REVIEW

Family Studies of Borderline PersonalityDisorder: 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 individualswith 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 betweenBPD and schizophrenia, is ambiguous about a link between BPD and major depressive disorder, andsuggests 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 inadequatesample size, major questions persist about the familial aggregation of this disorder that requiremore 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 geneticpredisposition. The list of disorders thought to be related toBPD has also changed over time. Clinicians of the 1970sand earlier, who had a broad concept of schizophrenia,concluded that BPD was probably part of a schizophreniaspectrum.1 Thus early family history studies often usedprobands with schizophrenia as comparison groups. Subse-quently, research and clinical observation led to the concep-tualization of BPD as an affective spectrum disorder.2 Laterinterpretation of BPD as an impulse spectrum disorder3

gave rise to examination of antisocial personality disorder

From McLean Hospital, Belmont, Mass., and the Department ofPsychiatry, Harvard Medical School, Boston, Mass.

Original manuscript received 7 May 2002, accepted for publication17 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 probandswith 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. Inthis review we examine these investigations: their method-ology, their results, and their implications for understandingthe etiology of BPD.

We searched Medline for articles published in English upto 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 15studies assessing the prevalence of psychiatric disorders inrelatives of probands with BPD (see Table 1).

We focus on familial aggregation of disorders that arethought to be related to BPD. For inclusion, a disorder musthave been included in at least two family history studies, toallow comparison of the results. The disorders included areschizophrenia and schizotypal personality disorder (STPD)in the schizophrenia spectrum; major depressive disorder(MDD) and bipolar disorder in the affective spectrum; andsubstance 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 probandsand will comment on any significant differences in suchrates between relatives of BPD probands and comparisongroups.

8

TA

BL

E1.

Ris

kof

Psyc

hiat

ric

Dis

orde

rsin

Rel

ativ

esof

BPD

Prob

ands

Ris

k(%

)

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ycl

ust

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Bip

olar

An

ym

ood

Su

bst

ance

use

/S

tud

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PD

AS

PD

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dis

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DD

dis

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Sch

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nia

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end

ence

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ne

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.126.

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.70.

77.

4(m

ild

and

seve

real

coh

olis

m)

Lor

ange

ret

al.8

11.7

(MR

)∗∗

6.4

(MR

)∗0.

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R)

0P

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.220.

8b6.

27.

7∗4.

61.

56.

2∗11

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lcoh

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/de

pen

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0.8

(opi

oid

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nce

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olof

f&

7.0

4.8∗

(“ec

cen

tric

/8.

7∗∗

2.6

11.8

(alc

ohol

ism

)M

illw

ard14

pecu

liar

beh

avio

r”)

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onet

al.9

17.9

(MR

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13.6

(alc

ohol

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ug

abu

se)

Lor

ange

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Tu

lis35

18.5

(MR

—al

coh

olis

m)∗∗

Sch

ulz

etal

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5016

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m)

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kset

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),9.

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al.11

24.9

(MR

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13.6

(MR

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R)

0.7

(MR

)23

.30

24.3

(MR

—al

coh

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10.7

(MR

—dr

ug

abu

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Rei

ch36

6.5

Sch

ulz

etal

.137.

5∗∗

15.3∗∗

1.5

(bip

olar

II)

4.6

15.3

(alc

ohol

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),∗∗

1.5

(dru

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use

)G

aspe

rin

iet

al.24

10.2

(MR

)S

ilve

rman

etal

.153.

121

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R)

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(MR

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(MR

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.9(M

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“alc

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(“m

anic

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”),6

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Joh

nso

net

al.37

10∗

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iso

etal

.2422

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25.9∗

1.9

29.6∗

25.9

(alc

ohol

abu

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depe

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),20

.4(d

rug

abu

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depe

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)

AS

PD

,an

tiso

cial

pers

onal

ity

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;BP

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alit

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DD

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pres

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diso

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;MR

,mor

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sk;S

TP

D,s

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alit

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ean

dco

llea

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did

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use

acl

assi

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syst

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ith

stan

dard

ized

diag

nos

tic

crit

eria

for

BP

D,i

nst

ead

empl

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gth

eco

nce

ptof

bord

erli

ne

pers

onal

ity

orga

niz

atio

n.

bP

ope

and

coll

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esre

port

edth

epr

eval

ence

ofdi

sord

ers

inre

lati

ves

ofB

PD

prob

ands

.Com

pari

son

sbe

twee

ngr

oups

wer

eex

amin

edon

lyfo

r“a

ny

clu

ster

B”

and

“an

ym

ood

diso

rder

.”∗ S

ign

ifica

ntl

ydi

ffer

ent

from

com

pari

son

grou

ps(p<

0.05

).∗∗

Sig

nifi

can

tly

diff

eren

tfr

omco

mpa

riso

ngr

oups

(p<

0.01

).

