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White et al 2003 Family Studies of BPD
1. REVIEW
Family Studies of Borderline Personality
Disorder: A Review
Candace N. White, EdM, John G. Gunderson, MD, Mary C. Zanarini, EdD, and James I. Hudson, MD, ScD
This paper reviews the literature examining the psychopathology found in relatives of individuals
with borderline personality disorder (BPD). Reflecting changes in how BPD has been conceptualized,
researchers have investigated the prevalence of schizophrenia, then mood disorders, and more re-
cently, impulse spectrum disorders in these relatives. This literature does not support a link between
BPD and schizophrenia, is ambiguous about a link between BPD and major depressive disorder, and
suggests a familial aggregation of impulse spectrum disorders and BPD, as well as of BPD itself.
Because of significant methodological problems, most notably indirect assessments and inadequate
sample size, major questions persist about the familial aggregation of this disorder that require
more definitive methods. (HARV REV PSYCHIATRY 2003;11:8–19.)
Since the introduction of borderline personality disorder
(BPD) into the DSM in 1980, our understanding of its eti-
ology has gradually shifted. Attributions initially empha-
sized environmental causes but now lean toward interac-
tion of environmental triggers with an underlying genetic
predisposition. The list of disorders thought to be related to
BPD has also changed over time. Clinicians of the 1970s
and earlier, who had a broad concept of schizophrenia,
concluded that BPD was probably part of a schizophrenia
spectrum.1
Thus early family history studies often used
probands with schizophrenia as comparison groups. Subse-
quently, research and clinical observation led to the concep-
tualization of BPD as an affective spectrum disorder.2
Later
interpretation of BPD as an impulse spectrum disorder3
gave rise to examination of antisocial personality disorder
From McLean Hospital, Belmont, Mass., and the Department of
Psychiatry, Harvard Medical School, Boston, Mass.
Original manuscript received 7 May 2002, accepted for publication
17 June 2002; revised manuscript received 30 July 2002.
Reprint requests: John Gunderson, MD, Psychosocial and Person-
ality Research Program, McLean Hospital, 115 Mill St., Belmont,
MA 02478.
c 2003 President and Fellows of Harvard College
(ASPD) and substance abuse in the relatives of probands
with BPD. During the several decades of reconceptualiza-
tion, multiple family history studies have been completed.
Although such research cannot separate genetic from envi-
ronmental causes, the findings inform both perspectives. In
this review we examine these investigations: their method-
ology, their results, and their implications for understanding
the etiology of BPD.
We searched Medline for articles published in English up
to 1 January 2001 containing the terms “borderline” and
“BPD,” occurring together with “family,” “history,” or “re-
view”. We then examined the reference sections of the re-
sulting papers for additional sources. We found a total of 15
studies assessing the prevalence of psychiatric disorders in
relatives of probands with BPD (see Table 1).
We focus on familial aggregation of disorders that are
thought to be related to BPD. For inclusion, a disorder must
have been included in at least two family history studies, to
allow comparison of the results. The disorders included are
schizophrenia and schizotypal personality disorder (STPD)
in the schizophrenia spectrum; major depressive disorder
(MDD) and bipolar disorder in the affective spectrum; and
substance use disorders and ASPD in the impulsive spec-
trum. For each of these disorders, we will note the preva-
lence or lifetime morbidity risk in relatives of BPD probands
and will comment on any significant differences in such
rates between relatives of BPD probands and comparison
groups.
8
3. 10 White et al.
Harv Rev Psychiatry
January 2003
Within this literature, some authors have calculated mor-
bidity risk (thereby approximating lifetime prevalence by
correcting for the fact that not all relatives will have passed
through the period of risk for development of a disorder),
while others have simply reported prevalence at the time of
the study. Because researchers have used widely differing
methods to estimate the morbidity risk of psychiatric disor-
ders among relatives of probands with BPD, we concluded
that we could not calculate a meaningful combined estimate
using meta-analytic techniques. Rather, we simply report
the estimates, note that they span a certain range, and com-
pare them to those from population-based studies.4−7
Such
estimates can offer a first approximation of the true values
and help in planning future studies in this area.
After we review the results of the 15 investigations in-
volving relatives of BPD probands, we examine methodolog-
ical issues. To do this, we compare the methods used to those
that are proposed as standards for conducting such research.
Because the question of whether BPD is itself familial is so
important, we focus on the nine studies that have consid-
ered this issue. We conclude by highlighting the persistent
questions raised by this literature and identifying topics for
further research.
