Differences between patients with borderline personality disorder who do and do not have a family history of bipolar disorder

    Differences between Patients with Borderline Personality Disorder who Do and Do Not Have a Family History of Bipolar Disorder Mark Zimmerman, Jennifer Martinez, Diane Young, Iwona Chelminski, Kristy Dalrymple PII: DOI: Reference:

S0010-440X(14)00130-8 doi: 10.1016/j.comppsych.2014.05.012 YCOMP 51317

To appear in:

Comprehensive Psychiatry

Received date: Revised date: Accepted date:

11 April 2014 19 May 2014 20 May 2014

Please cite this article as: Zimmerman Mark, Martinez Jennifer, Young Diane, Chelminski Iwona, Dalrymple Kristy, Differences between Patients with Borderline Personality Disorder who Do and Do Not Have a Family History of Bipolar Disorder, Comprehensive Psychiatry (2014), doi: 10.1016/j.comppsych.2014.05.012

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Differences between Patients with Borderline Personality Disorder who Do and Do Not

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Have a Family History of Bipolar Disorder

Mark Zimmerman, M.D.

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Jennifer Martinez, B.A.

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Diane Young, Ph.D.

Kristy Dalrymple, Ph.D.

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Iwona Chelminski, Ph.D.

Submitted to Comprehensive Psychiatry: April 11, 2014 Submitted to Comprehensive Psychiatry: May 19, 2014

From the Department of Psychiatry and Human Behavior, Brown Medical School, Providence, RI. Address reprint requests to Mark Zimmerman, M.D, 146 West River Street, Providence, RI 02904; E-mail: [email protected]

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Abstract Diagnostic confusion sometimes exists between bipolar disorder and borderline personality

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disorder (BPD). To improve the recognition of bipolar disorder researchers have identified

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nondiagnostic factors that point towards bipolar disorder. One such factor is the presence of a family history of bipolar disorder. In the current report from the Rhode Island Methods to Improve

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Diagnostic Assessment and Services (MIDAS) project, we compared the demographic, clinical,

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and psychosocial characteristics of patients with BPD who did and did not have a family history of bipolar disorder. A large sample of psychiatric outpatients were interviewed with semi-structured

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interviews. Three hundred seventeen patients without bipolar disorder were diagnosed with DSMIV borderline personality disorder. Slightly less than 10% of the 317 patients with BPD (9.5%,

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n=30) reported a family history of bipolar disorder in their first degree relatives. There were no

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differences between groups in any specific Axis I or Axis II disorder. The patients with a positive family history were significantly less likely to report excessive or inappropriate anger, but there

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was no difference in the frequency of other criteria for BPD such as affective instability,

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impulsivity, or suicidal behavior. The patients with a positive family history reported a significantly higher rate of increased appetite and fatigue. There was no difference in overall severity of depression, scores on the Global Assessment of Functioning, history of psychiatric hospitalizations, suicide attempts, time unemployed due to psychiatric reasons during the 5 years before the evaluation, and ratings of current and adolescent social functioning. There was no difference on any of the 5 subscales of the childhood trauma questionnaire. Overall, we found few differences between BPD patients with and without a family history of bipolar disorder thereby suggesting that a positive family history of bipolar disorder was not a useful marker for occult bipolar disorder in these patients.

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1. Introduction The goal of the present investigation is to determine whether patients with borderline

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personality disorder (BPD) with a first-degree relative with bipolar disorder differ from BPD

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patients without a first-degree relative with bipolar disorder. If so, this might suggest occult bipolar disorder in the patients with a positive family history.