9

10 White et al.Harv Rev Psychiatry

January 2003

Within this literature, some authors have calculated mor-bidity risk (thereby approximating lifetime prevalence bycorrecting for the fact that not all relatives will have passedthrough the period of risk for development of a disorder),while others have simply reported prevalence at the time ofthe study. Because researchers have used widely differingmethods to estimate the morbidity risk of psychiatric disor-ders among relatives of probands with BPD, we concludedthat we could not calculate a meaningful combined estimateusing meta-analytic techniques. Rather, we simply reportthe estimates, note that they span a certain range, and com-pare them to those from population-based studies.4−7 Suchestimates can offer a first approximation of the true valuesand 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 thosethat are proposed as standards for conducting such research.Because the question of whether BPD is itself familial is soimportant, we focus on the nine studies that have consid-ered this issue. We conclude by highlighting the persistentquestions raised by this literature and identifying topics forfurther research.

SCHIZOPHRENIA SPECTRUM DISORDERS

The conceptualization of BPD in the 1970s as a schizophre-nia spectrum disorder was prompted in part by the broadconcept of schizophrenia in use at that time, by the signif-icance assigned to patients’ psychosis-like experiences, andby an adoption study in which persons labeled as having“borderline schizophrenia” were found to have a disorderthat was genetically linked to schizophrenia.1

Schizophrenia

Four8−11 of the eight studies that assessed schizophreniain relatives of BPD probands found no cases among theseindividuals. In the remaining four,12−15 the prevalence ofschizophrenia 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 comorbidfor STPD. This might explain the high risk for schizophre-nia among relatives in the two studies. Using an earlierdefinition of BPD, Soloff and Millward14 subdivided theirBPD sample into “unstable,” “schizotypal,” and “mixed” sub-groups. The “mixed” subgroup had a significantly higherprevalence of schizophrenia in relatives than did either ofthe other two subgroups. This clarification suggests thatit may be the STPD/BPD comorbidity, not STPD alone,that correlates with a high prevalence of schizophrenia inrelatives.

Schizotypal Personality Disorder

Soloff and Millward14 found a significantly higher preva-lence of “eccentric/peculiar” behavior in relatives ofprobands with BPD than in relatives of those with depres-sion or schizophrenia (p= 0.03). This, however, might alsobe attributable to their definition of BPD, which includedSTPD traits. Only Baron and colleagues9 examined theprevalence of STPD in relatives of BPD probands and usedSTPD 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 researchersfound a larger morbidity risk for BPD in relatives of normalcontrols than in relatives of STPD probands, and a greaterprevalence of STPD in relatives of normal probands than inrelatives of BPD probands.

In summary, these results do not uphold the hypothesisthat BPD is genetically linked to schizophrenia or STPD.Thus, there is little support for the concept of BPD as aschizophrenia spectrum disorder.

AFFECTIVE SPECTRUM DISORDERS

The nature of the relationship between BPD and de-pression has been the subject of much literature andcontroversy.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 Becausethe 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 increasinginterest.19−21

Mood Disorders

In the six studies assessing mood disorders in relatives ofBPD probands,9,11,12,22–24 prevalence ranged from 6.2%22 to50%.23 Two of the studies12,23 calculated risk for mood dis-orders in general, without differentiating between bipolarand unipolar conditions. They found a lifetime prevalenceof 20.7%12 and 50%.23 In studies that differentiated be-tween unipolar and bipolar disorders, MDD, rather thanbipolar disorder, accounted for most of the mood disorderprevalence11,15,22 (see Table 1).

Major Depressive Disorder

Ten studies assessed the prevalence or morbidity riskfor 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

Harv Rev Psychiatry

Volume 11, Number 1 White et al. 11

particularly low estimates from investigations using chartreviews.8,22 By comparison, a recent estimate∗ of the lifetimeprevalence of MDD in the general population of the UnitedStates 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 relativesof BPD probands than in relatives of “primary depressivedisorder” probands. The other24 found no significant differ-ences in relatives’ risk for MDD between the MDD and BPDproband groups.