SCHIZOPHRENIA SPECTRUM DISORDERS
The conceptualization of BPD in the 1970s as a schizophre-
nia spectrum disorder was prompted in part by the broad
concept of schizophrenia in use at that time, by the signif-
icance assigned to patients’ psychosis-like experiences, and
by an adoption study in which persons labeled as having
“borderline schizophrenia” were found to have a disorder
that was genetically linked to schizophrenia.1
Schizophrenia
Four8−11
of the eight studies that assessed schizophrenia
in relatives of BPD probands found no cases among these
individuals. In the remaining four,12−15
the prevalence of
schizophrenia in relatives ranged from 0.7%12
to 4.58%.13
In the reports citing a prevalence of 4.58%13
and 2.6%,14
approximately half of the BPD probands were comorbid
for STPD. This might explain the high risk for schizophre-
nia among relatives in the two studies. Using an earlier
definition of BPD, Soloff and Millward14
subdivided their
BPD sample into “unstable,” “schizotypal,” and “mixed” sub-
groups. The “mixed” subgroup had a significantly higher
prevalence of schizophrenia in relatives than did either of
the other two subgroups. This clarification suggests that
it may be the STPD/BPD comorbidity, not STPD alone,
that correlates with a high prevalence of schizophrenia in
relatives.
Schizotypal Personality Disorder
Soloff and Millward14
found a significantly higher preva-
lence of “eccentric/peculiar” behavior in relatives of
probands with BPD than in relatives of those with depres-
sion or schizophrenia (p = 0.03). This, however, might also
be attributable to their definition of BPD, which included
STPD traits. Only Baron and colleagues9
examined the
prevalence of STPD in relatives of BPD probands and used
STPD probands as a comparison group. In this study rela-
tives of pure STPD probands were significantly more likely
(p < 0.05) to receive a definite or probable STPD diagnosis
(20%) than were relatives of normal controls (9.1%) or rel-
atives of BPD probands (3.1%). Of note, these researchers
found a larger morbidity risk for BPD in relatives of normal
controls than in relatives of STPD probands, and a greater
prevalence of STPD in relatives of normal probands than in
relatives of BPD probands.
In summary, these results do not uphold the hypothesis
that BPD is genetically linked to schizophrenia or STPD.
Thus, there is little support for the concept of BPD as a
schizophrenia spectrum disorder.
AFFECTIVE SPECTRUM DISORDERS
The nature of the relationship between BPD and de-
pression has been the subject of much literature and
controversy.2,16,17
The concept of BPD as an affective spec-
trum disorder arose because of the high frequency of de-
pressive symptoms in patients with BPD and has been but-
tressed by evidence of neurobiological overlap.18
Because
the overlap in phenomenology (i.e., both lability and im-
pulsivity) with bipolar disorder is so evident, the relation-
ship between these two disorders has attracted increasing
interest.19−21
Mood Disorders
In the six studies assessing mood disorders in relatives of
BPD probands,9,11,12,22–24
prevalence ranged from 6.2%22
to
50%.23
Two of the studies12,23
calculated risk for mood dis-
orders in general, without differentiating between bipolar
and unipolar conditions. They found a lifetime prevalence
of 20.7%12
and 50%.23
In studies that differentiated be-
tween unipolar and bipolar disorders, MDD, rather than
bipolar disorder, accounted for most of the mood disorder
prevalence11,15,22
(see Table 1).
Major Depressive Disorder
Ten studies assessed the prevalence or morbidity risk
for MDD in relatives of BPD probands.8–11,13–15,22,24,25
These yielded estimates between 4.6%22
and 31.2%,11
with
4. Harv Rev Psychiatry
Volume 11, Number 1 White et al. 11
particularly low estimates from investigations using chart
reviews.8,22
By comparison, a recent estimate∗
of the lifetime
prevalence of MDD in the general population of the United
States was 17%.26
Two studies14,24
compared the prevalence of MDD in rel-
atives of BPD probands and relatives of MDD probands.
One14
found risk for MDD to be significantly less in relatives
of BPD probands than in relatives of “primary depressive
disorder” probands. The other24
found no significant differ-
ences in relatives’ risk for MDD between the MDD and BPD
proband groups.
Three studies8,13,24
showed that relatives of BPD
probands had a significantly higher prevalence of MDD than
did relatives of persons who had neither disorder. Two of the
studies8,13
found this to be true in comparison to relatives of
schizophrenia probands, and one24
found it to be true in com-
parison to never-psychiatrically-ill controls but not to mood
disorder probands.