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The underrecognition and underdiagnosis of bipolar disorder is a significant clinical

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problem [1-4]. For patients diagnosed with bipolar disorder, the lag between initial treatment seeking and the correct diagnosis is often more than 10 years [5]. The potential clinical

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implications of underdiagnosing bipolar disorder in depressed patients include the underprescription of mood stabilizing medications, an increased risk of rapid cycling, and

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increased costs of care [2,6,7]. Experts have called for improved recognition of bipolar disorder

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because of these individual and public health consequences [1,3]. The relationship between bipolar disorder and BPD has been the subject of some

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controversy. The relatively high frequency of diagnostic co-occurrence and resemblance of some

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phenomenological features has led some authors to suggest that BPD is part of the bipolar spectrum [8,9]. In fact, in a recent large-scale international study, BPD comorbidity was considered as one of the variables validating the distinction between bipolar and nonbipolar disorder [4]. Several review articles have summarized the evidence in support of and opposition to the hypothesis that BPD belongs to the bipolar spectrum [10-13]. Diagnostic confusion sometimes exists between the two disorders [11,12,14]. Given the superficial resemblance of some of the clinical characteristics of bipolar disorder and BPD, it is not surprising that the two disorders frequently co-occur. Paris et al., [11] comprehensively reviewed studies reporting the rates of comorbidity between bipolar disorder and BPD. In 12 studies of the frequency of bipolar disorder in patients with BPD, they found that approximately 10% of the

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patients with BPD were diagnosed with bipolar I disorder and approximately 10% were diagnosed with bipolar II disorder. In 16 studies of BPD disorder co-occurrence in patients with bipolar

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disorder, approximately 10% of the patients with bipolar I disorder and 16% of patients with

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bipolar II disorder were diagnosed with BPD.

To improve the recognition of bipolar disorder researchers have identified nondiagnostic

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factors that point towards bipolar disorder. One such factor is the presence of a family history of

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bipolar disorder. That is, clinicians are encouraged to consider that a patient has occult bipolar disorder if there is a family history of bipolar disorder. In fact, Young and Klerman [15]

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considered individuals with a family history of bipolar disorder to have a variant of the disorder (bipolar type 5), and Ghaemi et al. list a positive family history of bipolar disorder as one of their

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criteria for bipolar spectrum disorder [16].

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Researchers have used a family history of bipolar disorder to validate the concept of the bipolar spectrum [4,17,18]. Although family studies of borderline personality disorder have not

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found an elevated rate of bipolar disorder in first-degree relatives [19-23], this does not preclude

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the value of using a family history of bipolar disorder in patients with borderline personality disorder to identify individuals who are on the bipolar spectrum. Accordingly, in the current report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project we compared the demographic, clinical, and psychosocial characteristics of patients with borderline personality disorder who did and did not have a family history of bipolar disorder.

2. Methods The Rhode Island MIDAS project represents an integration of research methodology into a community-based outpatient practice affiliated with an academic medical center [24]. A comprehensive diagnostic evaluation is conducted upon presentation for treatment. This private

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practice group predominantly treats individuals with medical insurance (including Medicare but not Medicaid) on a fee-for-service basis, and it is distinct from the hospital’s outpatient residency

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training clinic that predominantly serves lower income, uninsured, and medical assistance patients.

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Data on referral source was recorded for the last 1800 patients enrolled in the study. Patients were most frequently referred from primary care physicians (29.6%), psychotherapists (16.6%), and

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family members or friends (18.4%). The Rhode Island Hospital institutional review committee

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approved the research protocol, and all patients provided informed, written consent. The sample examined in the present report was derived from the 3,600 psychiatric

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outpatients evaluated with semi-structured diagnostic interviews. Patients were interviewed by a diagnostic rater who administered a modified version of the Structured Clinical Interview for

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DSM-IV (SCID) [25] supplemented with items from the Schedule for Affective Disorders and

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Schizophrenia (SADS) [26] and the BPD section of the Structured Interview for DSM-IV Personality (SIDP-IV) [27]. During the course of the MIDAS project the assessment battery has

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been modified at times. The assessment of all DSM-IV personality disorders was not introduced

