, emphasizes disruptions of self- and interpersonal functioning as central to personality pathology (44). A third dimensional approach to personality diagnosis, the Hierarchical Taxonomy of Psychopathology (HiTOP), proposes a set of empirically derived hierarchical traits that are shared across spectrums of psychiatric conditions (45).
A brief overview of three prominent dimensional models is provided (Table 3). Despite divergence in symptom domains included across these three models, they generally converge with the five-factor model (46). All of these models propose at least five dimensional trait domains by which individual symptoms are more specifically described. The ICD-11 additionally emphasizes level of risk of harm to self or others as a central component of personality disorder severity (47). HiTOP proposes a general psychopathology factor (i.e., the “p” factor) reflecting the individual’s overall predisposition to experience psychiatric problems (48).
TABLE 3. Conceptualization and measurement of overall personality impairment severity and stylistic trait domains across the ICD-11, DSM-5 Alternative Model of Personality Disorders (AMPD), and Hierarchical Taxonomy of Psychopathology (HiTOP) models of dimensional psychopathology
VariableICD-11DSM-5 AMPDHiTOP
Components of global personality disorder severityGlobal severity: self- and interpersonal functioning, risk of harm to self and/or othersCriterion A: self- and interpersonal functioningSuperspectra: general psychopathology severity (p factor)
Specific and/or stylistic trait domainsTrait qualifiers: negative affectivity, detachment, dissociality, disinhibition, anankastiaCriterion B trait domains: negative affectivity, detachment, antagonism, disinhibition, psychoticismSpectra: internalizing, detachment, antagonistic externalizing, disinhibited externalizing, thought disorder, somatoform (provisional)
The ICD-11 has retained a borderline pattern qualifier, defined by the DSM categorical definition, among its classification options, because that conceptualization of the disorder is clinically familiar and compatible with existing interventions and a long body of literature. Simultaneously, the disorder is being dimensionally reconceptualized (49, 50). Substantial symptom overlap across internalizing and externalizing domains (51) suggests the disorder may be more reflective of general psychopathology that is shared across personality disorders (52). Supporting this suggestion, cross-sectional data from two nationally representative samples of U.S. adults (53) have shown high shared variance between the general psychopathology factor and a latent borderline personality disorder factor. Taken together, these findings provide empirical rationale for a reconsideration of borderline personality disorder’s position in diagnostic systems.
However, if the disorder is best captured by a single factor model, an entirely dimensional approach to classification may miss distinct phenotypes that have been identified by previous factor analyses. Although some of these phenotypes are more externalizing or internalizing (e.g., a “highly externalizing, risk taking, reckless” vs. “a mix of affective instability, identity disturbance, and dissociation”) (54), others appear more nuanced (e.g., angry and aggressive vs. angry and mistrustful) or prototypical (55), suggesting that a hybrid dimensional and categorical model is useful. Similarly, 10-year longitudinal data (56) from CLPS have shown that borderline and narcissistic traits in particular are prospectively predictive of suicidal behavior patterns; therefore, dimensional approaches may exclude pertinent categorical phenomena that are relevant to risk assessment.
Clinical translation of dimensional classification remains in its infancy. Preliminary frameworks for integrating the DSM-5 AMPD and HiTOP into practice suggest that assessment of self- and interpersonal impairment (i.e., criterion A severity) may be used to gauge levels of risk and the intensity of treatment that may be required before moving on to assessment of stylistic traits (57, 58). Existing interventions for the disorder already target dimensional trait domains, such as DBT, which addresses negative affectivity and disinhibition with emotion regulation and distress tolerance skills. A published framework (58) for integrating the DSM-5 AMPD into clinical practice acknowledges that targeting criterion B traits would involve clinical approaches that are both common (e.g., attention to therapy alliance) and specific (e.g., cognitive restructuring, psychodynamic interpretation). Therefore, dimensional reformulation of the disorder may not require dramatic alteration of existing treatments. Symptom profiles associated with treatment outcomes should be identified, addressing the unevenness of treatment response that has been observed when conceptualizing the disorder as a categorical entity (13, 59).
Discernment regarding which interventions are best suited to more severe levels of personality disorder is needed. Dimensional models do not conceptualize self-harm and suicidal behavior as distinct phenomena. Rather, these symptoms are subsumed under definitions of broad trait domains (e.g., the DSM-5 AMPD includes self-harm in its description of negative affectivity; HiTOP includes suicidal behavior in the internalizing distress subfactor). Because chronic self-harm and suicidality are often prominent features persisting throughout treatment (60), guidelines for management of self-destructive symptoms are needed.
Studies of dimensional personality classification would benefit from measurement of treatment outcomes in order to address existing gaps in clinical applicability. Examination of self-harm and suicide-related outcomes is crucial. Longitudinal clinical trial designs that assess whether dimensional classification improves prediction of treatment outcomes are needed to determine clinical superiority to existing systems of diagnosis.

Neuroimaging Advances

Over the past decade, the exponential growth of neuroimaging research, with exciting methodological approaches spanning from connectivity analysis to machine learning, has advanced our understanding of the neural basis of borderline personality disorder. Novel findings suggest that this disorder and other psychiatric disorders may share important neurobiological underpinnings—highlighting biomarkers of psychotherapy outcomes and bringing attention to clinical implications regarding interpersonal sensitivity, negative affectivity, and aggression for people with borderline personality disorder.

The Frontolimbic Hypothesis: Shared or Distinct Neurobiological Disruptions?