To determine whether an elevated prevalence of MDD in
relatives of BPD probands was due to the co-occurrence of
MDD in the BPD probands (since MDD is known to be famil-
ial), three studies11,22,27
compared the prevalence of MDD in
relatives of “pure” BPD probands (i.e., individuals without
comorbid affective disorder) and relatives of BPD probands
with comorbid MDD. In all three investigations, relatives of
the “pure” BPD group had a significantly lower risk for af-
fective disorder than did relatives of the proband group with
co-occurring BPD and MDD. These results have led previous
reviewers15,16
to conclude that BPD and MDD are indepen-
dent disorders that frequently co-occur.
This type of comparison can provide evidence that MDD
in a proband with BPD is associated with a greater proba-
bility that a relative will have MDD. However, it does not
directly address the question of whether BPD and MDD
coaggregate within families (that is, whether the risk of
MDD is elevated in relatives of BPD probands and, con-
versely, whether the risk of BPD is elevated in relatives of
MDD probands—independent of the familial aggregation of
MDD). The most informative determination in this regard
from studies of BPD probands is whether the prevalence of
MDD without BPD is elevated in relatives of BPD probands
who do not have MDD. (See Hudson et al.28,29
for further
discussion of methods to assess familial coaggregation with
∗Although here and elsewhere we provide estimates of the preva-
lence of disorders in the general population, these should be used
only to make very rough comparisons with the prevalences found in
individual studies. Such rates depend on many factors (e.g., demo-
graphics, ascertainment, assessment methods) that may vary from
one investigation to the next. For this reason, within-study compar-
isons between groups would be far more informative.
studies using case-control sampling.) Riso and colleagues,25
for example, found a higher prevalence of MDD in the rel-
atives of BPD probands without mood disorder than in rel-
atives of probands with neither BPD nor MDD. They found
no differences in the prevalence of mood disorders between
relatives of BPD probands without MDD and relatives of
119 probands with mood disorder (including 45 with MDD).
Thus, this investigation provides tentative evidence for co-
aggregation of MDD and BPD in families.
Bipolar Disorder
Seven studies8,10,11,13,15,22,24
calculated a prevalence or mor-
bidity risk for bipolar disorder in relatives of BPD probands.
Results ranged from 0.54%8
to 4.5%10
—figures roughly
equivalent to the 1.6% lifetime prevalence of bipolar disorder
in the general population.26
These rates were no higher than
those found in relatives of comparison group probands. In
the two studies using comparison groups of bipolar disorder
probands,8,22
the rates for bipolar disorder in relatives of the
BPD probands (with or without concurrent mood disorder)
were nonsignificantly lower. In neither study was the rate
of BPD increased in relatives of bipolar disorder probands.
Thus there is no evidence suggesting a familial relationship
between the two disorders.
In summary, these results provide provocative but un-
convincing evidence for a familial relationship of BPD with
MDD, but none for a familial relationship of BPD with bipo-
lar disorder. This disparity, in itself, is confusing. Larger,
better designed studies are needed.
IMPULSE SPECTRUM DISORDERS
The suggestion that BPD represents an impulse spectrum
disorder derives from the many seemingly impulsive behav-
iors that characterize BPD patients, including substance
abuse, violence, self-injurious acts, and disordered eating.3,30
The linkage of ASPD and substance abuse/dependence
as impulse spectrum disorders has been shown both
epidemiologically31
and genetically.32–34
Substance Use Disorders
Eleven studies9–15,22–24,35
calculated the lifetime prevalence
or morbidity risk for alcohol abuse or dependence in relatives
of BPD probands. Estimates for risk in relatives ranged from
7.4%12
to 25.9%.24
The studies differed in their comparisons,
however: some required alcohol “dependence,” whereas oth-
ers included persons with a diagnosis of alcohol abuse. No-
tably, the inclusion of only “severe alcoholics” may account
for the low prevalence found by Stone and colleagues.12
Nev-
ertheless, this range appears to be somewhat higher than
5. 12 White et al.
