or borderline ? Understanding the clinical, psychopathological, and sociodemographic correlates is critical

Sabrina Correa da Costa, MD* Fellow lthough evidence suggests that bipolar disorder (BD) and bor- Department of Psychiatry derline personality disorder (BPD) are distinct entities, their Yale University School of Medicine differential diagnosis is often challenging as a result of consid- New Haven, Connecticut A erable overlap of phenotypical features. Moreover, BD and BPD fre- Marsal Sanches, MD, PhD, FAPA Associate Professor quently co-occur, which makes it even more difficult to differentiate Research Track Residency Training Director these 2 conditions. Strategies for improving diagnostic accuracy are crit- Department of Psychiatry and Behavioral Sciences ical to optimizing patients’ clinical outcomes and long-term prognosis. The University of Texas Health Science Center at Houston McGovern Medical School Misdiagnosing these 2 conditions can be particularly deleterious, and Houston, Texas failure to recognize their co-occurrence can result in additional burden Jair C. Soares, MD, PhD to typically complex and severe clinical presentations. Professor & Chairman This article describes key aspects of the differential diagnosis between Pat R. Rutherford, Jr. Chair in Psychiatry Director, Center of Excellence on Mood Disorders BD and BPD, emphasizing core features and major dissimilarities Executive Director UTHealth HCPC between these 2 conditions, and discusses the implications of misdiag- Department of Psychiatry and Behavioral Sciences nosis. The goal is to highlight the clinical and psychopathological aspects The University of Texas Health Science Center at Houston McGovern Medical School of BD and BPD to help clinicians properly distinguish these 2 disorders. Houston, Texas

*At the time this article was written, Dr. da Costa was Chief Resident, Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, McGovern Medical School, Houston, Texas. Psychopathological and sociodemographic correlates

Disclosures Bipolar disorder is a chronic and severe mental illness that is classified Dr. Soares receives grant or research support from Compass, based on clusters of symptoms—manic, hypomanic, and depressive.1 It Pathways, Alkermes, Allergan, Merck, and Pfizer, is a consultant to Johnson & Johnson, Myriad, and LivaNova, and is a speaker for is among the 10 leading causes of disability worldwide, with significant 2 Sanofi and Sunovion. Dr. Soares is an Editorial Consultant for Current morbidity arising from acute affective episodes and subacute states. Psychiatry. Drs. da Costa and Sanches report no financial relationships Data suggest the lifetime prevalence of BPD is 2.1%, and subthreshold with any companies whose products are mentioned in this article, or 3 with manufacturers of competing products. forms may an additional 2.4% of the US population. The onset of symptoms typically occurs during late adolescence or early adulthood, É and mood lability and cyclothymic temperament are the most common prodromal features.4 continued

Current Psychiatry

LUDVIK GLAZER-NAUD Vol. 18, No. 11 27 Figure Bipolar disorder and borderline personality disorder: Clinical and sociodemographic correlates Bipolar and related disorders

Bipolar disorder 2.1% of the population 1:1.1 female/male ratio or BPD?

10% to 20% mortality from suicide

• Episodic course • Gradual changes in mood (days to weeks) • SI/SA in the context of mood symptoms Clinical Point • NSSI less common • Psychotic symptoms only in the presence of mood As a result of the symptoms phenotypical • Family history of mood disorders resemblance between • Interpersonal relationships usually preserved BD and BPD, the differential diagnosis Highly comorbid with: Treatments is often difficult • disorders • First-line: Mood stabilizers, SGAs, • ADHD AEDs, and other pharmacologic agents; ECT, rTMS, and other • Substance use disorders somatic treatments (up to 60% comorbid AUD) • Adjunctive: Psychosocial/ behavioral interventions

ADHD: -deficit/hyperactivity disorder; AEDs: antiepileptic drugs; AUD: use disorder; ECT: electroconvulsive therapy; NSSI: nonsuicidal self-injury; PTSD: posttraumatic disorder; rTMS: repetitive transcranial magnetic ; SGAs: second-generation ; SA: suicide attempt; SI: suicidal ideation