The most common brain imaging finding across borderline personality disorder research is that the disorder is associated with an imbalance in frontolimbic circuitry, which is thought to underpin emotion dysregulation (61). The emerging shift favoring dimensional psychopathology is concurrent with a proliferation of neuroimaging studies investigating whether frontolimbic disruptions are distinct to borderline pathology or are shared across disorders. Findings from structural and functional imaging studies have provided convincing data indicating that neurobiological abnormalities in borderline personality disorder may not be diagnosis-specific, pointing to a transdiagnostic model of frontolimbic disruptions. Other findings (6275) have suggested a distinct and shared neurobiology between borderline personality disorder and other disorders, supporting a hybrid dimensional-categorical formulation (see Table 4 for review).
TABLE 4. Findings supporting dimensional and hybrid models of diagnosis of borderline personality disordera
Model supportedCitationSampleMethodAnalysis or aimsSummaryImplications
Dimensional neurobiological modelBaranger et al., 2020 (62)N=1,398 scans from the Duke Neurogenetics Study and Human Connectome ProjectStructural MRI152 structural metrics examined (e.g., cortical thickness, cortical surface area, subcortical volumes)Borderline traits not associated with any of 152 structural metrics investigatedTraits that are specific to borderline pathology are not associated with brain structure
 Degasperi et al., 2021 (63)52 studies N=1,104 borderline personality disorder and 1,100 control participantsTask-based fMRI (any task)Activation likelihood estimation meta-analysisNo clusters of significant convergence or differences identified during the performance of any task; when analyses were restricted to emotion processing tasks; two significant clusters of greater activation, in borderline personality disorder vs. controls, in amygdalate and ACCBorderline-specific pathology is not associated broadly with brain function during fMRI task performance
 Traynor et al., 2021 (64)N=45 borderline personality disorder and 29 control participantsResting-state fMRIConnectivity analysisLimbic system connectivity strength in borderline personality disorder significantly associated with severity of impairments in dimensional self- and interpersonal functioning (DSM-5 AMPD criterion A); typology-specific measure of borderline personality disorder symptom severity not significantly associated with any resting-state connectivity patternsLimbic system disruptions are related to dimensional psychopathology impairments and are not borderline personality disorder–specific
 van Zutphen et al., 2017 (65); van Zutphen et al., 2020 (66)N=51 borderline personality disorder, 26 cluster C, and 44 nonpatient control participantsTask-based fMRI (emotion processing task and affective inhibitory control task)Activation analysisInsula and TPJ hyperactivation during emotion processing in borderline personality disorder vs. other groups; hyperactivation in FEF and IPL during inhibition of negative vs. neutral stimuli, in borderline personality disorder vs. other groups; activation differences showed significant linear trend related to diagnostic severity vs. categoryDifferences in brain activation may be related more to the severity of psychopathology vs. diagnostic category
 Kebets et al., 2021 (67)166 females with borderline personality disorder, bipolar disorder, or ADHDResting-state fMRIPartial least squares analysis of resting-state signal variabilityFrontolimbic network signal variability associated with emotion dysregulation across disorders; severity of emotion dysregulation accounted for 74% of shared variance in frontolimbic signal; depression and mania severity not associated with frontolimbic signalEmotion dysregulation-related frontolimbic function is shared across disorders and not specific to borderline personality disorder
 Bilek et al., 2019 (68)N=120 borderline personality disorder vs. 115 control participantsTask-based fMRI (threat processing task)Activation analysisSignificant reduction in amygdala habituation to threat processing in borderline personality disorder vs. controls; effect unrelated to borderline personality disorder symptom severity or category but significantly associated with severity of childhood adversityAbnormalities in brain activation during threat processing may be related more to severity of early adversity vs. categorical borderline personality diagnosis
 Metz et al., 2019 (69)N=18 borderline personality disorder, 20 PTSD, 40 control participantsTask-based fMRIRCT of autobiographical memory (AM) retrieval after administration of 10 mg of hydrocortisone or placeboNo between-group differences in neural activation during AM retrieval after hydrocortisone or placebo; hydrocortisone effects on amPFC, vlPFC, PCC, angular gyrus, and cerebellum positively correlated with childhood trauma questionnaire scoresHydrocortisone-induced neural activation during AM retrieval is related to childhood trauma (vs. borderline personality disorder diagnosis)
 Schaub et al., 2021 (70)N=313 with borderline personality disorder, cocaine use disorder, opioid use disorder, major depressive disorder, schizophrenia, or first-episode psychosisStructural MRIExamined associations between anhedonia and gray matter volumeNegative associations found between volumes of left putamen and bilateral cerebellum with anhedonia scores across disordersClinical problems, such as anhedonia, have shared neurobiological substrates across borderline personality disorder and other disorders
 Neukel et al., 2021 (71)N=45 borderline personality disorder and 25 control participantsTask-based fMRI (emotion processing task)Activation analysisAbnormal precuneus activation during emotion processing of neutral and fearful stimuli in borderline personality disorder related to severity of impairments in self- and interpersonal functioning (DSM-5 AMPD criterion A)Abnormalities in emotion-related brain activation may be related more to severity of psychopathology vs. diagnostic category
 Cremers et al., 2021 (72)N=51 borderline personality disorder, 26 cluster C, and 44 nonpatient control participantsTask-based fMRI (emotion regulation task)Support vector machine classification of borderline personality disorderUnable to classify borderline personality disorder with high accuracy by using brain activation during emotion regulation; 55% classification accuracy was not statistically significant under permutation modelBrain activation during emotion regulation cannot be used to distinguish individuals with borderline personality disorder from those without the disorder
Hybrid dimensional-categorical neurobiological modelYu et al., 2019 (73)13 borderline personality disorder studies (N=395 borderline personality disorder and 415 control participants) and 47 bipolar disorder studies (N=2,111 bipolar disorder and 3,261 control participants)Structural MRIMeta-analysis of gray matter volume and density in borderline personality disorder vs. bipolar disorderShared: decreased gray matter volume and density in right medial OFC; specific to borderline personality disorder: decreased gray matter volume and density in amygdala and right parahippocampal gyrus; specific to bipolar disorder: decreased gray matter volume and density in right insula and thalamus and increased volume and density in right putamen (and putamen volume correlated with young mania rating scale scores)Borderline personality disorder and bipolar disorder have both shared and distinct neural substrates
 Lou et al., 2021 (74)15 borderline personality disorder datasets (N=442 borderline personality disorder and 441 control participants) and 11 PTSD datasets (N=214 PTSD and 258 control participants)Structural MRIMeta-analysis of gray matter volume in borderline personality disorder vs. PTSDShared: gray matter volume reductions in orbitofrontal gyrus and anterior cingulate cortex; specific to borderline personality disorder: gray matter volume increases in PCC/precuneus; specific to PTSD: gray matter volume decreases in amygdala and hippocampusBorderline personality disorder and PTSD have both shared and distinct neural substrates
 De la Peña-Arteaga et al., 2021 (75)N=19 borderline personality disorder, 20 major depressive disorder, and 19 control participantsTask-based fMRI (cognitive reappraisal task)Activation analysisShared: decreased vlPFC activation during cognitive reappraisal; specific to major depressive disorder: overall prefrontal hypoactivation; specific to borderline personality disorder: abnormalities attributed to connectivity disruptions between vlPFC and temporal regionsBorderline personality disorder and major depressive disorder both have shared and distinct neural substrates
a
ACC, anterior cingulate cortex; amPFC, anterior medial prefrontal cortex; FEF, frontal eye fields; FFI-BPD, Five-Factor Inventory borderline personality disorder composite; fMRI, functional magnetic resonance imaging; IPL, inferior parietal lobe; NEO-FFI, NEO Five-Factor Inventory; OFC, orbitofrontal cortex; PCC, posterior cingulate cortex; RCT, randomized control trial; TPJ, temporal parietal junction; vlPFC, ventrolateral prefrontal cortex.
Structural and functional imaging studies powered to detect effects (∼N>1,000) provide strong evidence that neurobiological abnormalities in borderline personality disorder are not disorder specific. The largest structural MRI study (62) to date found no associations between borderline personality disorder traits and any of the 152 structural metrics examined. Similarly, a large meta-analysis of task-based functional MRI (fMRI) studies, which used activation likelihood estimation to compare participants with borderline personality disorder versus healthy control participants (63), found no clusters of significant convergence or difference. Instead, neurobiological alterations in borderline personality disorder appeared to be associated more with severity rather than with diagnostic category, as well as with phenomena that cut across disorders, such as emotion dysregulation, severity of childhood adversity, and anhedonia (6472). On the other hand, some findings (7375) have pointed to both shared and distinct neurobiological alterations in borderline personality disorder versus major depressive disorder, bipolar disorder, and PTSD.

Interpersonal Hypersensitivity, Negative Affectivity, and the Default Mode Network (DMN)