Three studies8,13,24 showed that relatives of BPDprobands had a significantly higher prevalence of MDD thandid relatives of persons who had neither disorder. Two of thestudies8,13 found this to be true in comparison to relatives ofschizophrenia probands, and one24 found it to be true in com-parison to never-psychiatrically-ill controls but not to mooddisorder probands.

To determine whether an elevated prevalence of MDD inrelatives of BPD probands was due to the co-occurrence ofMDD in the BPD probands (since MDD is known to be famil-ial), three studies11,22,27 compared the prevalence of MDD inrelatives of “pure” BPD probands (i.e., individuals withoutcomorbid affective disorder) and relatives of BPD probandswith comorbid MDD. In all three investigations, relatives ofthe “pure” BPD group had a significantly lower risk for af-fective disorder than did relatives of the proband group withco-occurring BPD and MDD. These results have led previousreviewers15,16 to conclude that BPD and MDD are indepen-dent disorders that frequently co-occur.

This type of comparison can provide evidence that MDDin a proband with BPD is associated with a greater proba-bility that a relative will have MDD. However, it does notdirectly address the question of whether BPD and MDDcoaggregate within families (that is, whether the risk ofMDD is elevated in relatives of BPD probands and, con-versely, whether the risk of BPD is elevated in relatives ofMDD probands—independent of the familial aggregation ofMDD). The most informative determination in this regardfrom studies of BPD probands is whether the prevalence ofMDD without BPD is elevated in relatives of BPD probandswho do not have MDD. (See Hudson et al.28,29 for furtherdiscussion 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 usedonly to make very rough comparisons with the prevalences found inindividual studies. Such rates depend on many factors (e.g., demo-graphics, ascertainment, assessment methods) that may vary fromone 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 foundno differences in the prevalence of mood disorders betweenrelatives of BPD probands without MDD and relatives of119 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 roughlyequivalent to the 1.6% lifetime prevalence of bipolar disorderin the general population.26 These rates were no higher thanthose found in relatives of comparison group probands. Inthe two studies using comparison groups of bipolar disorderprobands,8,22 the rates for bipolar disorder in relatives of theBPD probands (with or without concurrent mood disorder)were nonsignificantly lower. In neither study was the rateof BPD increased in relatives of bipolar disorder probands.Thus there is no evidence suggesting a familial relationshipbetween the two disorders.

In summary, these results provide provocative but un-convincing evidence for a familial relationship of BPD withMDD, 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 spectrumdisorder derives from the many seemingly impulsive behav-iors that characterize BPD patients, including substanceabuse, violence, self-injurious acts, and disordered eating.3,30

The linkage of ASPD and substance abuse/dependenceas impulse spectrum disorders has been shown bothepidemiologically31 and genetically.32–34

Substance Use Disorders

Eleven studies9–15,22–24,35 calculated the lifetime prevalenceor morbidity risk for alcohol abuse or dependence in relativesof BPD probands. Estimates for risk in relatives ranged from7.4%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 accountfor the low prevalence found by Stone and colleagues.12 Nev-ertheless, this range appears to be somewhat higher than

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 alcoholabuse26—seen in the general population. The difference isgreater when the estimate is contrasted with the lifetimeprevalence rates for females, who comprise the majorityof most BPD samples—i.e., abuse, 6.4%; and dependence,8.2%.26

The prevalence of alcohol abuse was nonsignificantlyhigher in relatives of BPD probands than in those of normalcontrols.9,12,24 Two studies13,23 found prevalence of alcoholabuse or dependence to be significantly higher in relatives ofBPD probands than in relatives of schizophrenia probands.However, no researchers separated BPD probands with andwithout 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 maybe due to the well-documented familial aggregation of al-cohol abuse or dependence. Furthermore, no studies havelooked at the prevalence of BPD in probands with alcoholabuse/dependence.

Six studies calculated a prevalence of drug abuse ordependence in relatives of BPD probands; their estimatesranged from 0.8%22 to 20.4%.24 Lifetime prevalence in thegeneral population is 4.4% for abuse and 7.5% for depen-dence (3.5% and 5.9%, respectively, for females).26 Althoughtrends were detected toward more abuse in relatives of BPDprobands 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 aggregationof 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 probandsor relatives.10,11,13 The median prevalence of 7% is twicethat seen in the general population (3.5%26). Of the fivestudies that compared the prevalence of ASPD in rela-tives of BPD probands to the prevalence in relatives ofother probands,11,13–15,23 only Schulz and colleagues13 founda significant difference. ASPD was significantly more com-mon among the relatives of borderline probands withoutASPD than comparison probands—in this case, schizophre-nia probands without ASPD. Taken together, these resultssuggest 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 toASPD) rests largely on studies in which BPD probands werecompared to schizophrenia probands. It is possible that rel-atives of individuals with schizophrenia have an unusuallylow 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 spectrumdisorders.