In contrast, personality disorders, such According to the National Survey on as BPD, are characteristically pervasive Alcohol and Related Conditions (NESARC), and maladaptive patterns of emotional approximately 15% of US adults were found responses that usually deviate from an to have at least one type of personality dis- individual’s stage of development and cul- order, and 6% met criteria for a cluster B tural background.1 These disorders tend personality disorder (antisocial, borderline, to cause significant impairment, particu- narcissistic, and histrionic).7 The lifetime larly in personal, occupational, and social prevalence of BPD is nearly 2%, with higher domains. Environmental factors, such as estimates observed in psychiatric settings.7,8 Discuss this article at early childhood trauma, seem to play an As a result of the phenotypical resem- www.facebook.com/ important role in the genesis of personality blance between BD and BPD (Figure), the MDedgePsychiatry disorders, which may be particularly rel- differential diagnosis is often difficult. Recent evant in BPD, a disorder characterized by studies suggest that co-occurrence of BD and marked impulsivity and a pattern of insta- BPD is common, with rates of comorbid BPD bility in personal relationships, self-image, as high as 29% in BD I and 24% in BD II.8,9 and affect.1,5,6 Similarly to BD, BPD is also On the other hand, nearly 20% of individu- Current Psychiatry 28 November 2019 chronic and highly disabling. als with BPD seem to have comorbid BD.8,9 MDedge.com/psychiatry Borderline personality disorder

1% to 2% of the population 2:1 female/male ratio

8% to 10% mortality from suicide

• Pervasive course • Abrupt changes in mood (hours) • SI/SA in the context of psychosocial stressors • NSSI common Clinical Point • Transient psychotic symptoms, usually in the context of stressful situations Evidence suggests • Chaotic interpersonal relationships that BD and BPD • Significant history of trauma have distinct underlying Highly comorbid with: Treatments neurobiological and • Mood disorders • First-line: Psychosocial/behavioral psychopathological • PTSD interventions mechanisms • Substance use • Adjunctive: Pharmacotherapy • Eating disorders

ADHD: attention-deficit/hyperactivity disorder; AEDs: antiepileptic drugs; AUD: alcohol use disorder; ECT: electroconvulsive therapy; NSSI: nonsuicidal self-injury; PTSD: posttraumatic stress disorder; rTMS: repetitive transcranial magnetic stimulation; SGAs: second-generation antipsychotics; SA: suicide attempt; SI: suicidal ideation

Several studies suggest that comorbid per- Multidimensional approaches have been sonality disorders represent a negative prog- proposed to better characterize these dis- nostic factor in the course of mood disorders, orders in at-risk populations, based on and the presence of BPD in patients with BD structured interviews, self-administered seems to be associated with more severe clini- and clinician-rated clinical scales (Table 1, cal presentations, greater treatment complex- page 35), neuroimaging studies, biological ity, a higher number of depressive episodes, markers, and machine- models.15,16 poor inter-episode functioning, and higher Compelling evidence suggests that BD and rates of other comorbidities, such as sub- BPD have distinct underlying neurobiologi- stance use disorders (SUDs).8-11 The effect of cal and psychopathological mechanisms12,13; BD on the course of BPD is unclear and fairly however, the differential diagnosis still unexplored, although it has been suggested relies on phenotypical features, since the that better control of mood symptoms may search for biological markers has not yet lead to more stable psychosocial functioning identified specific biomarkers that can be in BPD.9 used in clinical practice. Whether BD and BPD are part of the Core features of BPD, such as mood labil- Current Psychiatry same spectrum is a matter for debate.12-14 ity, impulsivity, and risk-taking behaviors, Vol. 18, No. 11 29 continued on page 35 continued from page 29