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until the study was well underway and the procedural details of incorporating research interviews into our clinical practice had been well established, though we had introduced the assessment of BPD near the beginning of the study. In June, 2008 we stopped administering the full SIDP-IV and continued to only administer the BPD module. The assessment of personality disorders always followed the evaluation of Axis I disorders. In some instances, due to a lack of time, the personality disorder interview was not completed; thus, 3,465 patients were assessed for BPD, of whom 375 (10.4%) met DSM-IV criteria for BPD. We excluded the 58 patients diagnosed with both BPD and bipolar disorder because we were interested in whether BPD in the absence of bipolar disorder should be considered as part of the bipolar spectrum. This left a final sample of 317 patients with BPD without bipolar disorder who were included in the analysis. The 317

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patients included 89 (28.1%) men and 228 (71.9%) women who ranged in age from 18 to 68 years (mean = 32.1, SD =10.4). About half of the subjects were single and had never married (46.7%,

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n=148); the remainder were married (23.0%, n=73), divorced (13.9%, n=44), separated (4.4%,

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n=14), widowed (0.6%, n=2), or living with someone as if in a marital relationship (11.4%, n=36). Approximately three-quarters of the patients graduated high school (73.2%, n=232), though only a

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minority graduated a 4-year college (16.7%, n=53). The racial composition of the sample was

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86.4% (n=274) white, 6.9% (n=22) black, 3.8% (n=12) Hispanic, 1.3% (n=4) Asian, and 1.6% (n=5) from another or a combination of the above racial backgrounds.

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Following the SCID interview patients completed a booklet of questionnaires that included the Childhood Trauma Questionnaire [28]. We compared the groups on the 5 subscales of the

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neglect and emotional neglect.

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Childhood Trauma Questionnaire—emotional abuse, physical abuse, sexual abuse, physical

From the SADS we examined the items assessing psychic and somatic anxiety, anger and

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irritability, and somatization. The SADS ratings referred to symptom severity during the past

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week. The interview also included items from the SADS on best level of social functioning during the past five years, social functioning during adolescence, and the amount of time employed during the past five years. The Clinical Global Index (CGI) of depression severity [29] and Global Assessment of Functioning (GAF) were rated on all patients. The SCID/SADS interview included an assessment of lifetime number of psychiatric hospitalization and suicide attempts. Family history diagnoses were based on information provided by the patient. The interview followed the guide provided in the Family History Research Diagnostic Criteria (FH-RDC) [30] and assessed the presence or absence of problems with anxiety, mood, substance use, and other disorders for all first-degree family members.

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The diagnostic raters were highly trained and monitored throughout the project to minimize rater drift. The diagnostic raters included Ph.D. level psychologists and research assistants with

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college degrees in the social or biological sciences. Research assistants received three to four

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months of training during which they observed at least 20 interviews, and they were observed and supervised in their administration of more than 20 evaluations. Psychologists only observed 5

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interviews, and they were observed and supervised in their administration of 15 to 20 evaluations.

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During the course of training the senior author met with each rater to review the interpretation of every item on the SCID. Also during training every interview was reviewed on an item-by-item

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basis by the senior rater who observed the evaluation, and by the senior author who reviewed the case with the interviewer. At the end of the training period the raters were required to demonstrate

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exact, or near exact, agreement with a senior diagnostician on five consecutive evaluations.

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Throughout the MIDAS project, ongoing supervision of the raters consisted of weekly diagnostic

senior author.

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case conferences involving all members of the team. In addition, every case was reviewed by the

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Reliability was examined in 65 patients. A joint-interview design was used in which one rater observed another conducting the interview, and both raters independently made their ratings. For disorders diagnosed in at least two patients by at least one of the two raters the Kappa coefficients were: major depressive disorder (k=0.90, n=23), dysthymic disorder (k=0.88, n=5), bipolar disorder (k=0.75, n=8), panic disorder (k = 0.95, n=12), social phobia (k=0.84, n=19), obsessive compulsive disorder (k=1.0, n=6), specific phobia (k=0.93, n=9), generalized anxiety disorder (k=0.85, n=14), posttraumatic stress disorder (k=0.87, n=10), alcohol abuse/dependence (k=0.64, n=8), drug abuse/dependence (k=0.64, n=6), and any somatoform disorder (k=1.0, n=5). The reliability for diagnosing BPD (k=1.0) was excellent. The reliabilities of any PD (k = 0.90) any Cluster A (k = 0.79), B (k = 0.79), or C PD (k = 0.93) were good to excellent. Too few patients