BORDERLINE PERSONALITY DISORDER

Nine studies8–12,22,24,36,37 examined the occurrence of border-line psychopathology (by various definitions) in relatives ofBPD probands. Four of them8−11 reported lifetime morbidityrisk for BPD in relatives; five12,22,24,36,37 calculated only theunadjusted lifetime prevalence. The prevalence or morbidityrisk for BPD in relatives ranged from 0.8%22 to 24.9%.11 Epi-demiological studies4−7 indicate a 0.6–3% prevalence of BPDin the general population. Hence, the range reported heredemonstrates a 4- to 20-fold increase of BPD in relatives ofBPD probands compared to the general population. As notedin 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 thoseof comparison groups. Four8,9,11,37 of the six found a signifi-cantly higher prevalence or morbidity risk for BPD in therelatives of the BPD probands. The fifth36 found a trend(p= 0.07), but this result was derived from only 12 BPDprobands. The only investigation that did not find a higherprevalence of BPD among relatives of BPD probands12 wasconducted prior to the establishment of DSM criteria forBPD.

Three studies22,24,37 examined the prevalence of ClusterB disorders (which includes histrionic, antisocial, and nar-cissistic personality disorders, as well as BPD) in relatives ofBPD probands. All three had small numbers of probands andexpanded to include other Cluster B disorders to enhance thepower to detect coaggregation, at the cost of losing specificityfor 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 riskfor Cluster B disorders in relatives of BPD probands than inrelatives of never-psychiatrically-ill controls; they found asimilarly 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 theother two studies) found a low prevalence (7.7%) of ClusterB 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

Harv Rev Psychiatry

Volume 11, Number 1 White et al. 13

disorders observed in this review in relatives of BPDprobands suggests that certain traits within this cluster,such as affective instability or impulsivity, may aggregatewith BPD in families (see Discussion, below).

To examine the evidence for the familial aggregation ofBPD, we calculated ratio of the risk of BPD in relatives ofprobands with BPD versus the risk in relatives of probandswithout BPD. For this analysis, we included all studies thatmade BPD diagnoses of probands using DSM criteria by ei-ther chart review or structured interview, assessed BPD (orCluster B disorders) in relatives, and employed a compari-son group. For the estimate of risk, we used either the crudelifetime prevalence or the estimated morbidity risk. If bothmeasures could be calculated, we chose the morbidity riskbecause it represents a more accurate assessment of truerisk. The six studies shown in Table 28,9,11,22,24,37 met theseinclusion criteria for risk-ratio analysis.

To judge from these studies, BPD is consistently morecommon among the relatives of BPD probands than amongthe relatives of non-BPD probands. However, the differencesin diagnostic criteria for BPD, in the diagnoses of comparisongroups, in recruitment procedures, and in interview methodsof these studies may have substantially altered the “true”estimate of risk. Certainly this heterogeneity precludes asolid estimation of risk ratio using meta-analytic techniques.

METHODOLOGICAL ISSUES

In reviewing the methodological issues of the nine studies ofBPD’s familial aggregation,8−12,22,24,36,37 we follow the stan-dards for family risk studies established by Knowles andcolleagues38 and used by Dahl27 in 1994 on a portion of thisliterature. The methodological quality of the family studiesis assessed on the following variables: sample size, probanddemographic representativeness, and subject selection; di-agnostic criteria and assessment means (e.g., structured in-terview, questionnaire), and percentage of relatives directlyinterviewed (see Table 3).

Sample Size

In the nine studies reviewed here, the number of BPDprobands ranged from 11 to 83, and the number of relativesassessed 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. Allbut one of these studies employed indirect methods to as-sess at least some of the relatives. The exception was Reichand colleagues’ investigation,36 which assessed all availablerelatives (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 consistentwith the data; that is, the data cannot distinguish whetherthe “true” level of familiality is very large or very small.Second, it is difficult to compare the risks of disorders in therelatives of BPD probands with the risks in relatives of non-BPD probands. For example, suppose that the lifetime riskfor BPD among relatives of probands with BPD is 10%. Tohave 90% power to show that this risk is significantly greaterthan a 4% risk of BPD among relatives of another probandgroup 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 ofa type-II error (i.e., not detecting true differences betweengroups).