Table 1 Clinical scales used in the differential diagnosis of bipolar disorder

and borderline personality disorder MDedge.com/psychiatry Rating scale Description Questionnaire 15 questions (MDQ) The first 13 questions are designed to identify lifetime manic or hypomanic symptoms; the last 2 questions measure severity and level of functional impairment / Checklist 2 introductory questions on current emotional state (HCL-32) 32 questions designed to identify manic and hypomanic symptoms Screening Assessment of 3-item scale: -Polarity (SAD-P) • presence of • number of depressive episodes • family history of major depression or mania Bipolar Prodrome Symptom Semi-structured interview developed based on DSM-IV criteria Interview and Scale-Prospective for BD and MDD, clusters of symptoms (mania, depression, and (BPSS-P) general symptom index) Clinical Point The Personality Inventory for 220-item scale assessing 25 personality trait facets, with each trait DSM-5 facet consisting of 4 to 14 items combined in 5 broader domains: Comprehensive • negative affect • detachment psychiatric • antagonism assessments • disinhibition • psychoticism and longitudinal Structured Clinical Interview As an updated version of the SCID-Axis II Personality Disorder observations are for DSM-5 Personality Disorder Questionnaire from DSM-IV, the SCID-5-PD consists of objective (SCID-5-PD) and self-reported components that can be used in research critical to diagnostic and clinical practice to identify the different PDs across clusters accuracy A, B, and C. Borderline Symptom List 23 23-item scale assessing severity of symptoms (from 0 = not (BSL-23) at all to 4 = very strong) in the previous week in addition to 10 supplemental items to assess behaviors McLean Screening Instrument for 10-item clinical scale (YES or NO answers) based on DSM-IV Borderline Personality Disorder criteria for BPD (MSI-BPD) Borderline Personality Disorder Clinical scale based on DSM-IV criteria for BPD designed to Severity Index-IV assess the presence and severity of BPD symptoms BD: bipolar disorder; BPD: borderline personality disorder; MDD: major depressive disorder; PDs: personality disorders

are also part of the diagnostic criteria for and impulsivity are part of a mood or a per- BD (Table 2, page 36).1 Similarly, depres- sonality disorder (Table 3, page 37). sive symptoms prevail in the course of BD.17,18 This adds complexity to the differ- ential because “depressivity” is also part of Clinical features: A closer look the diagnostic criteria for BPD.1 Therefore, Borderline personality disorder. Affect dys- comprehensive psychiatric assessments regulation, emotional instability, impover- and longitudinal observations are critical ished and unstable self-image, and chronic to diagnostic accuracy and treatment plan- of are core features of ning. Further characterization of symptoms, BPD.1,5,19 These characteristics, when com- such as onset patterns, clinical course, phe- bined with a of abandonment or rejec- nomenology of symptoms (eg, timing, fre- tion, a compromised ability to recognize the quency, duration, triggers), and personality feelings and needs of others, and extremes traits, will provide to properly of idealization-devaluation, tend to culmi- distinguish these 2 syndromes when, for nate in problematic and chaotic relation- Current Psychiatry example, it is unclear if the “mood swings” ships.6,19 Individuals with BPD may become Vol. 18, No. 11 35 Table 2 Core features of bipolar disorder vs borderline personality disorder Bipolar disorder Borderline personality disorder Depressive symptoms Impairment in personality functioning • depressed mood • impoverished or unstable self-image • sad, empty, or hopeless • excessive self-criticism • diminished or in activities • chronic feelings of emptiness Bipolar disorder • significant weight loss or gain • dissociative states under stress • or • compromised ability to recognize the feelings or BPD? • or retardation and needs of others • feelings of worthlessness or excessive • of others selectively biased • indecisiveness or poor concentration • intense, unstable and conflicted relationships • recurrent thoughts of death or suicide • extremes of idealization-devaluation • suicidal ideations, plans, or intent Manic/hypomanic symptoms Pathological personality traits • elevated, expansive, or irritable mood • and anxiousness • increased goal-directed activity • feelings of falling apart or losing control • high risk-taking behaviors • fear of abandonment/rejection Clinical Point • or inflated self-esteem • depressivity: feelings of being down, • decreased need for sleep hopeless, or miserable Fluctuations in mood • increased energy • , pervasive , and inferior • distractibility self-worth in patients with BD • impulsivity • thoughts of suicide, suicidal gestures, • psychomotor agitation and NSSI behaviors tend to last days to • pressured speech • impulsivity and disinhibition weeks, in contrast to • flight of ideas • high risk-taking behaviors • and antagonism the transient mood NSSI: nonsuicidal self-injury shifts of patients with BPD