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were diagnosed with other individual PDs to calculate Kappa coefficients. However, intraclass correlation coefficients (ICC) of criterion count dimensional scores were high (paranoid, ICC =

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0.92; schizoid, ICC = 0.95; schizotypal, ICC=0.82; antisocial, ICC = 0.95; borderline, ICC = 0.95;

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histrionic, ICC = 0.91; narcissistic, ICC = 0.91; avoidant, ICC = 0.96; dependent, ICC = 0.97;

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obsessive compulsive, ICC=0.90).

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Statistical Analysis

We compared the demographic and clinical characteristics of patients with DSM-IV BPD

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who did and did not have a family history of bipolar disorder. T-tests were used to compare the groups on continuously distributed variables. Categorical variables were compared by the chi-

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square statistic, or by Fisher’s Exact Test if the expected value in any cell of a 2x2 table was less

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3. Results

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than 5.

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Slightly less than 10% of the 317 (9.5%, n=30) patients with BPD reported a family history of bipolar disorder in their first degree relatives. While the majority of all patients were female, the patients with a family history of bipolar disorder were significantly more likely to be female (Table 1). There was no difference in marital status, education level, or age. High rates of diagnostic comorbidity characterized both groups. Approximately two-thirds of the patients of both groups had 3 or more current Axis I disorders. There were no differences between groups in any specific Axis I or Axis II disorder (Table 2). We compared the frequency of each BPD criterion in the 2 groups (Table 3). There was no difference in the rates of criteria that might be most closely associated with bipolar disorder--

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affective instability, impulsivity, or suicidal behavior. The patients with a positive family history were significantly less likely to report excessive or inappropriate anger.

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The patients with a positive family history reported a significantly higher rate of increased

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appetite and fatigue (Table 4). There was no difference in overall severity of depression on the CGI-S (3.0 + 1.0 vs. 2.8 + 1.0, t=0.95, n.s.). There was also no difference between the groups on

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GAF scores at the time of the evaluation (46.8 + 9.1 vs. 46.6 + 9.1, t=0.10, n.s.), and history of

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psychiatric hospitalizations, suicide attempts, time unemployed due to psychiatric reasons during the 5 years before the evaluation, and ratings of current and adolescent social functioning on the

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SADS. There was no difference on any of the 5 subscales of the childhood trauma questionnaire.

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4. Discussion

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A family history of bipolar disorder has been considered an indicator of bipolar spectrum disorder amongst patients who themselves do not report a history of manic or hypomanic episodes

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[15,16]. Some experts consider BPD to be part of the bipolar spectrum, though reviews of the

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BPD--bipolar link have reached contrasting conclusions [10-13]. In the present study we examined whether a family history of bipolar disorder amongst patients with BPD would be associated with other indicators of bipolar spectrum disorder. We found few differences between BPD patients with and without a family history of bipolar disorder. If a positive family history of bipolar disorder was a marker for bipolar spectrum disorder we might have expected that other indicators of bipolar disorder would characterize this group. However, we did not find differences in the BPD criteria that might be more characteristic of bipolar disorder such as affective instability and impulsivity. We did not find differences in rates of anxiety, substance use, or impulse control disorders that have been found to be elevated in patients with bipolar disorder [31]. We did not find differences in suicidal ideation or history of

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suicide attempts. And we did not find higher rates of childhood trauma or posttraumatic stress disorder in the patients without a positive family history of bipolar disorder. The one difference

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that we found that supported the bipolar spectrum hypothesis was a higher rate of increased

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appetite in the patients a positive family history. Other researchers have found that reverse vegetative symptoms are more frequent in patients with bipolar disorder [32-34]. Overall, then, our

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results suggest that a positive family history of bipolar disorder in patients with BPD should not be

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taken as presumptive evidence that the patient has occult bipolar disorder. While the present study did not examine treatment, the implication is that the presence of a family history of bipolar

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disorder in patients with borderline personality disorder is not sufficient to warrant treatment with mood stabilizer medication.