Disruptions in the functioning of the DMN may play a role in the interpersonal and affective features of borderline personality disorder. The DMN is composed of a set of brain structures along the cortical midline and in temporal, parietal, and subcortical areas. The DMN is most active during introspection or rumination (i.e., self-referential processing) as well as during mentalizing (i.e., social cognition) (7678). During more “task on” executive performance (e.g., working memory or inhibition tasks), the DMN deactivates or “ramps down” to support the activation and coordination of other networks involved in executive functioning (e.g., central executive and attentional networks). Findings from a study of working memory (79) suggest that relative to control participants, the DMN in participants with borderline personality disorder did not show typical deactivation during executive task performance. Participants with borderline personality disorder also showed less activation in more typical executive areas of the brain during working memory performance (79). These findings suggest that individuals with the disorder may have difficulty “turning off the DMN” (i.e., disengaging from social cognition) while completing executive tasks (79) (e.g., focusing on how others are perceiving them at the expense of task efficiency). In turn, such difficulties may underpin hypermentalization, which is defined as making complex inferences of what another person is thinking without ostensible evidence (80, 81). A recent systematic review (82) reported findings that the DMN is often overactive in people with borderline personality disorder, and this overactivation is related to impaired social cognition. In another study (83), relative to healthy control participants and individuals with low self-esteem, the DMN of participants with borderline personality disorder was overactivated in response to insults, compared with compliments. Similar results have been observed during the Cyberball task, which simulates conditions of social inclusion and exclusion. Compared with healthy control participants, self-harming participants without borderline personality disorder, and individuals with major depressive disorder, participants with borderline personality disorder show overactivation in regions of the DMN during both social inclusion and exclusion, reflecting heightened relational sensitivity (8486). One of these studies (84) found that high negative affect among participants with borderline personality disorder moderated the extent of DMN reactivity to social exclusion, suggesting that interpersonal reactivity among people with borderline personality disorder may oscillate with transient emotion states. Social exclusion also appears to impair effortful control and mentalization abilities of individuals with high, but not low, borderline personality disorder traits (87). Taken together, these findings underscore the magnitude of interpersonal hypersensitivity among those with borderline personality disorder and the strong influence that social exclusion can have on executive and social functioning.
Two other studies have further underscored the impact of negative affectivity on hypersensitivity among people with borderline personality disorder. One study (88) found increased neurobiological reactivity to repeated presentations of both negative and neutral emotional stimuli among those with borderline personality disorder, relative to those with avoidant personality disorder and to a healthy comparison group, and neurobiological reactivity was again moderated by ratings of negative affect among the group with borderline personality disorder. The other study (89) found a relationship between the magnitude of brain activation during a negative affective-inhibitory control task and the lethality of past suicidal behavior of individuals with borderline personality disorder, suggesting that negative affective states may also have an impact on cognitive processing and the medical seriousness of suicide attempts.
These findings highlight the relevance of strategies to enhance self-management to reduce negative affect and associated cognitive impairment and disinhibition (e.g., self-harm or suicidal behavior), which are likely to follow interpersonal conflict (e.g., rejection) among people with the disorder (90). The disorder appears associated with reactivity to both acceptance and rejection and to negative and neutral emotional stimuli, thereby underscoring the importance of interventions that target emotional and interpersonal hypersensitivity.

Biomarkers of Aggression and Hostility in Borderline Personality Disorder

Sex-specific aggression biomarkers in borderline personality disorder represent another emerging research direction. In a study with a sex-balanced sample (91), a script-driven aggression imagery fMRI study found that anger in males with the disorder (relative to females with the disorder and to control males) may be related to abnormal coupling of the prefrontal cortex with the amygdala. This finding converges with that of another study (92) which found a sex-specific association between externalizing anger and prefrontal-amygdala function in males with the disorder. Another analysis of females with the disorder (93) showed increased anger-related brain connectivity across a more extensive functional brain network, suggesting more comprehensive neural coordination during anger processing among females with the disorder.
Poor top-down control of aggression among males with borderline personality disorder has been inferred and the importance of sex-specific, anger regulation treatment targets emphasized (91). Interestingly, findings from a pilot treatment study of aggression-specific psychotherapy versus treatment as usual (71) found significant effects of aggression-specific treatment, but not of treatment as usual, on amygdala-prefrontal coupling, suggesting that interventions specifically targeting aggression may indeed help to correct or normalize anger-related frontolimbic disturbances among those with borderline personality disorder. A recent finding also suggests that fatty acid amide hydrolase (FAAH) inhibitors may be explored as a future pharmacotherapeutic option for aggression in borderline personality disorder; in the first positron emission tomography study of its kind (94), FAAH in the prefrontal cortex and amygdala of participants with borderline personality disorder was positively associated with measures of hostility.

Self-Harm in Borderline Personality Disorder and Biomarkers of Psychotherapy Outcomes

Progress in identifying biomarkers of self-harm and psychotherapy outcomes has developed in the last decade. A recent systematic review (95) on the neural substrates of self-harm in the disorder shows that self-harm is related to disruptions in impulse-control and affective brain regions. In one study (96), compared with control participants and participants with the disorder without self-harming behavior, patients with the disorder and self-harming behavior exhibited greater amygdala activation during repeated presentations of aversive stimuli, reflecting increased neurobiological sensitivity. Other studies have shown that the application of painful stimuli after social exclusion versus inclusion is associated with hyperactivation of the nucleus accumbens, a reward-related region, among participants with the disorder. This effect was mediated by anxious attachment style, implicating a reward-related function to self-harm following social rejection among anxiously attached individuals with borderline personality disorder (97). Along the same lines, another study (96) observed a dampening of amygdala activation in response to painful stimuli, providing further evidence for a regulating function of self-harm among people with the disorder. In Niedtfeld et al.’s study (98), DBT, but not treatment as usual, restored amygdala reactivity during pain processing among people with borderline personality disorder to that seen among healthy control participants.
Psychotherapy improvements among people with the disorder appear to be mediated by changes in prefrontal-limbic circuitry, with treatment-related effects commonly yoked to the structure and function of the amygdala and the anterior cingulate cortex (ACC) (99, 100). Neurobiological changes after treatment for borderline personality disorder are thought to reflect increased executive control and improved emotion regulation (100). After DBT and psychodynamic therapy, less amygdala activation is observed, with more heterogeneity in the directionality of prefrontal effects (99, 101, 102). In particular, the dorsal ACC is a candidate biomarker of psychotherapy change, which may be related to its role in appraisal and error-monitoring (99). Multimodal imaging findings (103) have shown an association between ACC connectivity and the use of negative cognitive emotion regulation strategies among unmedicated individuals with borderline personality disorder, relative to control participants. Changes in dorsal ACC connectivity during cognitive reappraisal following psychotherapy have also been shown (104).

Treatment

Numerous assessments are now validated for screening and diagnosing and for measuring changes in borderline personality disorder symptoms (33). However, clinical diagnosis can be made easily by reviewing the DSM-5 section II or III criteria collaboratively with patients to evaluate which features relate to their history of care. Stigma perpetuates reluctance to deliver “bad news” to patients despite the positive prognosis and relevant treatment options. Studies have reported that the diagnostic disclosure of borderline personality disorder is tolerated similarly to other diagnoses among adults (104) and was not a negative experience for adolescents but rather one that accurately captured their problems (105). Screening all patients by using the criterion of affective instability has been shown sensitive to detecting cases of borderline personality disorder for further evaluation (106).