suspicious or paranoid under stressful situa- of comorbid mood disorders, posttraumatic tions. Under these circumstances, individuals stress disorder (PTSD), SUDs, and death with BPD may also experience deperson- by suicide. alization and other dissociative symptoms.6,20 The mood lability and emotional instability Bipolar disorder. Conversely, the fluctua- observed in patients with BPD usually are tions in mood and affect observed in patients in response to environmental factors, and with BD are usually episodic rather than although generally intense and out of pro- pervasive, and tend to last longer (typically portion, they tend to be ephemeral and short- days to weeks) compared with the tran- lived, typically lasting a few hours.1,5 The sient mood shifts observed in patients with anxiety and depressive symptoms reported BPD.4,17,18 The impulsivity, psychomotor by patients with BPD frequently are associ- agitation, and increased goal-directed activ- ated with feelings of “falling apart” or “los- ity reported by patients with BD are usu- ing control,” pessimism, shame, and low ally seen in the context of an acute affective self-esteem. strategies tend to be episode, and are far less common during poorly developed and/or maladaptive, and periods of stability or euthymic affect.4,17,18 individuals with BPD usually display a hos- Grandiosity and inflated self-esteem—hall- tile and antagonistic demeanor and engage marks of a manic or hypomanic state—seem in suicidal or non­suicidal self-injury (NSSI) to oppose the unstable self-image observed behaviors as means to alleviate overwhelm- in BPD, although indecisiveness and low ing emotional distress. Impulsivity, disin- self-worth may be observed in individu- hibition, poor tolerance to , and als with BD during depressive episodes. risk-taking behaviors are also characteristic Antidepressant-induced mania or hypo- of BPD.1,5 As a result, BPD is usually associ- mania, atypical depressive episodes, and ated with significant impairment in function- disruptions in sleep and circadian rhythms Current Psychiatry 36 November 2019 ing, multiple hospitalizations, and high rates may be predictors of BD.4,21 Furthermore, although psychosocial stressors may be Table 3 associated with acute affective episodes History-taking: Specific clinical in early stages of bipolar illness, over time and psychopathological features minimal stressors are necessary to ignite MDedge.com/psychiatry new affective episodes.22,23 Although BD is Clinical and psychopathological features associated with high rates of suicide, sui- Phenomenology of symptoms: • onset patterns cide attempts are usually seen in the context • timing/duration of an acute depressive episode, and NSSI • frequency behaviors are less common among patients • triggers with BD.24 Longitudinal course: episodic vs pervasive Lastly, other biographical data, such as Comorbidity a history of early life trauma, comorbidity, History of childhood adversity and a family history of psychiatric illnesses, Early life trauma can be particularly helpful in establish- Nonsuicidal self-injury behaviors ing the differential diagnosis between BD Pathological personality traits 25 and BPD. For instance, evidence suggests Interpersonal relationship patterns that the heritability of BD may be as high Family history of psychiatric disorders Clinical Point as 70%, which usually translates into an Nonsuicidal self- extensive family history of bipolar and related disorders.26 In addition, studies injury behaviors are suggest a high co-occurrence of anxiety behavioral interventions are the mainstay common in patients disorders, attention-deficit/hyperactivity treatment for this disorder, with the strongest with BPD but less so disorder, and SUDs in patients with BD, evidence supporting cognitive-behavioral in those with BD whereas PTSD, SUDs, and eating disorders therapy, dialectical behavioral therapy, men- tend to be highly comorbid with BPD.27 talization-based therapy, and transference- Childhood adversity (ie, a history of physi- focused therapy.34-36 Thus, misdiagnosing BD cal, sexual, or emotional abuse, or ) as BPD with comorbid depression may result seems to be pivotal in the genesis of BPD in the use of antidepressants, which can be and may predispose