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The limitations of the study should be considered. The sample of patients with a positive

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family history of bipolar disorder was relatively small, thus the mostly negative findings might have been due to a lack of statistical power to detect significant differences between the groups.

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However, there was no evidence that nonsignificant trends were in the direction supporting the

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validity of a positive family history as a marker of bipolar spectrum disorder. While we examined a number of indicators of bipolar spectrum disorder such as rates of anxiety and substance use disorders and reverse vegetative features of depression we were limited in our investigation to observable phenomena. We did not examine other important validators such as longitudinal course or treatment response. It is possible that patients with a family history of bipolar disorder would have a superior response to mood stabilizers or be more likely to develop a manic or hypomanic episode during longitudinal follow-up. Also, we could not compare groups on biomarkers for bipolar disorder as none exist at the present time. A family history of bipolar disorder was ascertained using the family history method of assessment. We did not directly interview the first-degree family members of the patients.

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Compared to direct interviews of family members, the family history method has relatively low sensitivity but high specificity [35,36]. While the family history method is not as valid as direct

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interviews of family members, other reports from our group have shown that this method of

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ascertaining information was useful as a diagnostic validator [37,38]. Moreover, clinicians typically use the family history approach towards eliciting information about a family history of

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psychopathology thus these results are more relevant to usual clinical practice.

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Finally, the study was conducted in a single site in which the majority of patients were white, high school graduates, who had health insurance. However, it is not clear why a family

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history of bipolar disorder would be a less valid indicator of the bipolar spectrum in our sample

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than in samples with different demographic characteristics.

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4 18 8

13.3 60.0 26.7

28 214 45

9 5 1 1 6 8 Mean 35.8

30.0 16.7 3.3 3.3 20.0 26.7 SD 13.5

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64 31 1 13 38 140 Mean 31.8

2

P

5.36

.02

9.8 74.6 15.7

3.09

.21

22.3 10.8 0.3 4.5 13.2 48.8 SD 10.0

9.19

.10

t 1.59

p .12

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86 201

30.0 70.0

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10.0 90.0

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Age

3 27

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Gender Male Female Education Less than high school Graduated high school Graduated college Marital status Married Living with someone Widowed Separated Divorced Never married

Family History Negative (n=287) N %

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Family History Bipolar Disorder (n=30) N %

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Table 1 Demographic Characteristics in Psychiatric Outpatients with Borderline Personality Disorder with and without a Family History of Bipolar Disorder

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a

2

p

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Family History Negative (n=287) N %