Harv Rev Psychiatry
January 2003
the 14.1% lifetime prevalence of alcohol dependence26
—
but nearly twice the 9.4% lifetime prevalence of alcohol
abuse26
—seen in the general population. The difference is
greater when the estimate is contrasted with the lifetime
prevalence rates for females, who comprise the majority
of most BPD samples—i.e., abuse, 6.4%; and dependence,
8.2%.26
The prevalence of alcohol abuse was nonsignificantly
higher in relatives of BPD probands than in those of normal
controls.9,12,24
Two studies13,23
found prevalence of alcohol
abuse or dependence to be significantly higher in relatives of
BPD probands than in relatives of schizophrenia probands.
However, no researchers separated BPD probands with and
without alcohol use disorders for such examination. Thus,
it is unclear to what extent the elevated prevalence of alco-
hol abuse or dependence in relatives of BPD probands may
be due to the well-documented familial aggregation of al-
cohol abuse or dependence. Furthermore, no studies have
looked at the prevalence of BPD in probands with alcohol
abuse/dependence.
Six studies calculated a prevalence of drug abuse or
dependence in relatives of BPD probands; their estimates
ranged from 0.8%22
to 20.4%.24
Lifetime prevalence in the
general population is 4.4% for abuse and 7.5% for depen-
dence (3.5% and 5.9%, respectively, for females).26
Although
trends were detected toward more abuse in relatives of BPD
probands than in relatives of comparison probands,13,15,24
the differences were not significant.
Antisocial Personality Disorder
Seven studies10,11,13–15,22,23
assessed the familial aggregation
of ASPD in the relatives of BPD and comparison probands.
The prevalence/morbidity risk in relatives ranged from 0%13
to 13.6%.11
The highest prevalences were found in stud-
ies that relied on semistructured interviews of probands
or relatives.10,11,13
The median prevalence of 7% is twice
that seen in the general population (3.5%26
). Of the five
studies that compared the prevalence of ASPD in rela-
tives of BPD probands to the prevalence in relatives of
other probands,11,13–15,23
only Schulz and colleagues13
found
a significant difference. ASPD was significantly more com-
mon among the relatives of borderline probands without
ASPD than comparison probands—in this case, schizophre-
nia probands without ASPD. Taken together, these results
suggest familial aggregation of BPD and ASPD.
It is notable that the case for BPD as an impulse spec-
trum disorder (i.e., related to substance use disorders and to
ASPD) rests largely on studies in which BPD probands were
compared to schizophrenia probands. It is possible that rel-
atives of individuals with schizophrenia have an unusually
low risk for impulsive spectrum disorders. Nonetheless, the
prevalences of ASPD and substance use disorders in rela-
tives of persons with BPD seem to be markedly increased.
Thus, the existing evidence offers clear evidence in sup-
port of a relationship between BPD and impulse spectrum
disorders.
BORDERLINE PERSONALITY DISORDER
Nine studies8–12,22,24,36,37
examined the occurrence of border-
line psychopathology (by various definitions) in relatives of
BPD probands. Four of them8−11
reported lifetime morbidity
risk for BPD in relatives; five12,22,24,36,37
calculated only the
unadjusted lifetime prevalence. The prevalence or morbidity
risk for BPD in relatives ranged from 0.8%22
to 24.9%.11
Epi-
demiological studies4−7
indicate a 0.6–3% prevalence of BPD
in the general population. Hence, the range reported here
demonstrates a 4- to 20-fold increase of BPD in relatives of
BPD probands compared to the general population. As noted
in the methodological review of these nine studies (see be-
low), the studies reporting the highest risk in relatives9,11
assessed the relatives indirectly.
Six of the nine studies examined the prevalence or mor-
bidity risk for BPD in relatives of BPD probands and in those
of comparison groups. Four8,9,11,37
of the six found a signifi-
cantly higher prevalence or morbidity risk for BPD in the
relatives of the BPD probands. The fifth36
found a trend
(p = 0.07), but this result was derived from only 12 BPD
probands. The only investigation that did not find a higher
prevalence of BPD among relatives of BPD probands12
was
conducted prior to the establishment of DSM criteria for
BPD.