Representativeness

Five of the nine studies shown in Table 3 included both malesand females, over a wide age range, in their proband sam-ples. Loranger and colleagues8 had only females in theirBPD proband sample, and Johnson and coworkers37 in-cluded only adolescents. Because the relatives included bothmales and females over a wide age range, it is possible inprinciple to examine effects of age and gender. Althoughmost 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 certainconditions. The ascertainment for all studies except one9 in-volved selecting patients with BPD from either inpatientor outpatient settings. None attempted to locate individu-als with BPD who were not seeking treatment or a randomsample 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 secondmethod. Not surprisingly, the earliest family studies gen-erally had the weakest diagnostic methodology. Stone andcolleagues,12 for example, did not employ standardized diag-nostic criteria for BPD. The subsequent family studies haveall used DSM-based diagnostic criteria but have varied as towhich DSM system and which assessment instrument theyutilized. Loranger and colleagues8 selected probands using

14 White et al.Harv Rev Psychiatry

January 2003

TABLE 2. Family Studies of BPD Meeting Criteria for Assessment of Risk Ratios

RelativesProbands

At riska BPD Morbidity Risk ratioStudy Diagnostic method Group type n n (n) casesb risk (%)c (95% CI)

Loranger et al.8 DSM-III criteria Inpatientsretrospectively applied BPD 83 338 249 29 11.65to 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 7.7to 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 OutpatientsBPD 48 240 177 44 24.9ASPD 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 InpatientsBPD ? 39 4 10.3AVPD ? 62 2 3.2 3.2 (.61, 17)No PD 17 46 0 0

Riso et al.24,f PDE OutpatientsBPD 11 54 12 22.2Mood 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 forInterviewing 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 thereforedid 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 Stromgren 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 otherwisespecified, rather than specifically for BPD). As noted earlier,Loranger and colleagues8 and Pope and coworkers22 usedchart review to assess both probands and relatives. In Baronand colleagues’ sample,9 15 of the 17 BPD probands had“probable” BPD. Reich36 measured Axis II in probands andrelatives with the Personality Diagnostic Questionnaire, aninstrument 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 structuredinterviews to establish the proband diagnoses, DSM crite-ria have changed over the years, and only Zanarini andcolleagues11 confirmed the diagnosis using a second method.Axis I assessment has also progressed over time, fromunstructured methods,8,12,22 to the Schedule for Affective

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16 White et al.Harv Rev Psychiatry

January 2003

Disorders and Schizophrenia,9,10 to the Structured ClinicalInterview for the DSM,11,24,36,37 an instrument that assessesall Axis I diagnoses.

Rater Reliability and Blindness

As shown in Table 3, there is an obvious progression inthe 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 membersincluded 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’sdiagnosis. Interrater reliability was recorded in only fourstudies.8,9,25,37

Direct versus Indirect Assessment

Although family history (relying primarily on the proband’sreport) and family study (relying primarily on direct in-terviews of relatives) usually produce similar results, di-rect interviews remain the standard for establishing validdiagnostic 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 andavoid unidentifiable reporting biases,43 resulting in a higherprevalence.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). InBaron and colleagues’ investigation,9 70% of the relativesof normal control probands but none of the relatives of BPDand STPD probands received direct interviews. Johnson andcoworkers37 and Riso and colleagues24 reported no differ-ence between BPD and comparison groups in the propor-tion of relatives who were directly interviewed. Stone andcoworkers12 did not mention whether there was a signifi-cant difference among their groups in number of relativesdirectly interviewed. No studies indicated whether relativesrefused participation or how many declined to have directinterviews.