.04 .21 .07

.84 1.00 .79

63.3 10.0 66.7

187 37 198

11 11 14 8 5

36.7 36.7 46.7 26.7 16.7

75 65 137 75 34

26.1 22.6 47.7 26.1 11.8

1.53 2.93 .01 .00 .59

.22 .09 .91 .95 .39

10 27

33.3 90.0

89 241

31.0 84.0

.07 .76

.79 .60

13.3 3.3 16.7 16.4 20.0 3.3 63.3

55 39 77 41 43 7 191

19.2 13.6 26.8 14.3 15.0 2.4 66.6

.61 2.59 1.46 .12 .52 .09 .13

.44 .11 .23 .78 .43 .55 .72

11.1 0.0 0.0 0.0 0.0 0.0 22.2 11.1 16.7 44.4 16.7

26 2 3 12 5 9 38 14 15 82 29

16.8 1.3 1.9 7.7 3.2 5.8 24.5 9.0 9.7 52.9 18.7

.38 .24 .36 1.50 .60 1.10 .05 .08 .85 .46 .05

.74 1.00 1.00 .62 1.00 .60 1.00 .68 .36 .50 1.00

2 0 0 0 0 0 4 2 3 8 3

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4 1 5 5 6 1 19

65.2 12.9 69.0

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19 3 20

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Disorder Mood Disorders Major depressive disorder Dysthymic disorder Any depressive disorder Anxiety Disorders Panic w/ or w/out agoraphobia Specific Phobia Social Phobia Posttraumatic stress disorder Obsessive compulsive disorder Generalized anxiety disorder Any Anxiety Disorder Substance use disorders Alcohol abuse/dependence Drug abuse/dependence Any substance use disorder Any Eating Disorder Any Somatoform Disorder Any Impulse Control Disorder Three or more Axis I disorders Personality disorders a Paranoid Schizoid Schizotypal Antisocial Histrionic Narcissistic Avoidant Dependent Obsessive-compulsive Any personality disorder Two or more personality disorders

Family History Bipolar Disorder (n=30) N %

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Table 2 Frequency of Current DSM-IV Axis I and Axis II Disorders in Psychiatric Outpatients with Borderline Personality Disorder with and without a Family History of Bipolar Disorder

The assessment of all DSM-IV personality disorders was conducted in 18 patients with a positive family history and 155 with a negative family history.

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Table 3 Borderline Personality Disorder Criteria in Psychiatric Outpatients with Borderline Personality Disorder with and without a Family History of Bipolar Disorder

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% 33.1 76.7 72.5 65.9 53.7 93.0 76.7 85.4 50.9

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N 95 220 208 189 154 267 220 245 146

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Family History Negative (n=287)

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Criterion Abandonment fear Interpersonal instability Identity disturbance Impulsive behavior Suicidal/self-injurious behavior Affective instability Chronic emptiness Excessive anger Transient dissociation

Family History Bipolar Disorder (n=30) N % 11 36.7 25 83.3 20 66.7 16 53.3 17 56.7 28 93.3 23 76.7 20 66.7 15 50.0

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Note. Fishers exact test of significance is reported in cases where cells had expected counts less than 5. All significance testing was t-tailed.

p .69 .41 .50 .17 .75 1.00 1.00 .02 .93

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53.3 23.3

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43.3 23.3 86.7

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13 7 26

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p .27 .32

36.6 18.1 19.2 14.6

.51 4.0 1.98 .61

.48 .05 .16 .43

58.2 17.4

.26 .64

.61 .45

83 54 192

26.2 18.8 66.9

2.67 .36 4.94

.10 .55 .03

105 52 55 42

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16 7

2 1.23 1.01

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30.0 33.3 30.0 20.0

Family History Negative (n=287) N % 202 70.4 174 60.6

167 50

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9 10 9 6

21 19

70.0 63.3

174 155

60.6 54.0

1.01 .95

.32 .33

19 11

63.3 36.7

192 128

66.9 44.6

.16 .69

.69 .41

13 5

43.3 16.7

159 91

55.4 31.7

1.59 2.91

.21 .09

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Symptom Depressed Mood Loss of interest or pleasure Appetite/Weight Disturbance Decreased Appetite Increased Appetite Decreased Weight Increased Weight Sleep Disturbance Insomnia Hypersomnia Psychomotor Change Psychomotor Agitation Psychomotor Retardation Fatigue Worthlessness/Excessive Guilt Worthlessness Excessive Guilt Concentration/Indecision Diminished Concentration Indecisiveness Death/Suicidal Thoughts Thoughts of Death Suicidal Ideas, Plan, or Attempt

Family History Bipolar Disorder (n=30) N % 24 80.0 21 70.0

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Table 4 Frequency of Current Depressive Symptoms in Psychiatric Outpatients with Borderline Personality Disorder with and without a Family History of Bipolar Disorder

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