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Comprehensive Psychiatry 55 (2014) 1491 1497
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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
Department of Psychiatry and Human Behavior, Brown Medical School, Providence, RI, USA

Abstract

Diagnostic confusion sometimes exists between bipolar disorder and borderline personality disorder (BPD). To improve the recognition
of bipolar disorder researchers have identified nondiagnostic factors that point toward 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 Diagnostic Assessment and Services
(MIDAS) project, we compared the demographic, clinical, 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 interviews. Three hundred
seventeen patients without bipolar disorder were diagnosed with DSM-IV borderline personality disorder. Slightly less than 10% of the 317
patients with BPD (9.5%, n = 30) reported a family history of bipolar disorder in their first-degree relatives. There were no 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 was no difference in the frequency of other criteria for BPD such as affective instability,
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.
2014 Elsevier Inc. All rights reserved.

1. Introduction include the underprescription of mood stabilizing medica-

The goal of the present investigation is to determine
whether patients with borderline personality disorder (BPD)
with a first-degree relative with bipolar disorder differ from
BPD 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.
The underrecognition and underdiagnosis of bipolar
disorder is a significant clinical problem [14]. 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 implications of
underdiagnosing bipolar disorder in depressed patients
Corresponding author at: 146 West River Street, Providence, RI
02904, USA.
E-mail address: mzimmerman@lifespan.org (M. Zimmerman).
http://dx.doi.org/10.1016/j.comppsych.2014.05.012
0010-440X/ 2014 Elsevier Inc. All rights reserved.
tions, an increased risk of rapid cycling, and increased costs
of care [2,6,7]. Experts have called for improved recognition
of bipolar disorder because of these individual and public
health consequences [1,3].
The relationship between bipolar disorder and BPD has
been the subject of some controversy. The relatively high
frequency of diagnostic co-occurrence and resemblance of
some 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 [1013].
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
1492 M. Zimmerman et al. / Comprehensive Psychiatry 55 (2014) 14911497
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 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 disorder, approximately 10% of the
patients with bipolar I disorder and 16% of patients with
bipolar II disorder were diagnosed with BPD.
To improve the recognition of bipolar disorder re-
searchers have identified nondiagnostic factors that point
toward bipolar disorder. One such factor is the presence of a
family history of 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] considered individuals with a
family history of bipolar disorder to have a variant of the
disorder (bipolar type 5), and Ghaemi et al. [16] list a
positive family history of bipolar disorder as one of their
criteria for bipolar spectrum disorder.
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 found
an elevated rate of bipolar disorder in first-degree relatives [19
23], this does not preclude 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 person-
ality disorder who did and did not have a family history of
bipolar disorder.
2. Methods
The Rhode Island MIDAS project represents an integra-
tion 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
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 training clinic that predominantly serves
lower income, uninsured, and medical assistance patients.
Data on referral source were recorded for the last 1800
patients enrolled in the study. Patients were most frequently
referred from primary care physicians (29.6%), psychother-
apists (16.6%), and family members or friends (18.4%). The
Rhode Island Hospital institutional review committee
approved the research protocol, and all patients provided
informed, written consent.
The sample examined in the present report was derived from
the 3600 psychiatric 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 DSM-IV (SCID) [25] supplemented with
items from the Schedule for Affective Disorders and
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 been modified at times. The assessment of all DSM-IV
personality disorders was not introduced 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, 3465 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 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%,
n = 148); the remainder were married (23.0%, n = 73),
divorced (13.9%, n = 44), separated (4.4%, 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 minority graduated a 4-year college (16.7%, n = 53).
The racial composition of the sample was 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.
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 Childhood Trauma Questionnaire
emotional abuse, physical abuse, sexual abuse, physical
neglect and emotional neglect.
From the SADS we examined the items assessing psychic
and somatic anxiety, anger and irritability, and somatization.
The SADS ratings referred to symptom severity during the past
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 hospitalizations and suicide attempts.
 M. Zimmerman et al. / Comprehensive Psychiatry 55 (2014) 14911497 1493