The two studies that found the highest risk for BPD inrelatives (24.9%11 and 17.9%9) relied solely on indirect in-terviews when obtaining information on relatives of BPDprobands. Moreover, Links and colleagues10 reported a BPDprevalence of 3.4% when relatives were interviewed directlybut 15.1% when indirect methods were employed. To com-pensate for the expectation of false negatives from indirectassessments, 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 thosedirectly interviewed had to meet all seven. Of note, Baronand coworkers9adopted a similar compensatory strategy andfound significant differences in prevalence of BPD in rela-tives only after making this correction. These results suggestthat the reported risk for BPD in relatives may increasewith 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 tothe relatives’ underreporting. This explanation might alsohold true for BPD—i.e., relatives with BPD might under-report their symptoms when directly interviewed, possiblybecause of denial or fear of stigma, thereby causing falsenegatives. Conversely, when indirect methods are used, BPDprobands might exaggerate BPD features among their rela-tives, thereby causing false positives. The latter explanationis consistent with the tendency of persons with BPD to de-value or vilify members of their family.47 An implication ofthis review is that future family studies should incorporateboth direct and indirect methods, as Links and colleagues10

did, comparing the frequencies of BPD determined with eachmethod and exploring reasons for the differences.44

Comparison Groups

Proper selection of comparison groups is an essential featureof 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 BPDand are derived from the same population source (e.g., hos-pital, community) that gave rise to BPD cases, but do nothave BPD. The comparison group(s) and the BPD probandsshould have the same distribution of any variables that couldinfluence risk of BPD, including all forms of psychopathol-ogy (see Wacholder et al.48). Only three studies,9,24,36 all ofwhich used “normals” as a comparison group, came close tofulfilling 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 examinepatterns of coaggregation of BPD with other disorders infamilies. They are less useful in assessing the family aggre-gation of BPD itself, because it is possible that relatives ofprobands with a condition other than BPD, such as a mooddisorder, may have an elevated prevalence of BPD comparedto relatives of probands with neither BPD nor mood disorder.

The ideal family study would include comparison groupsthat 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 studieshave changed over the years. As noted, most of the earlier

Harv Rev Psychiatry

Volume 11, Number 1 White et al. 17

studies compared BPD probands to probands with Axis Idisorders—i.e. schizophrenia or mood disorders. No stud-ies, however, have included comparison groups consisting ofprobands with substance abuse or eating disorders, whichare suspected to be familial. Two studies have used person-ality disorder comparison groups—i.e., avoidant personalitydisorder37 and ASPD.11 Of these, only the latter can be saidto be a truly near-neighbor comparison group.

Comparability of basic demographic features that mightinfluence prevalence of disorders can be achieved either bymatching or by statistical control. In only two9,24 of the tenstudies reviewed were comparison group probands matchedby age, sex, and race; in another four,8,11,12,37 demographicsimilarities and differences were identified, but whethergroups matched was not reported.

DISCUSSION

A significant amount of research has been published on thefamiliality of BPD and its coaggregation with other disor-ders. As noted above, these studies have generally supportedthe idea that BPD “breeds true.” However, major problemsexist in the quality of the methodology employed in theseinvestigations. The fact that no adequately sized study us-ing direct assessments of relatives has been conducted forBPD contrasts dramatically with the fact that by 1995, thismethod had been utilized in ten studies of mood disorders,eight of anxiety disorders, nine of schizophrenia, and five ofalcohol abuse/dependence.49 In the absence of such an in-vestigation for BPD, Dahl’s conclusion27 in 1994 that BPD’sfamiliality 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 forresearch examining both genetic and environmental under-pinnings of the disorder. Family studies, done well, couldhelp to clarify which traits are transmitted.

The existing studies investigating BPD’s coaggregationwith 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 theuse of an alternative strategy—i.e., following Silverman andcolleagues’ approach15 and examining the familial aggrega-tion of BPD component traits, such as affective instabilityand 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 andcolleagues51 have proposed that emotional dysregulation isthe core aspect of the BPD construct; in their genetic fac-tor analysis, this dimension seemed to account for much ofthe genetic variance. Such investigations suggest that thecomponent 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 impulsivetraits, as well as other BPD characteristics such as aggres-sivity and unstable interpersonal relationships, aggregateindividually or coaggregate with other traits in families.As noted, the evidence for increased Cluster B disorders infamilies of BPD probands also supports the value of sucha study. We would hypothesize that individuals with BPDshare the histrionic personality disorder trait of affective in-stability; those with ASPD share BPD traits of impulsivityand aggressivity; and those with narcissistic personality dis-order share the BPD trait of interpersonal instability. Sucha model predicts that persons with any of these personalitydisorders are likely to have relatives with similar traits, butthat to develop BPD requires a combination of several suchtraits.

REFERENCES

1. Siever LJ, Gunderson JG. Genetic determinants of borderlineconditions. Schizophr Bull 1979;5:59–86.

2. Akiskal HS. Subaffective disorders: dysthymic, cyclothymic andbipolar II disorders in the “borderline” realm. Psychiatr ClinNorth Am 1981;4:25–46.