Psychotherapy

Several psychotherapies effectively treat borderline personality disorder (1, 2, 107). Focus’s prior review described four empirically supported approaches—DBT, MBT, transference-focused psychotherapy, and good psychiatric management, which all have some empirical support and dissemination systems. Schema-focused therapy has also proven effective for the disorder, with a recent report (108) showing that a combination of group and individual schema-focused therapy led to greater reductions in borderline personality disorder severity than group schema-focused therapy alone or treatment as usual. Although these treatment approaches differ in their underlying theories of the development of the disorder and mechanism of change, they share common characteristics requiring structured roles and goals that organize the working relationship between clinician and patient. Across meta-analyses, no one therapy approach has been shown to be superior to others nor has duration or intensity determined outcome (59). Psychotherapies for borderline personality disorder remain among the few validated interventions for self-harm, among both adolescents and adults (109, 110). These therapies also improve anger, impulsivity, depression, and interpersonal problems (107). DBT and MBT stand out as the approaches with the best evidence (107). Treatments that are specifically tailored for the disorder work better compared with treatments that are not, whether they are specialist treatments requiring intensive training or generalist approaches, such as good psychiatric management and structured clinical management (2, 111114).
In recognition that the treatment supply remains severely inadequate to meet demand (11), research has focused on less intensive, briefer treatments, which are proving effective and adequate for patients at acute and outpatient levels of care (115117). Studies comparing 6-month to usual 12-month variants of DBT and MBT are nearing completion, showing promising results that justify shortening the length of treatment to expand supply (118). A recent report from McMain and colleagues’ (119) Feasibility of a Shorter Treatment and Evaluating Responses (FASTER) randomized controlled trial with 240 participants showed that 6 months of DBT was not inferior to 12 months, even at 24-month follow-up. Adjunctive treatments have also received substantial empirical support. Trials of systems training for emotional predictability and problem solving, DBT-skills training, and a brief psychoeducational bibliotherapy called manual-assisted cognitive therapy, demonstrate the utility of augmenting ongoing “good-enough” clinical care with these add-on modalities (120). Briefer treatments, ranging in length from 1 to 6 months, prior to potential transition to longer-term outpatient care, also show promise in reaching symptomatic stability and limiting suicidality and self-harm (115119, 121). Stepped-care models that aim to optimally allocate resources according to clinical staging have been developed but need testing (122, 123).
Complex comorbidity is the rule rather than exception for people with borderline personality disorder (Table 2). Nearly half of those with borderline personality disorder also meet criteria for substance or alcohol use disorder (36), and one-third have co-occurring PTSD (28, 30). Progress in combining treatment for common co-occurring disorders has been made. Dynamic deconstructive psychotherapy, a psychodynamic-oriented approach designed to promote emotional processing to reduce black and white thinking, has two trials supporting its use (124, 125). DBT-PTSD, found to be effective in reducing PTSD and borderline personality disorder symptoms among patients with severe chronic childhood abuse, integrates DBT, acceptance and commitment therapy, and exposure, specifically targeting traumatic memory processing, self-concept, and social interactions (126). These treatments enable clinicians to deliver more parsimonious care.
Treatments for the disorder routinely encourage involvement of family members (i.e., caregivers) and significant others, which reduces relapse, facilitates treatment, and improves quality of family life (127). Several family support programs have been developed on the basis of DBT, MBT, and psychoeducation (127). All combine psychoeducation with skills training tailored for caregivers and family members, which enhances support for the patient to foster and sustain changes. Examples of guidelines for families are widely available at no cost (e.g., www.borderlinepersonalitydisorder.org/family-guidelines).

Pharmacology and Novel Brain-Based Therapeutics

Limited research on medication management for borderline personality disorder has been published in the last decade (127130), and no medication has been approved by the Food and Drug Administration for the treatment of the disorder. Paradoxically, over 90% of patients with the disorder receive at least one psychotropic medication. Polypharmacy is common, with almost one in five patients receiving more than four psychotropic agents simultaneously (130). Treatment guidelines (131133) diverge, with some advising against the use of medications and others prescribing symptom-based algorithms. Meta-analytic studies have indicated that mood stabilizers diminish symptoms of affective lability (especially anger), and second-generation antipsychotics improve general psychiatric severity of patients with borderline personality disorder (128). However, the quality of evidence for pharmacology studies for the disorder remains low and inconsistent. Placebo response is significant. In one of the largest trials to date, lamotrigine and placebo yielded significant treatment responses in 4 months, but without significant differences between them, suggesting the risks and costs inherent in lamotrigine were not justified (134). These outcomes suggest high quality psychiatric management focused on the disorder may exert an important treatment effect apart from specific psychotropic mechanisms (135). According to expert consensus, the main role of medications is to treat the usual co-occurring disorders that patients with borderline personality disorder have (128, 129). Recent studies (129) also have shown that combining medications with psychotherapy yields greater improvement in borderline personality disorder symptoms than either treatment alone.
Guidelines recommend conservative prescribing with attention to collaborative monitoring of targeted symptoms, discontinuing when not producing clear benefits, and short-term usage to minimize side effects. For most co-occurring diagnoses, the treatment of borderline personality disorder as a priority will improve symptoms of the other disorders (111). In the case of ADHD, anorexia, and substance use disorder, the priority is to treat these entities to promote learning. With OCD, panic disorder, and PTSD, stabilization of borderline personality disorder symptoms may make exposure treatments more tenable (136).
Noninvasive brain stimulation interventions are effective for reducing depression and suicidal ideation among people with treatment-resistant major depressive disorder (137), inspiring studies of their effectiveness with these symptoms for patients with borderline personality disorder. Although most findings have been preliminary, from small samples and unblinded trials, they have shown initial promise and warrant more rigorous testing. Evidence from a systematic review (138) of 24 studies on brain stimulation (most with repetitive transcranial magnetic stimulation [rTMS] of the dorsolateral or dorsomedial prefrontal cortex) among patients with borderline personality disorder supports the safety, tolerability, and preliminary efficacy of rTMS for borderline personality disorder, with the majority of these investigations reporting reductions in symptom domains of impulsivity, anger, emotion dysregulation, anxiety, and depression severity. However, only two rTMS trials to date (139, 140) have used a sham-controlled design involving rTMS over the dorsomedial prefrontal cortex, with findings favoring active rTMS for improving depression, anxiety, and impulsiveness. Prior reports also have shown reduced effectiveness of electroconvulsive therapy (ECT) for depression among patients with borderline personality disorder. However, two recent studies (141, 142) found that ECT was effective for treating depression of patients who screened positive on the McLean Screening Instrument for borderline personality disorder, although those findings may be limited in their generalizability to individuals meeting formal diagnostic criteria (143).

Conclusions

Over the last decade of progress, our field’s understanding of borderline personality disorder’s specific characteristics as a prevalent, sometimes fatal, disabling, but treatable condition, has solidified as dimensional conceptualizations of psychopathology have moved psychiatry into new directions. Research demonstrating borderline personality disorder’s unique and shared neuroscientific characteristics has provided a basis for understanding both common and distinct features of the disorder. These advances support a move toward a hybrid or integrative model of understanding borderline personality disorder that appears to represent fundamental features of general personality dysfunction more broadly. The treatments proven for the disorder may in fact be transdiagnostically effective across personality disorders as well as the major comorbid conditions of borderline personality disorder. Research elucidates that the disorder’s biological basis relates to both emotional and interpersonal hypersensitivity, showing that negative affectivity interrupts usual regulation of cognitive processes that support switches between DMN-driven reflection and executive and attentional functions that support effective decision making and action. Furthermore, there are sex-specific differences regarding aggression, but few treatments have been tested on adequately balanced samples of males and females, pointing to the need for more representative treatment samples in future studies.
Treatment research is actively refining what we already know. Psychotherapeutic interventions are primary, whereas pharmacologic and other brain-based therapeutics are adjunctive, specifically to treat co-occurring disorders. In the last decade, evidence that expands our clinical armamentarium to generalist, acute, and briefer steps of care confronts the reality that treatment is rarely one-size-fits-all for any disorder. Future studies should focus on answering which, if any, pharmacologic or brain-based therapeutics enhance psychotherapies or clinical management enough to clarify new basic standards of care. Earlier intervention and focus on functional rehabilitation over symptomatic remission are new directions that hold the potential to curb the detriments of the disorder over the course of a patient’s lifetime to enable more stable engagement in the usual life-building activities, such as work and love, that define human personality functioning. With the life-altering impact of COVID-19, the need for digital and telehealth interventions, which are showing preliminary promise, will become more central (144, 145). Continuing research and treatment for borderline personality disorder is crucial and hopeful, as reflected in life-changing discoveries and developments.