these individuals detrimental in BD. Antidepressant treatment to psychotic and dissociative symptoms, of BD, particularly as monotherapy, has particularly those with a history of sexual been associated with manic or hypomanic abuse, while playing a more secondary switch, mixed states, and frequent cycling.21 role in BD.28-31 Moreover, delays in diagnosis and proper treatment of BD may result in protracted mood symptoms, prolonged affective epi- Implications of misdiagnosis sodes, higher rates of disability, functional In the view of the limitations of the exist- impairment, and overall worse clinical out- ing models, multidimensional approaches comes.24 In addition, because behavioral are necessary to improve diagnostic accu- and psychosocial interventions are usually racy. Presently, the differential diagnosis adjunctive therapies rather than first-line of BD and BPD continues to rely on clini- interventions for patients with BD, misdiag- cal findings and syndromic classifications. nosing BPD as BD may ultimately prevent Misdiagnosing BD and BPD has adverse these individuals from receiving proper therapeutic and prognostic implications.32 treatment, likely resulting in more severe For instance, while psychotropic medica- functional impairment, multiple hospital- tions and neuromodulatory therapies (eg, izations, self-inflicted injuries, and suicide electroconvulsive therapy, repetitive tran- attempts, since psychotropic medications scranial magnetic stimulation) are consid- are not particularly effective for improving ered first-line treatments for patients with self-efficacy and coping strategies, nor for BD, psychosocial interventions tend to be correcting cognitive distortions, particularly adjunctive treatments in BD.33 Conversely, in self-image, and pathological personal- although pharmacotherapy might be help- ity traits, all of which are critical aspects of Current Psychiatry ful for patients with BPD, psychosocial and BPD treatment. Vol. 18, No. 11 37 continued Several factors might make clinicians reluctant to diagnose BPD, or bias them to Related Resources diagnose BD more frequently. These include • Fiedorowicz JG, Black DW. Borderline, bipolar, or both? Frame your diagnosis on the patient history. Current Psychiatry. 2010; a lack of familiarity with the diagnostic cri- 9(1):21-24,29-32. teria for BPD, the phenotypical resemblance • Zimmerman M. Improving the recognition of borderline between BP and BPD, or even concerns about personality disorder. Current Psychiatry. 2017;16(10):13-19. the stigma and negative implications that are • National Institute of . Overview on bipolar disorder. www.nimh.nih.gov/health/publications/bipolar- 32,37,38 Bipolar disorder associated with a BPD diagnosis. disorder/index.shtml. Revised October 2018. or BPD? Whereas BD is currently perceived as • National Institute of Mental Health. Overview on borderline a condition with a strong biological basis, personality disorder. www.nimh.nih.gov/health/publications/ borderline-personality-disorder-fact-sheet/index.shtml. there are considerable misconceptions regarding BPD and its nature.4-6,22,26 As a consequence, individuals with BPD tend to be perceived as “difficult-to-treat,” “unco- operative,” or “attention-seeking.” These 4. Malhi GS, Bargh DM, Coulston CM, et al. Predicting bipolar disorder on the basis of phenomenology: implications misconceptions may result in poor clini- for prevention and early intervention. Bipolar Disord. Clinical Point cian-patient relationships, unmet clinical 2014;16(5):455-470. 5. Skodol AE, Gunderson JG, Pfohl B, et al. The borderline Misdiagnosing BD as and psychiatric needs, and frustration for diagnosis I: . Biol Psychiatry. 2002;51(12): both clinicians and patients.37 936-950. BPD with comorbid 6. Skodol AE, Siever LJ, Livesley WJ, et al. 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Bottom Line Despite the phenotypical resemblance between bipolar disorder (BP) and borderline personality disorder (BPD), the 2 are independent conditions with distinct neurobiological and psychopathological underpinnings. Clinicians can use a rigorous assessment of pathological personality traits and characterization of symptoms, such as onset patterns, clinical course, and phenomenology, to properly Current Psychiatry 38 November 2019 distinguish between BP and BPD. 15. Perez Arribas I, Goodwin GM, Geddes JR, et al. A signature- 26. Hasler G, Drevets WC, Gould TD, et al. Toward constructing based machine learning model for distinguishing bipolar an endophenotype strategy for bipolar disorders. Biol disorder and borderline personality disorder. Transl Psychiatry. 