3. Zanarini MC. Borderline personality disorder as an impulsespectrum disorder. In: Paris J, ed. Borderline personalitydisorder: etiology and treatment. Washington, DC: AmericanPsychiatric Press, 1993:67–85.

4. Torgersen S, Kringlen E, Cramer V. The prevalence of person-ality disorders in a community sample. Arch Gen Psychiatry2001;58:590–6.

5. Lenzenweger MF, Loranger AW, Korfine L, Neff C. Detectingpersonality disorders in a nonclinical population: application ofa 2-stage procedure for case identification. Arch Gen Psychiatry1997;54:345–51.

6. Swartz M, Blaser D, George L, Winfield I. Estimating the preva-lence of borderline personality disorder in the community. J Per-sonal Disord 1990;4:257–72.

7. Weissman MM. The epidemiology of personality disorders: a1990 update. J Personal Disord 1993;7(suppl):44–62.

8. Loranger AW, Oldham JM, Tulis EH. Familial transmission ofDSM-III borderline personality disorder. Arch Gen Psychiatry1982;39:795–9.

9. Baron M, Gruen R, Asnis L, Lord S. Familial transmissionof schizotypal and borderline personality disorders. Am JPsychiatry 1985;142:927–34.

18 White et al.Harv Rev Psychiatry

January 2003

10. Links PS, Steiner M, Huxley G. The occurrence of border-line personality disorder in the families of borderline patients.J Personal Disord 1988;2:14–20.

11. Zanarini MC, Gunderson JG, Marino MF, Schwartz EO,Frankenburg FR. DSM-III disorders in the families of border-line outpatients. J Personal Disord 1988;2:292–302.

12. Stone MH, Kahn E, Flye B. Psychiatrically ill relatives ofborderline patients: a family study. Psychiatr Q 1981;53:71–84.

13. Schulz PM, Soloff PH, Kelly T, Morgenstern M, Franco DR,Schulz SC. A family history study of borderline subtypes.J Personal Disord 1989;3:217–29.

14. Soloff PH, Millward JW. Psychiatric disorders in the families ofborderline patients. Arch Gen Psychiatry 1983;40:37–44.

15. Silverman JM, Pinkham L, Horvath TB, Coccaro EF, Klar H,Schear S, et al. Affective and impulsive personality disordertraits in the relatives of patients with borderline personalitydisorder. Am J Psychiatry 1991;148:1378–85.

16. Gunderson JG, Phillips KA. A current view of the interfacebetween borderline personality disorder and depression. Am JPsychiatry 1991;148:967–75.

17. Gunderson JG, Triebwasser J, Phillips KA, Sullivan CN. Per-sonality and vulnerability to affective disorders. In: CloningerCR, ed. Personality and psychopathology. Washington, DC:American Psychiatric Press, 1999:3–32.

18. Koenigsberg HW, Anwunah I, New AS, Mitropoulou V, SchopickF, Siever LJ. Relationship between depression and border-line personality disorder. Depression Anxiety 1999;10:158–67.

19. Blacker D, Tsuang MT. Contested boundaries of bipolar disor-der and the limits of categorical diagnosis in psychiatry. Am JPsychiatry 1992;149:1473–83.

20. Kopacz DR, Janicak PG. The relationship between bipolardisorder and personality. Psychiatr Ann 1996;26:644–50.

21. Bolton S, Gunderson JG. Distinguishing borderline personalitydisorder from bipolar disorder: differential diagnosis and impli-cations. Am J Psychiatry 1996;153:1202–7.

22. Pope HG Jr, Jonas JM, Hudson JI, Cohen BM, Gunderson JG.The validity of DSM-III borderline personality disorder: a phe-nomenologic, family history, treatment response, and long-termfollow-up study. Arch Gen Psychiatry 1983;40:23–30.

23. Schulz PM, Schulz SC, Goldberg SC, Ettigi P, Resnick RJ,Friedel RO. Diagnoses of the relatives of schizotypal outpa-tients. J Nerv Ment Dis 1986;174:457–63.

24. Riso LP, Klein DN, Anderson RL, Ouimette PC. A family studyof outpatients with borderline personality disorder and nohistory of mood disorder. J Personal Disord 2000;14:208–17.