REFERENCES

1.
Gunderson JG, Weinberg I, Choi-Kain L: Borderline personality disorder. Focus 2013; 11:129–145
2.
Choi-Kain LW, Finch EF, Masland SR, et al: What works in the treatment of borderline personality disorder. Curr Behav Neurosci Rep 2017; 4:21–30
3.
Yen S, Peters JR, Nishar S, et al: Association of borderline personality disorder criteria with suicide attempts: findings from the collaborative longitudinal study of personality disorders over 10 years of follow-up. JAMA Psychiatry 2021; 78:187–194
4.
Tate AE, Sahlin H, Liu S, et al: Borderline personality disorder: associations with psychiatric disorders, somatic illnesses, trauma, and adverse behaviors. Mol Psychiatry 2022; 27:2514–2521
5.
Temes CM, Zanarini MC: The longitudinal course of borderline personality disorder. Psychiatr Clin North Am 2018; 41:685–694
6.
Ansell EB, Sanislow CA, McGlashan TH, et al: Psychosocial impairment and treatment utilization by patients with borderline personality disorder, other personality disorders, mood and anxiety disorders, and a healthy comparison group. Compr Psychiatry 2007; 48:329–336
7.
Pascual JC, Córcoles D, Castaño J, et al: Hospitalization and pharmacotherapy for borderline personality disorder in a psychiatric emergency service. Psychiatr Serv 2007; 58:1199–1204
8.
Hong V: Borderline personality disorder in the emergency department: good psychiatric management. Harv Rev Psychiatry 2016; 24:357–366
9.
Zimmerman M, Chelminski I, Young D, et al: The frequency of personality disorders in psychiatric patients. Psychiatr Clin North Am 2008; 31:405–420
10.
Soeteman DI, Hakkaart-van Roijen L, Verheul R, et al: The economic burden of personality disorders in mental health care. J Clin Psychiatry 2008; 69:259–265
11.
Iliakis EA, Sonley AKI, Ilagan GS, et al: Treatment of borderline personality disorder: is supply adequate to meet public health needs? Psychiatr Serv 2019; 70:772–781
12.
Iliakis EA, Ilagan GS, Choi-Kain LW, et al: Dropout rates from psychotherapy trials for borderline personality disorder: a meta-analysis. Personal Disord 2021; 12:193–206
13.
Woodbridge J, Townsend M, Reis S, et al: Non-response to psychotherapy for borderline personality disorder: a systematic review. Aust N Z J Psychiatry 2022; 56:771–787
14.
Tomko RL, Trull TJ, Wood PK, et al: Characteristics of borderline personality disorder in a community sample: comorbidity, treatment utilization, and general functioning. J Pers Disord 2014; 28:734–750
15.
Kaess M, Brunner R, Chanen A, et al: Borderline personality disorder in adolescence. Pediatrics 2014; 134:782–793
16.
Soloff PH, Lynch KG, Kelly TM, et al: Characteristics of suicide attempts of patients with major depressive episode and borderline personality disorder: a comparative study. Am J Psychiatry 2000; 157:601–608
17.
Stepp SD, Scott LN, Jones NP, et al: Negative emotional reactivity as a marker of vulnerability in the development of borderline personality disorder symptoms. Dev Psychopathol 2016; 28:213–224
18.
Winsper C, Hall J, Strauss VY, et al: Aetiological pathways to borderline personality disorder symptoms in early adolescence: childhood dysregulated behaviour, maladaptive parenting and bully victimisation. Borderline Personal Disord Emot Dysregul 2017; 4:10
19.
Cohen P, Crawford TN, Johnson JG, et al: The children in the community study of developmental course of personality disorder. J Pers Disord 2005; 19:466–486
20.
Stepp SD, Scott LN, Morse JQ, et al: Emotion dysregulation as a maintenance factor of borderline personality disorder features. Compr Psychiatry 2014; 55:657–666
21.
Winsper C, Wolke D, Scott J, et al: Psychopathological outcomes of adolescent borderline personality disorder symptoms. Aust N Z J Psychiatry 2020; 54:308–317
22.
Winograd G, Cohen P, Chen H, et al: Adolescent borderline symptoms in the community: prognosis for functioning over 20 years. J Child Psychol Psychiatry 2008; 49:933–941
23.
Choi-Kain LW, Sharp C (eds): Handbook of Good Psychiatric Management for Adolescents with Borderline Personality Disorder. Washington, DC, American Psychiatric Association, 2021
24.
Gunderson JG, Stout RL, McGlashan TH, et al: Ten-year course of borderline personality disorder: psychopathology and function from the Collaborative Longitudinal Personality Disorders Study. Arch Gen Psychiatry 2011; 68:827–837
25.
Zanarini MC, Frankenburg FR, Reich DB, et al: Attainment and stability of sustained symptomatic remission and recovery among patients with borderline personality disorder and axis II comparison subjects: a 16-year prospective follow-up study. Am J Psychiatry 2012; 169:476–483
26.
Gunderson JG, Daversa MT, Grilo CM, et al: Predictors of 2-year outcome for patients with borderline personality disorder. Am J Psychiatry 2006; 163:822–826
27.
Shea MT, Stout RL, Yen S, et al: Associations in the course of personality disorders and axis I disorders over time. J Abnorm Psychol 2004; 113:499–508
28.
Ansell EB, Pinto A, Edelen MO, et al: The association of personality disorders with the prospective 7-year course of anxiety disorders. Psychol Med 2011; 41:1019–1028
29.
Gunderson JG, Stout RL, Shea MT, et al: Interactions of borderline personality disorder and mood disorders over 10 years. J Clin Psychiatry 2014; 75:829–834
30.
Keuroghlian AS, Gunderson JG, Pagano ME, et al: Interactions of borderline personality disorder and anxiety disorders over 10 years. J Clin Psychiatry 2015; 76:1529–1534
31.
Skodol AE, Gunderson JG, McGlashan TH, et al: Functional impairment in patients with schizotypal, borderline, avoidant, or obsessive-compulsive personality disorder. Am J Psychiatry 2002; 159:276–283
32.
Gunderson JG, Herpertz SC, Skodol AE, et al: Borderline personality disorder. Nat Rev Dis Primers 2018; 4:18029
33.
Hastrup LH, Jennum P, Ibsen R, et al: Welfare consequences of early-onset borderline personality disorder: a nationwide register-based case-control study. Eur Child Adolesc Psychiatry 2022; 31:253–260
34.
Grant BF, Chou SP, Goldstein RB, et al: Prevalence, correlates, disability, and comorbidity of DSM-IV borderline personality disorder: results from the Wave 2 National Epidemiologic Survey on Alcohol and Related Conditions. J Clin Psychiatry 2008; 69:533–545
35.
Grilo CM, Stout RL, Markowitz JC, et al: Personality disorders predict relapse after remission from an episode of major depressive disorder: a 6-year prospective study. J Clin Psychiatry 2010; 71:1629–1635
36.
Gunderson JG, Weinberg I, Daversa MT, et al: Descriptive and longitudinal observations on the relationship of borderline personality disorder and bipolar disorder. Am J Psychiatry 2006; 163:1173–1178
37.
Walter M, Gunderson JG, Zanarini MC, et al: New onsets of substance use disorders in borderline personality disorder over 7 years of follow‐ups: findings from the Collaborative Longitudinal Personality Disorders Study. Addiction 2009; 104:97–103
38.
Markon KE, Chmielewski M, Miller CJ, et al: The reliability and validity of discrete and continuous measures of psychopathology: a quantitative review. Psychol Bull 2011; 137:856–879
39.
Regier DA, Narrow WE, Clarke DE, et al: DSM-5 field trials in the United States and Canada, part II: test-retest reliability of selected categorical diagnoses. Am J Psychiatry 2013; 170:59–70
40.
Zimmerman M, Chelminski I, Young D, et al: Does the presence of one feature of borderline personality disorder have clinical significance? Implications for dimensional ratings of personality disorders. J Clin Psychiatry 2012; 73:8–12
41.
Shah R, Zanarini MC: Comorbidity of borderline personality disorder: current status and future directions. Psychiatr Clin North Am 2018; 41:583–593
42.
International Classification of Diseases for Mortality and Morbidity Statistics, 11th ed. Geneva, World Health Organization, 2018
43.
Diagnostic and Statistical Manual of Mental Disorders, 5th ed. Arlington, VA, American Psychiatric Association, 2013
44.
Skodol AE, Clark LA, Bender DS, et al: Proposed changes in personality and personality disorder assessment and diagnosis for DSM-5 part I: description and rationale. Personal Disord 2011; 2:4–22
45.
Kotov R, Krueger RF, Watson D, et al: The Hierarchical Taxonomy of Psychopathology (HiTOP): a quantitative nosology based on consensus of evidence. Annu Rev Clin Psychol 2021; 17:83–108
46.
Widiger TA, Costa PT Jr: Integrating normal and abnormal personality structure: the five-factor model. J Pers 2012; 80:1471–1506
47.
ICD-11 Classification of Mental and Behavioural Disorders. Geneva, World Health Organization. https://icd.who.int/en. Accessed Aug 8, 2022
48.
Caspi A, Houts RM, Belsky DW, et al: The p factor: one general psychopathology factor in the structure of psychiatric disorders? Clin Psychol Sci 2014; 2:119–137
49.
Meisner MW, Bach B, Lenzenweger MF, et al: Reconceptualization of borderline conditions through the lens of the alternative model of personality disorders. Personal Disord 2022; 13:266–276
50.
Sharp C, Kerr S, Barkauskienė R: The incremental utility of maladaptive self and identity functioning over general functioning for borderline personality disorder features in adolescents. Personal Disord (Epub Feb 24, 2022). doi: 10.1037/per0000547
51.
Bailey AJ, Finn PR: Borderline personality disorder symptom comorbidity within a high externalizing sample: relationship to the internalizing-externalizing dimensional structure of psychopathology. J Pers Disord 2020; 34:814–826