Three studies22,24,37
examined the prevalence of Cluster
B disorders (which includes histrionic, antisocial, and nar-
cissistic personality disorders, as well as BPD) in relatives of
BPD probands. All three had small numbers of probands and
expanded to include other Cluster B disorders to enhance the
power to detect coaggregation, at the cost of losing specificity
for BPD. Johnson and colleagues37
and Riso and coworkers,24
using structured interviews for assessment of relatives, cal-
culated a prevalence in relatives of 21% and 22.2%, respec-
tively. The latter authors found a significantly higher risk
for Cluster B disorders in relatives of BPD probands than in
relatives of never-psychiatrically-ill controls; they found a
similarly high prevalence of Cluster B disorders in the rela-
tives of probands with mood disorders. Pope and colleagues22
(using less rigorous methods than those employed in the
other two studies) found a low prevalence (7.7%) of Cluster
B disorders among relatives of probands with BPD. Nonethe-
less, the figure was still significantly higher than those es-
timated for the relatives of schizophrenia and bipolar disor-
der probands. The high prevalence of Cluster B personality
6. Harv Rev Psychiatry
Volume 11, Number 1 White et al. 13
disorders observed in this review in relatives of BPD
probands suggests that certain traits within this cluster,
such as affective instability or impulsivity, may aggregate
with BPD in families (see Discussion, below).
To examine the evidence for the familial aggregation of
BPD, we calculated ratio of the risk of BPD in relatives of
probands with BPD versus the risk in relatives of probands
without BPD. For this analysis, we included all studies that
made BPD diagnoses of probands using DSM criteria by ei-
ther chart review or structured interview, assessed BPD (or
Cluster B disorders) in relatives, and employed a compari-
son group. For the estimate of risk, we used either the crude
lifetime prevalence or the estimated morbidity risk. If both
measures could be calculated, we chose the morbidity risk
because it represents a more accurate assessment of true
risk. The six studies shown in Table 28,9,11,22,24,37
met these
inclusion criteria for risk-ratio analysis.
To judge from these studies, BPD is consistently more
common among the relatives of BPD probands than among
the relatives of non-BPD probands. However, the differences
in diagnostic criteria for BPD, in the diagnoses of comparison
groups, in recruitment procedures, and in interview methods
of these studies may have substantially altered the “true”
estimate of risk. Certainly this heterogeneity precludes a
solid estimation of risk ratio using meta-analytic techniques.
METHODOLOGICAL ISSUES
In reviewing the methodological issues of the nine studies of
BPD’s familial aggregation,8−12,22,24,36,37
we follow the stan-
dards for family risk studies established by Knowles and
colleagues38
and used by Dahl27
in 1994 on a portion of this
literature. The methodological quality of the family studies
is assessed on the following variables: sample size, proband
demographic representativeness, and subject selection; di-
agnostic criteria and assessment means (e.g., structured in-
terview, questionnaire), and percentage of relatives directly
interviewed (see Table 3).
Sample Size
In the nine studies reviewed here, the number of BPD
probands ranged from 11 to 83, and the number of relatives
assessed ranged from 31 to 249. Generally, the number of rel-
atives assessed was proportional to the number of probands;
a mean of 3.35 relatives was assessed for each proband. All
but one of these studies employed indirect methods to as-
sess at least some of the relatives. The exception was Reich
and colleagues’ investigation,36
which assessed all available
relatives (60%) by asking them to complete a questionnaire.
Because the sample sizes used in these studies were small,
the confidence intervals for the estimates of effects are wide.
This limits the conclusions that can be drawn, in two impor-
tant ways. First, a wide range of prevalences for a given dis-
order among relatives of probands with BPD is consistent
with the data; that is, the data cannot distinguish whether
the “true” level of familiality is very large or very small.
Second, it is difficult to compare the risks of disorders in the
relatives of BPD probands with the risks in relatives of non-
BPD probands. For example, suppose that the lifetime risk
for BPD among relatives of probands with BPD is 10%. To
have 90% power to show that this risk is significantly greater
than a 4% risk of BPD among relatives of another proband
group would require a sample of over 400 relatives per group.
None of the studies approach this sample size. Thus, all stud-
ies are seriously underpowered, creating a high likelihood of
a type-II error (i.e., not detecting true differences between
groups).
Representativeness
Five of the nine studies shown in Table 3 included both males
and females, over a wide age range, in their proband sam-
ples. Loranger and colleagues8
had only females in their
BPD proband sample, and Johnson and coworkers37
in-
cluded only adolescents. Because the relatives included both
males and females over a wide age range, it is possible in
principle to examine effects of age and gender. Although
most studies adjusted for age in their estimates of preva-
lence in relatives, none examined the effects of gender.
Subject Selection
For all studies, case-control sampling was used; that is, sub-
jects were selected for the presence or absence of certain
conditions. The ascertainment for all studies except one9
in-
volved selecting patients with BPD from either inpatient
or outpatient settings. None attempted to locate individu-
als with BPD who were not seeking treatment or a random
sample of persons with BPD from the general population.