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.
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 college degrees in the social or biological
sciences. Research assistants received 3 to 4 months of
training during which they observed at least 20 interviews,
and they were observed and supervised in their administra-
tion of more than 20 evaluations. Psychologists only
observed 5 interviews, and they were observed and
supervised in their administration of 15 to 20 evaluations.
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 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 exact, or near exact,
agreement with a senior diagnostician on five consecutive
evaluations. Throughout the MIDAS project, ongoing
supervision of the raters consisted of weekly diagnostic
case conferences involving all members of the team. In
addition, every case was reviewed by the senior author.
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 ( = 0.90, n = 23), dysthymic disorder ( = 0.88,
n = 5), bipolar disorder ( = 0.75, n = 8), panic disorder ( =
0.95, n = 12), social phobia ( = 0.84, n = 19), obsessive
compulsive disorder ( = 1.0, n = 6), specific phobia ( =
0.93, n = 9), generalized anxiety disorder ( = 0.85, n = 14),
posttraumatic stress disorder ( = 0.87, n = 10), alcohol abuse/
dependence ( = 0.64, n = 8), drug abuse/dependence ( =
0.64, n = 6), and any somatoform disorder ( = 1.0, n = 5).
The reliability for diagnosing BPD ( = 1.0) was excellent. The
reliabilities of any PD ( = 0.90) any Cluster A ( = 0.79), B
( = 0.79), or C PD ( = 0.93) were good to excellent. Too few
patients were diagnosed with other individual PDs to calculate
kappa coefficients. However, intraclass correlation coefficients
(ICC) of criterion count dimensional scores were high (paranoid,
ICC = 0.92; schizoid, ICC = 0.95; schizotypal, ICC = 0.82;
antisocial, ICC = 0.95; borderline, ICC = 0.95; histrionic,
ICC = 0.91; narcissistic, ICC = 0.91; avoidant, ICC = 0.96;
dependent, ICC = 0.97; obsessivecompulsive, ICC = 0.90).
2.1. Statistical analysis
We compared the demographic and clinical characteris-
tics of patients with DSM-IV BPD 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-square
statistic, or by Fisher's exact test if the expected value in any
cell of a 2 2 table was less than 5.
3. Results
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

Table 1
Demographic characteristics in psychiatric outpatients with borderline personality disorder with and without a family history of bipolar disorder.
Family history bipolar Family history negative
disorder (n = 30) (n = 287)
N % N % 2 P
Gender
Male 3 10.0 86 30.0 5.36 .02
Female 27 90.0 201 70.0
Education
Less than high school 4 13.3 28 9.8 3.09 .21
Graduated high school 18 60.0 214 74.6
Graduated college 8 26.7 45 15.7
Marital status
Married 9 30.0 64 22.3 9.19 .10
Living with someone 5 16.7 31 10.8
Widowed 1 3.3 1 0.3
Separated 1 3.3 13 4.5
Divorced 6 20.0 38 13.2
Never married 8 26.7 140 48.8

Mean SD Mean SD t P
Age 35.8 13.5 31.8 10.0 1.59 .12
1494 M. Zimmerman et al. / Comprehensive Psychiatry 55 (2014) 14911497

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
affective instability, impulsivity, or suicidal behavior. The
patients with a positive family history were significantly less
likely to report excessive or inappropriate anger.
The patients with a positive family history reported a
significantly higher rate of increased 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
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 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 SADS. There was no difference on any of the 5 subscales
of the childhood trauma questionnaire.
4. Discussion
A family history of bipolar disorder has been considered
an indicator of bipolar spectrum disorder among patients
who themselves do not report a history of manic or
hypomanic episodes [15,16]. Some experts consider BPD
to be part of the bipolar spectrum, though reviews of the
BPDbipolar link have reached contrasting conclusions
[1013]. In the present study we examined whether a family
history of bipolar disorder among patients with BPD would

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.
Disorder Family history bipolar Family history negative 2 P
disorder (n = 30) (n = 287)
N % N %
Mood disorders
Major depressive disorder 19 63.3 187 65.2 .04 .84
Dysthymic disorder 3 10.0 37 12.9 .21 1.00
Any depressive disorder 20 66.7 198 69.0 .07 .79
Anxiety disorders
Panic w/or w/out agoraphobia 11 36.7 75 26.1 1.53 .22
Specific phobia 11 36.7 65 22.6 2.93 .09
Social phobia 14 46.7 137 47.7 .01 .91
Posttraumatic stress disorder 8 26.7 75 26.1 .00 .95
Obsessivecompulsive disorder 5 16.7 34 11.8 .59 .39
Generalized anxiety disorder 10 33.3 89 31.0 .07 .79
Any anxiety disorder 27 90.0 241 84.0 .76 .60
Substance use disorders
Alcohol abuse/dependence 4 13.3 55 19.2 .61 .44
Drug abuse/dependence 1 3.3 39 13.6 2.59 .11
Any substance use disorder 5 16.7 77 26.8 1.46 .23
Any eating disorder 5 16.4 41 14.3 .12 .78
Any somatoform disorder 6 20.0 43 15.0 .52 .43
Any impulse control disorder 1 3.3 7 2.4 .09 .55
Three or more Axis I disorders 19 63.3 191 66.6 .13 .72
Personality disorders a
Paranoid 2 11.1 26 16.8 .38 .74
Schizoid 0 0.0 2 1.3 .24 1.00
Schizotypal 0 0.0 3 1.9 .36 1.00
Antisocial 0 0.0 12 7.7 1.50 .62
Histrionic 0 0.0 5 3.2 .60 1.00
Narcissistic 0 0.0 9 5.8 1.10 .60
Avoidant 4 22.2 38 24.5 .05 1.00
Dependent 2 11.1 14 9.0 .08 .68
Obsessivecompulsive 3 16.7 15 9.7 .85 .36
Any personality disorder 8 44.4 82 52.9 .46 .50
Two or more personality disorders 3 16.7 29 18.7 .05 1.00
a
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.
 M. Zimmerman et al. / Comprehensive Psychiatry 55 (2014) 14911497 1495