52.
Sharp C, Wright AGC, Fowler JC, et al: The structure of personality pathology: both general (‘g’) and specific (‘s’) factors? J Abnorm Psychol 2015; 124:387–398
53.
Gluschkoff K, Jokela M, Rosenström T, et al: General psychopathology factor and borderline personality disorder: evidence for substantial overlap from two nationally representative surveys of US adults. Personal Disord 2021; 12:86–92
54.
Johnson BN, Levy KN: Identifying unstable and empty phenotypes of borderline personality through factor mixture modeling in a large nonclinical sample. Personal Disord 2020; 11:141–150
55.
Hallquist MN, Pilkonis PA: Refining the phenotype of borderline personality disorder: diagnostic criteria and beyond. Personal Disord 2012; 3:228–246
56.
Ansell EB, Wright AGC, Markowitz JC, et al: Personality disorder risk factors for suicide attempts over 10 years of follow-up. Personal Disord 2015; 6:161–167
57.
Ruggero CJ, Kotov R, Hopwood CJ, et al: Integrating the Hierarchical Taxonomy of Psychopathology (HiTOP) into clinical practice. J Consult Clin Psychol 2019; 87:1069–1084
58.
Hopwood CJ: A framework for treating DSM-5 alternative model for personality disorder features. Personal Ment Health 2018; 12:107–125
59.
Cristea IA, Gentili C, Cotet CD, et al: Efficacy of psychotherapies for borderline personality disorder: a systematic review and meta-analysis. JAMA Psychiatry 2017; 74:319–328
60.
DeCou CR, Comtois KA, Landes SJ, et al: Dialectical behavior therapy is effective for the treatment of suicidal behavior: a meta-analysis. Behav Ther 2019; 50:60–72
61.
Sicorello M, Schmahl C: Emotion dysregulation in borderline personality disorder: a fronto-limbic imbalance? Curr Opin Psychol 2021; 37:114–120
62.
Baranger DAA, Few LR, Sheinbein DH, et al: Borderline personality traits are not correlated with brain structure in two large samples. Biol Psychiatry Cogn Neurosci Neuroimaging 2020; 5:669–677
63.
Degasperi G, Cristea IA, Di Rosa E, et al: Parsing variability in borderline personality disorder: a meta-analysis of neuroimaging studies. Transl Psychiatry 2021; 11:314
64.
Traynor JM, Wrege JS, Walter M, et al: Dimensional personality impairment is associated with disruptions in intrinsic intralimbic functional connectivity. Psychol Med 2021; 11:1–11
65.
van Zutphen L, Siep N, Jacob GA, et al: Always on guard: emotion regulation in women with borderline personality disorder compared to nonpatient controls and patients with cluster-C personality disorder. J Psychiatry Neurosci 2017; 43:170008
66.
van Zutphen L, Siep N, Jacob GA, et al: Impulse control under emotion processing: an fMRI investigation in borderline personality disorder compared to non-patients and cluster-C personality disorder patients. Brain Imaging Behav 2020; 14:2107–2121
67.
Kebets V, Favre P, Houenou J, et al: Fronto-limbic neural variability as a transdiagnostic correlate of emotion dysregulation. Transl Psychiatry 2021; 11:545
68.
Bilek E, Itz ML, Stößel G, et al: Deficient amygdala habituation to threatening stimuli in borderline personality disorder relates to adverse childhood experiences. Biol Psychiatry 2019; 86:930–938
69.
Metz S, Fleischer J, Gärnter M, et al: Effects of hydrocortisone on autobiographical memory retrieval in patients with posttraumatic stress disorder and borderline personality disorder: the role of childhood trauma. Neuropsychopharmacology 2019; 44:2038–2044
70.
Schaub AC, Kirschner M, Schweinfurth N, et al: Neural mapping of anhedonia across psychiatric diagnoses: a transdiagnostic neuroimaging analysis. Neuroimage Clin 2021; 32:102825
71.
Neukel C, Bertsch K, Wenigmann M, et al: A mechanism-based approach to anti-aggression psychotherapy in borderline personality disorder: group treatment affects amygdala activation and connectivity. Brain Sci 2021; 11:1627
72.
Cremers H, van Zutphen L, Duken S, et al: Borderline personality disorder classification based on brain network measures during emotion regulation. Eur Arch Psychiatry Clin Neurosci 2021; 271:1169–1178
73.
Yu H, Meng YJ, Li XJ, et al: Common and distinct patterns of grey matter alterations in borderline personality disorder and bipolar disorder: voxel-based meta-analysis. Br J Psychiatry 2019; 215:395–403
74.
Lou J, Sun Y, Cui Z, et al: Common and distinct patterns of gray matter alterations in borderline personality disorder and posttraumatic stress disorder: a dual meta-analysis. Neurosci Lett 2021; 741:135376
75.
De la Peña-Arteaga V, Berruga-Sánchez M, Steward T, et al: An fMRI study of cognitive reappraisal in major depressive disorder and borderline personality disorder. Eur Psychiatry 2021; 64:e56
76.
Uddin LQ: Salience processing and insular cortical function and dysfunction. Nat Rev Neurosci 2015; 16:55–61
77.
Buckner RL, Andrews-Hanna JR, Schacter DL, et al: The brain’s default network: anatomy, function, and relevance to disease. Ann N Y Acad Sci 2008; 1124:1–38
78.
Whitfield-Gabrieli S, Ford JM: Default mode network activity and connectivity in psychopathology. Annu Rev Clin Psychol 2012; 8:49–76
79.
Aguilar-Ortiz S, Salgado-Pineda P, Vega D, et al: Evidence for default mode network dysfunction in borderline personality disorder. Psychol Med 2020; 50:1746–1754
80.
Sharp C, Vanwoerden S: Hypermentalizing in borderline personality disorder: a model and data. J Infant Child Adolesc Psychother 2015; 14:33–45
81.
Somma A, Ferrara M, Terrinoni A, et al: Hypermentalizing as a marker of borderline personality disorder in Italian adolescents: a cross-cultural replication of Sharp and colleagues’ (2011) findings. Borderline Personal Disord Emot Dysregul 2019; 6:5
82.
Rappaport BI, Barch DM: Brain responses to social feedback in internalizing disorders: a comprehensive review. Neurosci Biobehav Rev 2020; 118:784–808
83.
van Schie CC, Chiu CD, Rombouts SARB, et al: Stuck in a negative me: fMRI study on the role of disturbed self-views in social feedback processing in borderline personality disorder. Psychol Med 2020; 50:625–635
84.
Wrege JS, Ruocco AC, Euler S, et al: Negative affect moderates the effect of social rejection on frontal and anterior cingulate cortex activation in borderline personality disorder. Cogn Affect Behav Neurosci 2019; 19:1273–1285
85.
Malejko K, Neff D, Brown RC, et al: Neural signatures of social inclusion in borderline personality disorder versus non-suicidal self-injury. Brain Topogr 2019; 32:753–761
86.
Malejko K, Neff D, Brown RC, et al: Neural correlates of social inclusion in borderline personality disorder. Front Psychiatry 2018; 9:653
87.
Sato M, Fonagy P, Luyten P, et al: Effects of social exclusion on effortful control and mentalizing in relation to borderline personality features. Sci Rep 2018; 8:14400
88.
Denny BT, Fan J, Fels S, et al: Sensitization of the neural salience network to repeated emotional stimuli following initial habituation in patients with borderline personality disorder. Am J Psychiatry 2018; 175:657–664
89.
Soloff PH, Chowdury A, Diwadkar VA, et al: Affective interference in borderline personality disorder: the lethality of suicidal behavior predicts functional brain profiles. J Affect Disord 2019; 252:253–262
90.
Brodsky BS, Groves SA, Oquendo MA, et al: Interpersonal precipitants and suicide attempts in borderline personality disorder. Suicide Life Threat Behav 2006; 36:313–322
91.
Herpertz SC, Nagy K, Ueltzhöffer K, et al: Brain mechanisms underlying reactive aggression in borderline personality disorder—sex matters. Biol Psychiatry 2017; 82:257–266
92.
Bertsch K, Krauch M, Roelofs K, et al: Out of control? Acting out anger is associated with deficient prefrontal emotional action control in male patients with borderline personality disorder. Neuropharmacology 2019; 156:107463
93.
Ueltzhöffer K, Herpertz SC, Krauch M, et al: Whole-brain functional connectivity during script-driven aggression in borderline personality disorder. Prog Neuropsychopharmacol Biol Psychiatry 2019; 93:46–54
94.
Kolla NJ, Mizrahi R, Karas K, et al: Elevated fatty acid amide hydrolase in the prefrontal cortex of borderline personality disorder: a [11C]CURB positron emission tomography study. Neuropsychopharmacology 2020; 45:1834–1841
95.
Dusi N, Bracco L, Bressi C, et al: Imaging associations of self-injurious behaviours amongst patients with borderline personality disorder: a mini-review. J Affect Disord 2021; 295:781–787
96.
Goldstein KE, Feinberg A, Corniquel MB, et al: Anomalous amygdala habituation to unpleasant stimuli among unmedicated individuals with borderline personality disorder and a history of self-harming behavior. J Pers Disord 2021; 35:618–631
97.
Olié E, Doell KC, Corradi-Dell’Acqua C, et al: Physical pain recruits the nucleus accumbens during social distress in borderline personality disorder. Soc Cogn Affect Neurosci 2018; 13:1071–1080
98.
Niedtfeld I, Schmitt R, Winter D, et al: Pain-mediated affect regulation is reduced after dialectical behavior therapy in borderline personality disorder: a longitudinal fMRI study. Soc Cogn Affect Neurosci 2017; 12:739–747
99.
Marceau EM, Meuldijk D, Townsend ML, et al: Biomarker correlates of psychotherapy outcomes in borderline personality disorder: a systematic review. Neurosci Biobehav Rev 2018; 94:166–178
100.
Herpertz SC, Schneider I, Schmahl C, et al: Neurobiological mechanisms mediating emotion dysregulation as targets of change in borderline personality disorder. Psychopathology 2018; 51:96–104