The remaining study9
recruited college students and hospi-
tal staff, producing a small group of BPD probands (n = 17)
and a much larger group of normal controls (n = 90).
Diagnostic Assessments
The ideal family study would employ standardized diagnos-
tic criteria and would confirm the diagnosis using a second
method. Not surprisingly, the earliest family studies gen-
erally had the weakest diagnostic methodology. Stone and
colleagues,12
for example, did not employ standardized diag-
nostic criteria for BPD. The subsequent family studies have
all used DSM-based diagnostic criteria but have varied as to
which DSM system and which assessment instrument they
utilized. Loranger and colleagues8
selected probands using
7. 14 White et al.
Harv Rev Psychiatry
January 2003
TABLE 2. Family Studies of BPD Meeting Criteria for Assessment of Risk Ratios
Relatives
Probands
At riska
BPD Morbidity Risk ratio
Study Diagnostic method Group type n n (n) casesb
risk (%)c
(95% CI)
Loranger et al.8 DSM-III criteria Inpatients
retrospectively applied BPD 83 338 249 29 11.65
to charts Schizophrenia 100 482 353.5 5 1.41 8.2 (3.2, 21)
Bipolar disorder 100 537 413.5 3 0.73 16 (4.9, 52)
Pope et al.22,d DSM-III criteria Inpatients
retrospectively applied BPD 33 130 10 7.7
to charts Schizophrenia 39 181 4 2.2 3.5 (1.1, 11)
Bipolar disorder 34 173 1 0.6 13 (1.7, 103)
Baron et al.9,e SIB College students, hospital staff
BPD 17 60 39 7 17.9
“Pure STPD” 36 56 36 2 5.6 3.2 (.72, 15)
Normal 90 376 344 14 4.1 4.4 (1.9, 10)
Zanarini et al.11 DIB, DIPD Outpatients
BPD 48 240 177 44 24.9
ASPD 29 139 97.5 4 4.1 6.1 (2.2, 16)
DTPD, “dysthymic other PD” 26 109 83.3 8 9.6 2.6 (1.2, 5.3)
Johnson et al.37 SCID-II Inpatients
BPD ? 39 4 10.3
AVPD ? 62 2 3.2 3.2 (.61, 17)
No PD 17 46 0 0
Riso et al.24,f PDE Outpatients
BPD 11 54 12 22.2
Mood disorder 119 563 121 21.2 0.96 (0.5, 1.9)h
Normal 45 229 16 7.0 3.6 (1.6, 8.2)i
AVPD, avoidant personality disorder; ASPD, antisocial personality disorder; BPD, borderline personality disorder; CI, confidence interval;
DIB, Diagnostic Interview for Borderlines; DIPD, Diagnostic Interview for Personality Disorders; DTPD, dysthymic personality disorder;
PD, personality disorder; PDE, Personality Disorder Examination; SCID-II, Structured Clinical Interview for DSM-III-R; SIB, Schedule for
Interviewing Borderlines; STPD, schizotypal personality disorder.
aDetermined by the method used to calculate morbidity risk. Pope et al. and Johnson et al. did not calculate morbidity risk and therefore
did not report the number of relatives “at risk” for BPD.
bLoranger et al. included as “cases” only those relatives who had been treated for a mental disorder.
cValues were age-corrected by the Str¨omgren method in the studies by Loranger et al. and Baron et al. and by the Weinberg short method
in the study by Zanarini et al.; they were not corrected in the remaining investigations.
dPope et al. assessed the dramatic cluster of personality disorder (i.e., histrionic personality disorder, BPD, and ASPD) rather than BPD
alone.
eBaron et al. corrected for use of the family history method.
fRiso et al. included only probands with BPD and no mood disorder; they assessed Cluster B rather than BPD alone in relatives.
gRisk ratio adjusted for gender, birth cohort, interview status, and proband comorbidity; unadjusted risk ratio is 1.0 (0.61, 1.8).
hRisk ratio adjusted for gender, birth cohort, interview status, and proband comorbidity; unadjusted risk ratio is 3.2 (1.6, 6.3).
DSM-II (i.e., criteria for personality disorder not otherwise
specified, rather than specifically for BPD). As noted earlier,
Loranger and colleagues8
and Pope and coworkers22
used
chart review to assess both probands and relatives. In Baron
and colleagues’ sample,9
15 of the 17 BPD probands had
“probable” BPD. Reich36
measured Axis II in probands and
relatives with the Personality Diagnostic Questionnaire, an
instrument likely to produce false positives. (Of note, de-
spite the high sensitivity of this questionnaire, it identi-
fied no relatives with BPD from the normal control group.)