Table 3
Borderline personality disorder criteria in psychiatric outpatients with borderline personality disorder with and without a family history of bipolar disorder.
Criterion Family history bipolar Family history negative 2 p
disorder (n = 30) (n = 287)
N % N %
Abandonment fear 11 36.7 95 33.1 .16 .69
Interpersonal instability 25 83.3 220 76.7 .69 .41
Identity disturbance 20 66.7 208 72.5 .45 .50
Impulsive behavior 16 53.3 189 65.9 1.86 .17
Suicidal/self-injurious behavior 17 56.7 154 53.7 .10 .75
Affective instability 28 93.3 267 93.0 .00 1.00
Chronic emptiness 23 76.7 220 76.7 .00 1.00
Excessive anger 20 66.7 245 85.4 6.93 .02
Transient dissociation 15 50.0 146 50.9 .01 .93
Fisher's exact test of significance is reported in cases where cells had expected counts less than 5. All significance testing was t-tailed.

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 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 that we found that supported the bipolar
spectrum hypothesis was a higher rate of increased appetite
in the patients with a positive family history. Other
researchers have found that reverse vegetative symptoms
are more frequent in patients with bipolar disorder [3234].
Overall, then, our results suggest that a positive family
history of bipolar disorder in patients with BPD should not
be 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

Table 4
Frequency of current depressive symptoms in psychiatric outpatients with borderline personality disorder with and without a family history of bipolar disorder.
Symptom Family history bipolar Family history negative 2 p
disorder (n = 30) (n = 287)
N % N %
Depressed mood 24 80.0 202 70.4 1.23 .27
Loss of interest or pleasure 21 70.0 174 60.6 1.01 .32
Appetite/Weight disturbance
Decreased appetite 9 30.0 105 36.6 .51 .48
Increased appetite 10 33.3 52 18.1 4.0 .05
Decreased weight 9 30.0 55 19.2 1.98 .16
Increased weight 6 20.0 42 14.6 .61 .43
Sleep disturbance
Insomnia 16 53.3 167 58.2 .26 .61
Hypersomnia 7 23.3 50 17.4 .64 .45
Psychomotor change
Psychomotor agitation 13 43.3 83 26.2 2.67 .10
Psychomotor retardation 7 23.3 54 18.8 .36 .55
Fatigue 26 86.7 192 66.9 4.94 .03
Worthlessness/Excessive guilt
Worthlessness 21 70.0 174 60.6 1.01 .32
Excessive guilt 19 63.3 155 54.0 .95 .33
Concentration/Indecision
Diminished concentration 19 63.3 192 66.9 .16 .69
Indecisiveness 11 36.7 128 44.6 .69 .41
Death/Suicidal thoughts
Thoughts of death 13 43.3 159 55.4 1.59 .21
Suicidal ideas, plan, or attempt 5 16.7 91 31.7 2.91 .09
1496 M. Zimmerman et al. / Comprehensive Psychiatry 55 (2014) 14911497
history of bipolar disorder in patients with borderline
personality disorder is not sufficient to warrant treatment
with mood stabilizer medication.
The limitations of the study should be considered. The
sample of patients with a positive 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. However,
there was no evidence that nonsignificant trends were in the
direction supporting the 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 bio-
markers 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.
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 interviews of family members, other reports
from our group have shown that this method of ascertaining
information was useful as a diagnostic validator [37,38].
Moreover, clinicians typically use the family history
approach toward eliciting information about a family history
of psychopathology, thus these results are more relevant to
usual clinical practice.
Finally, the study was conducted in a single site in which
the majority of patients were white, were high school
graduates, and had health insurance. However, it is not clear
why a family history of bipolar disorder would be a less valid
indicator of the bipolar spectrum in our sample than in
samples with different demographic characteristics.
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