101.
Perez DL, Vago DR, Pan H, et al: Frontolimbic neural circuit changes in emotional processing and inhibitory control associated with clinical improvement following transference‐focused psychotherapy in borderline personality disorder. Psychiatry Clin Neurosci 2016; 70:51–61
102.
Schmitt R, Winter D, Niedtfeld I, et al: Effects of psychotherapy on neuronal correlates of reappraisal in female patients with borderline personality disorder. Biol Psychiatry Cogn Neurosci Neuroimaging 2016; 1:548–557
103.
Lei X, Zhong M, Zhang B, et al: Structural and functional connectivity of the anterior cingulate cortex in patients with borderline personality disorder. Front Neurosci 2019; 13:971
104.
Zimmerman M, McGonigal P, Moon SS, et al: Does diagnosing a patient with borderline personality disorder negatively impact patient satisfaction with the initial diagnostic evaluation? Ann Clin Psychiatry 2018; 30:215–219
105.
Courtney DB, Makinen J: Impact of diagnosis disclosure on adolescents with borderline personality disorder. J Can Acad Adolesc Psychiatry 2016; 25:177–184
106.
Zimmerman M, Balling C, Dalrymple K, et al: Screening for borderline personality disorder in psychiatric outpatients with major depressive disorder and bipolar disorder. J Clin Psychiatry 2019; 80:18m12257
107.
Storebø OJ, Stoffers-Winterling JM, Völlm BA, et al: Psychological therapies for people with borderline personality disorder. Cochrane Database Syst Rev 2020; 5:CD012955
108.
Arntz A, Jacob GA, Lee CW, et al: Effectiveness of predominantly group schema therapy and combined individual and group schema therapy for borderline personality disorder: a randomized clinical trial. JAMA Psychiatry 2022; 79:287–299
109.
Hawton K, Witt KG, Salisbury TL, et al: Interventions for self‐harm in children and adolescents. Cochrane Database Syst Rev 2015; 2015:CD012013
110.
Witt KG, Hetrick SE, Rajaram G, et al: Interventions for self‐harm in children and adolescents. Cochrane Database Syst Rev 2021; 3:CD013667
111.
Gunderson JG, Links P: Handbook of Good Psychiatric Management for Borderline Personality Disorder. Washington, DC, American Psychiatric Pub, 2014.
112.
Bateman AW, Krawitz R: Borderline Personality Disorder: An Evidence-Based Guide for Generalist Mental Health Professionals. Oxford, UK, Oxford University Press, 2013.
113.
Bateman A, Fonagy P: Randomized controlled trial of outpatient mentalization-based treatment versus structured clinical management for borderline personality disorder. Am J Psychiatry 2009; 166:1355–1364
114.
McMain SF, Links PS, Gnam WH, et al: A randomized trial of dialectical behavior therapy versus general psychiatric management for borderline personality disorder. Am J Psychiatry 2009; 166:1365–1374
115.
Huxley E, Lewis KL, Coates AD, et al: Evaluation of a brief intervention within a stepped care whole of service model for personality disorder. BMC Psychiatry 2019; 19:341
116.
Laporte L, Paris J, Bergevin T, et al: Clinical outcomes of a stepped care program for borderline personality disorder. Personal Ment Health 2018; 12:252–264
117.
Wilhelm K, Finch A, Kotze B, et al: The green card clinic: overview of a brief patient-centred intervention following deliberate self-harm. Australas Psychiatry 2007; 15:35–41
118.
Juul S, Lunn S, Poulsen S, et al: Short-term versus long-term mentalization-based therapy for outpatients with subthreshold or diagnosed borderline personality disorder: a protocol for a randomized clinical trial. Trials 2019; 20:196
119.
McMain SF, Chapman AL, Kuo JR, et al: The effectiveness of 6 versus 12 months of dialectical behavior therapy for borderline personality disorder: a noninferiority randomized clinical trial. Psychother Psychosom 2022; 23:1–16
120.
Stoffers-Winterling JM, Storebø OJ, Kongerslev MT, et al: Psychotherapies for borderline personality disorder: a focused systematic review and meta-analysis. Br J Psychiatry (Epub Jan 28, 2022). doi: 10.1192/bjp.2021.204
121.
Stanley B, Brodsky B, Nelson JD, et al: Brief dialectical behavior therapy (DBT-B) for suicidal behavior and non-suicidal self injury. Arch Suicide Res 2007; 11:337–341
122.
Chanen AM, Berk M, Thompson K: Integrating early intervention for borderline personality disorder and mood disorders. Harv Rev Psychiatry 2016; 24:330–341
123.
Choi-Kain LW, Albert EB, Gunderson JG, et al: Evidence-based treatments for borderline personality disorder: implementation, integration, and stepped care. Harv Rev Psychiatry 2016; 24:342–356
124.
Gregory RJ, Chlebowski S, Kang D, et al: A controlled trial of psychodynamic psychotherapy for co-occurring borderline personality disorder and alcohol use disorder. Psychotherapy (Chic) 2008; 45:28–41
125.
Majdara E, Rahimmian I, Talepassand S, et al: A randomized trial of dynamic deconstructive psychotherapy in Iran for borderline personality disorder. J Am Psychoanal Assoc 2019; 67:NP1–NP7
126.
Bohus M, Kleindienst N, Hahn C, et al: Dialectical behavior therapy for posttraumatic stress disorder (DBT-PTSD) compared with cognitive processing therapy (CPT) in complex presentations of PTSD in women survivors of childhood abuse: a randomized clinical trial. JAMA Psychiatry 2020; 77:1235–1245
127.
Guillén V, Díaz-García A, Mira A, et al: Interventions for family members and carers of patients with borderline personality disorder: a systematic review. Fam Process 2021; 60:134–144
128.
Gartlehner G, Crotty K, Kennedy S, et al: Pharmacological treatments for borderline personality disorder: a systematic review and meta-analysis. CNS Drugs 2021; 35:1053–1067
129.
Bozzatello P, Rocca P, De Rosa ML, et al: Current and emerging medications for borderline personality disorder: is pharmacotherapy alone enough? Expert Opin Pharmacother 2020; 21:47–61
130.
Bridler R, Häberle A, Müller ST, et al: Psychopharmacological treatment of 2195 in-patients with borderline personality disorder: a comparison with other psychiatric disorders. Eur Neuropsychopharmacol 2015; 25:763–772
131.
Borderline Personality Disorder: Treatment and Management. Leicester, UK, British Psychological Society, National Collaborating Centre for Mental Health, 2009
132.
Gelenberg AJ, Freeman MP, Markowitz JC, et al: American Psychiatric Association practice guidelines for the treatment of patients with major depressive disorder. Am J Psychiatry 2010; 167(suppl 10):9–118
133.
Clinical Practice Guideline for the Management of Borderline Personality Disorder. Canberra, AU, National Health and Medical Research Council, Australian Government National Health and Medical Research Council, 2012
134.
Crawford MJ, Sanatinia R, Barrett B, et al: The clinical effectiveness and cost-effectiveness of lamotrigine in borderline personality disorder: a randomized placebo-controlled trial. Am J Psychiatry 2018; 175:756–764
135.
Gunderson JG, Choi-Kain LW: Medication management for patients with borderline personality disorder. Am J Psychiatry 2018; 175:709–711
136.
Choi-Kain LW, Gunderson JG: Good Psychiatric Management for Borderline Personality Disorder [Online Course]. Harvard Medical School CME Online, 2020. https://cmeregistration.hms.harvard.edu/events/general-psychiatric-management-for-bpd/event-summary-010e9339540f40bbbe77de85d8d07d00.aspx?5S,M3,010e9339-540f-40bb. Accessed July 1, 2022
137.
Daskalakis ZJ, Dimitrova J, McClintock SM, et al: Magnetic seizure therapy (MST) for major depressive disorder. Neuropsychopharmacology 2020; 45:276–282
138.
Lisoni J, Barlati S, Deste G, et al: Efficacy and tolerability of brain stimulation interventions in borderline personality disorder: state of the art and future perspectives—a systematic review. Prog Neuropsychopharmacol Biol Psychiatry 2022; 116:110537
139.
Feffer K, Lee HH, Wu W, et al: Dorsomedial prefrontal rTMS for depression in borderline personality disorder: a pilot randomized crossover trial. J Affect Disord 2022; 301:273–280
140.
Calderón-Moctezuma AR, Reyes-López JV, Rodríguez-Valdés R, et al: Improvement in borderline personality disorder symptomatology after repetitive transcranial magnetic stimulation of the dorsomedial prefrontal cortex: preliminary results. Braz J Psychiatry 2021; 43:65–69
141.
Yip AG, Ressler KJ, Rodriguez-Villa F, et al: Treatment outcomes of electroconvulsive therapy for depressed patients with and without borderline personality disorder: a retrospective cohort study. J Clin Psychiatry 2021; 82:19m13202
142.
Lee JH, Kung S, Rasmussen KG, et al: Effectiveness of electroconvulsive therapy in patients with major depressive disorder and comorbid borderline personality disorder. J ECT 2019; 35:44–47
143.
Zimmerman M: Screening tests are not diagnostic: a commentary on a study of electroconvulsive therapy for depressed patients with and without borderline personality disorder. J Clin Psychiatry 2021; 82:21com13909
144.
Ilagan GS, Iliakis EA, Wilks CR, et al: Smartphone applications targeting borderline personality disorder symptoms: a systematic review and meta-analysis. Borderline Personal Disord Emot Dysregul 2020; 7:12
145.
Zimmerman M, Ward M, D’Avanzato C, et al: Telehealth treatment of patients with borderline personality disorder in a partial hospital setting during the COVID-19 pandemic: comparative safety, patient satisfaction, and effectiveness of in-person treatment. J Pers Disord 2022; 36:277–295