Although five studies9−11,24,37
used DSM-based structured
interviews to establish the proband diagnoses, DSM crite-
ria have changed over the years, and only Zanarini and
colleagues11
confirmed the diagnosis using a second method.
Axis I assessment has also progressed over time, from
unstructured methods,8,12,22
to the Schedule for Affective
9. 16 White et al.
Harv Rev Psychiatry
January 2003
Disorders and Schizophrenia,9,10
to the Structured Clinical
Interview for the DSM,11,24,36,37
an instrument that assesses
all Axis I diagnoses.
Rater Reliability and Blindness
As shown in Table 3, there is an obvious progression in
the assessment of relatives. Stone’s pioneering study12
em-
ployed multiple methods to assess relatives; these meth-
ods (some blind, some not) were without established reli-
ability. (It is also worth noting that the family members
included in Stone’s study, unlike those in the other stud-
ies reviewed here, were not limited to first-degree rela-
tives.) In six8,11,22,24,36,37
of the eight subsequent studies re-
viewed, assessments of relatives were blind to the proband’s
diagnosis. Interrater reliability was recorded in only four
studies.8,9,25,37
Direct versus Indirect Assessment
Although family history (relying primarily on the proband’s
report) and family study (relying primarily on direct in-
terviews of relatives) usually produce similar results, di-
rect interviews remain the standard for establishing valid
diagnostic assessments. The ideal study would blindly as-
sess all relatives directly; direct interviews usually de-
tect less severe cases of the disorder in question40−42
and
avoid unidentifiable reporting biases,43
resulting in a higher
prevalence.25,44−46
In four10,12,24,37
of the nine studies in-
cluded here, the researchers directly interviewed a frac-
tion of the relatives (more than 50% in two cases12,37
). In
Baron and colleagues’ investigation,9
70% of the relatives
of normal control probands but none of the relatives of BPD
and STPD probands received direct interviews. Johnson and
coworkers37
and Riso and colleagues24
reported no differ-
ence between BPD and comparison groups in the propor-
tion of relatives who were directly interviewed. Stone and
coworkers12
did not mention whether there was a signifi-
cant difference among their groups in number of relatives
directly interviewed. No studies indicated whether relatives
refused participation or how many declined to have direct
interviews.
The two studies that found the highest risk for BPD in
relatives (24.9%11
and 17.9%9
) relied solely on indirect in-
terviews when obtaining information on relatives of BPD
probands. Moreover, Links and colleagues10
reported a BPD
prevalence of 3.4% when relatives were interviewed directly
but 15.1% when indirect methods were employed. To com-
pensate for the expectation of false negatives from indirect
assessments, the authors lowered the threshold for achiev-
ing a BPD diagnosis when indirect methods were used: rela-
tives who were indirectly assessed were required to demon-
strate only three of the seven criteria for BPD, while those
directly interviewed had to meet all seven. Of note, Baron
and coworkers9
adopted a similar compensatory strategy and
found significant differences in prevalence of BPD in rela-
tives only after making this correction. These results suggest
that the reported risk for BPD in relatives may increase
with the use of indirect methods. Although this discrep-
ancy is unusual, Andreasen and colleagues40
have previ-
ously reported a similar situation with other psychiatric con-
ditions (ASPD and psychotic disorders), presumably due to
the relatives’ underreporting. This explanation might also
hold true for BPD—i.e., relatives with BPD might under-
report their symptoms when directly interviewed, possibly
because of denial or fear of stigma, thereby causing false
negatives. Conversely, when indirect methods are used, BPD
probands might exaggerate BPD features among their rela-
tives, thereby causing false positives. The latter explanation
is consistent with the tendency of persons with BPD to de-
value or vilify members of their family.47
An implication of
this review is that future family studies should incorporate
both direct and indirect methods, as Links and colleagues10
did, comparing the frequencies of BPD determined with each
method and exploring reasons for the differences.44
Comparison Groups
Proper selection of comparison groups is an essential feature
of family studies using case-control sampling. The ideal fam-
ily study would have at least one comparison group of indi-
viduals who are representative of those at risk for the BPD
and are derived from the same population source (e.g., hos-
pital, community) that gave rise to BPD cases, but do not
have BPD. The comparison group(s) and the BPD probands
should have the same distribution of any variables that could
influence risk of BPD, including all forms of psychopathol-
ogy (see Wacholder et al.48
). Only three studies,9,24,36
all of
which used “normals” as a comparison group, came close to
fulfilling such requirements.