2006;60(2):93-105. Psychiatry. 2018;8(1):274. 27. Brieger P, Ehrt U, Marneros A. Frequency of comorbid 16. Insel T, Cuthbert B, Garvey M, et al. Research Domain personality disorders in bipolar and unipolar affective Criteria (RDoC): toward a new classification framework disorders. Compr Psychiatry. 2003;44(1):28-34. MDedge.com/psychiatry for research on mental disorders. Am J Psychiatry. 2010; 28. Leverich GS, McElroy SL, Suppes T, et al. Early physical and 167(7):748-751. sexual abuse associated with an adverse course of bipolar 17. Judd LL, Akiskal HS, Schettler PJ, et al. The long-term illness. Biol Psychiatry. 2002;51(4):288-297. natural history of the weekly symptomatic status of 29. Leverich GS, Post RM. Course of bipolar illness after history bipolar I disorder. Arch Gen Psychiatry. 2002;59(6): of childhood trauma. Lancet. 2006;367(9516):1040-1042. 530-537. 30. Golier JA, Yehuda R, Bierer LM, et al. The relationship 18. Judd LL, Akiskal HS, Schettler PJ, et al. A prospective of borderline personality disorder to posttraumatic investigation of the natural history of the long-term stress disorder and traumatic events. Am J Psychiatry. weekly symptomatic status of bipolar II disorder. Arch Gen 2003;160(11):2018-2024. Psychiatry. 2003;60(3):261-269. 31. Nicol K, Pope M, Romaniuk L, et al. Childhood trauma, 19. Oldham JM, Skodol AE, Bender DS. A current integrative midbrain activation and psychotic symptoms in borderline perspective on personality disorders. American Psychiatric personality disorder. Transl Psychiatry. 2015;5:e559. Publishing, Inc. 2005. doi:10.1038/tp.2015.53. 20. Herzog JI, Schmahl C. Adverse childhood experiences and 32. Ruggero CJ, Zimmerman M, Chelminski I, et al. Borderline the consequences on neurobiological, psychosocial, and personality disorder and the misdiagnosis of bipolar somatic conditions across the lifespan. Front Psychiatry. disorder. J Psychiatr Res. 2010;44(6):405-408. 2018;9:420. 33. Geddes JR, Miklowitz DJ. Treatment of bipolar disorder. 21. Barbuti M, Pacchiarotti I, Vieta E, et al. Antidepressant- Lancet. 2013;381(9878):1672-1682. induced hypomania/mania in patients with major 34. McMain S, Korman LM, Dimeff L. Dialectical behavior Clinical Point depression: evidence from the BRIDGE-II-MIX study. J therapy and the treatment of dysregulation. J Clin Affect Disord. 2017;219:187-192. Psychol. 2001;57(2):183-196. Destigmatizing 22. Post RM. Mechanisms of illness progression in the 35. Cristea IA, Gentili C, Cotet CD, et al. Efficacy of recurrent affective disorders. Neurotox Res. 2010;18(3-4): psychotherapies for borderline personality disorder: a psychiatric disorders 256-271. systematic review and meta-analysis. JAMA Psychiatry. 23. da Costa SC, Passos IC, Lowri C, et al. Refractory 2017;74(4):319-328. and educating bipolar disorder and neuroprogression. Prog Neuro- 36. Linehan MM, Korslund KE, Harned MS, et al. Dialectical Psychopharmacology Biol Psychiatry. 2016;70:103-110. behavior therapy for high suicide risk in individuals patients and 24. Crump C, Sundquist K, Winkleby MA, et al. Comorbidities with borderline personality disorder. JAMA Psychiatry. and mortality in bipolar disorder: a Swedish national cohort 2015;72(75);475-482. clinicians are key to study. JAMA Psychiatry. 2013;70(9):931-939. 37. LeQuesne ER, Hersh RG. Disclosure of a diagnosis 25. Zimmerman M, Martinez JH, Morgan TA, et al. of borderline personality disorder. J Psychiatr Pract. improving clinical Distinguishing bipolar II depression from major depressive 2004:10(3):170-176. disorder with comorbid borderline personality disorder: 38. Young AH. Bipolar disorder: diagnostic conundrums and outcomes demographic, clinical, and family history differences. J Clin associated comorbidities. J Clin Psychiatry. 2009;70(8):e26. Psychiatry. 2013;74(9):880-886. doi:10.4088/jcp.7067br6c.

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