Information & Authors

Information

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History

Published in print: Fall 2022
Published online: 25 October 2022

Keywords

  1. Borderline personality disorder
  2. neuroimaging
  3. dimensional classification
  4. treatment planning
  5. psychotherapy
  6. psychopharmacology
  7. Treatment assessment & planning

Authors

Details

Lois W. Choi-Kain, M.D., M.Ed. [email protected]
Gunderson Personality Research Institute, McLean Hospital, Belmont, Massachusetts, and Faculty of Medicine, Harvard Medical School, Boston.
Zeynep Sahin, Ph.D.
Gunderson Personality Research Institute, McLean Hospital, Belmont, Massachusetts, and Faculty of Medicine, Harvard Medical School, Boston.
Jenna M. Traynor, Ph.D.
Gunderson Personality Research Institute, McLean Hospital, Belmont, Massachusetts, and Faculty of Medicine, Harvard Medical School, Boston.

Notes

Send correspondence to Dr. Choi-Kain ([email protected]).

Competing Interests

Dr. Choi-Kain receives book royalties from Springer Publishing and the American Psychiatric Association. Dr. Traynor is a coinvestigator on a Multidisciplinary Association for Psychedelic Studies (MAPS)-funded clinical trial of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy; she has also received compensation as an independent contractor for the role of study therapist on a MAPS-funded clinical trial of MDMA-assisted psychotherapy. Dr. Sahin reports no financial relationships with commercial interests.

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