Comparison groups of probands with psychiatric disor-
ders other than BPD, the strategy used in most of the stud-
ies reviewed here, are also useful, primarily to examine
patterns of coaggregation of BPD with other disorders in
families. They are less useful in assessing the family aggre-
gation of BPD itself, because it is possible that relatives of
probands with a condition other than BPD, such as a mood
disorder, may have an elevated prevalence of BPD compared
to relatives of probands with neither BPD nor mood disorder.
The ideal family study would include comparison groups
that could reflect a suspected relationship due to comorbid-
ity (or other overlap in psychopathology). In this regard,
the comparison groups selected for BPD family risk studies
have changed over the years. As noted, most of the earlier
10. Harv Rev Psychiatry
Volume 11, Number 1 White et al. 17
studies compared BPD probands to probands with Axis I
disorders—i.e. schizophrenia or mood disorders. No stud-
ies, however, have included comparison groups consisting of
probands with substance abuse or eating disorders, which
are suspected to be familial. Two studies have used person-
ality disorder comparison groups—i.e., avoidant personality
disorder37
and ASPD.11
Of these, only the latter can be said
to be a truly near-neighbor comparison group.
Comparability of basic demographic features that might
influence prevalence of disorders can be achieved either by
matching or by statistical control. In only two9,24
of the ten
studies reviewed were comparison group probands matched
by age, sex, and race; in another four,8,11,12,37
demographic
similarities and differences were identified, but whether
groups matched was not reported.
DISCUSSION
A significant amount of research has been published on the
familiality of BPD and its coaggregation with other disor-
ders. As noted above, these studies have generally supported
the idea that BPD “breeds true.” However, major problems
exist in the quality of the methodology employed in these
investigations. The fact that no adequately sized study us-
ing direct assessments of relatives has been conducted for
BPD contrasts dramatically with the fact that by 1995, this
method had been utilized in ten studies of mood disorders,
eight of anxiety disorders, nine of schizophrenia, and five of
alcohol abuse/dependence.49
In the absence of such an in-
vestigation for BPD, Dahl’s conclusion27
in 1994 that BPD’s
familiality had not been convincingly established unfortu-
nately still holds true. The need for such research is un-
derscored by Torgersen and colleagues’ recent twin study,50
which suggested a surprisingly strong heritability (0.52–
0.69) for BPD. That report draws attention to the need for
research examining both genetic and environmental under-
pinnings of the disorder. Family studies, done well, could
help to clarify which traits are transmitted.
The existing studies investigating BPD’s coaggregation
with schizophrenia and bipolar disorder have been negative.
Those that looked at depressive or impulse spectrum disor-
ders yielded results that are promising but still ambiguous.
Studies with more rigorous methodology are needed to con-
firm such linkages. Results obtained so far point toward the
use of an alternative strategy—i.e., following Silverman and
colleagues’ approach15
and examining the familial aggrega-
tion of BPD component traits, such as affective instability
and impulsivity, from a dimensional perspective. In this in-
vestigation, the familial aggregation was stronger for im-
pulsivity and affective instability than for BPD. Moreover,
these traits appeared to aggregate separately, with both be-
ing necessary for a diagnosis of BPD. Similarly, Livesley and
colleagues51
have proposed that emotional dysregulation is
the core aspect of the BPD construct; in their genetic fac-
tor analysis, this dimension seemed to account for much of
the genetic variance. Such investigations suggest that the
component traits of BPD may be inherited independently.
A clear implication of this review is that a future fam-
ily study should examine whether affective and impulsive
traits, as well as other BPD characteristics such as aggres-
sivity and unstable interpersonal relationships, aggregate
individually or coaggregate with other traits in families.
As noted, the evidence for increased Cluster B disorders in
families of BPD probands also supports the value of such
a study. We would hypothesize that individuals with BPD
share the histrionic personality disorder trait of affective in-
stability; those with ASPD share BPD traits of impulsivity
and aggressivity; and those with narcissistic personality dis-
order share the BPD trait of interpersonal instability. Such
a model predicts that persons with any of these personality
disorders are likely to have relatives with similar traits, but
that to develop BPD requires a combination of several such
traits.
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