25. Gasperini M, Battaglia M, Scherillo P, Sciuto G, Diaferia G,Bellodi L. Morbidity risk for mood disorders in the families ofborderline patients. J Affect Disord 1991;21:265–72.

26. Kessler RC, McGonagle KA, Zhao S, Nelson CB, Hughes M,Eshleman S, et al. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States: results from theNational Comorbidity Survey. Arch Gen Psychiatry 1994;51:8–19.

27. Dahl AA. Heredity in personality disorders—an overview. ClinGenet 1994;46:138–43.

28. Hudson JI, Laird NM, Betensky RA. Multivariate logistic re-gression for familial aggregation of two disorders, I: Develop-ment of models and methods. Am J Epidemiol 2001;153:500–5.

29. Hudson JI, Laird NM, Betensky RA, Keck PE Jr, Pope HG Jr.Multivariate logistic regression for familial aggregation of twodisorders, II: Analysis of studies of eating and mood disorders.Am J Epidemiol 2001;153:506–14.

30. Van Reekum R, Links PS, Boiago I. Constitutional factors in bor-derline personality disorder: genetics, brain dysfunction, andbiological markers. In: Paris J, ed. Borderline personality dis-order: etiology and treatment. Washington, DC: American Psy-chiatric Press, 1993:13–38.

31. Krueger RF. The structure of common mental disorders. ArchGen Psychiatry 1999;56:921–6.

32. Grove WM, Eckert ED, Heston L, Bouchard TJ Jr, Segal N,Lykken DT. Heritability of substance abuse and antisocialbehavior: a study of monozygotic twins reared apart. BiolPsychiatry 1990;27:1293–304.

33. Pickens RW, Svikis DS, McGue M, LaBuda MC. Commongenetic mechanisms in alcohol, drug, and mental disordercomorbidity. Drug Alcohol Depend 1995;39:129–38.

34. Slutske WS, Heath AC, Dinwiddie SH, Madden PA, Bucholz KK,Dunne MP, et al. Common genetic risk factors for conduct disor-der and alcohol dependence. J Abnorm Psychol 1998;107:363–74.

35. Loranger AW, Tulis EH. Family history of alcoholism in bor-derline personality disorder. Arch Gen Psychiatry 1985;42:153–7.

36. Reich JH. Familiality of DSM-III dramatic and anxious person-ality clusters. J Nerv Ment Dis 1989;177:96–100.

37. Johnson BA, Brent DA, Connolly J, Bridge J, Matta J,Constantine D, et al. Familial aggregation of adolescentpersonality disorders. J Am Acad Child Adolesc Psychiatry1995;34:798–804.

38. Knowles JA, Kaufmann CA, Rieder RO. Genetics. In: HalesRE, Yudofsky SC, Talbot JA, eds. American Psychiatric Presstextbook of psychiatry. 3rd ed. Washington, DC: AmericanPsychiatric Press, 1999:35–82.

39. Hyler SE, Skodol AE, Oldham JM, Kellman HD, Doidge N.Validity of the Personality Diagnostic Questionnaire—Revised:a replication in an outpatient sample. Compr Psychiatry1992;33:73–7.

40. Andreasen NC, Endicott J, Spitzer RL, Winokur G. The familyhistory method using diagnostic criteria: reliability and validity.Arch Gen Psychiatry 1977;34:1229–35.

41. Andreasen NC, Rice J, Endicott J, Reich T, Coryell W. The fam-ily history approach to diagnosis: how useful is it? Arch GenPsychiatry 1986;43:421–9.

42. Heun R, Maier W, Muller H. Subject and informant variablesaffecting family history diagnoses of depression and dementia.Psychiatry Res 1997;71:175–80.

43. Kendler KS, Silberg JL, Neale MC, Kessler RC, Heath AC,Eaves LJ. The family history method: whose psychiatric historyis measured? Am J Psychiatry 1991;148:1501–4.

44. Faraone SV, Tsuang MT. Methods in psychiatric genetics. In:Tsuang MT, Tohen M, Zahner GEP, eds. Textbook in psychiatricepidemiology. New York: Wiley-Liss, 1995:81–134.

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Volume 11, Number 1 White et al. 19

45. Mendlewicz J, Fleiss JL, Cataldo M, Rainer JD. Accuracy ofthe family history in affective illness: comparison with directinterviews in family studies. Arch Gen Psychiatry 1975;32:309–14.

46. Orvaschel H, Thompson WD, Belanger A, Prusoff BA, Kidd KK.Comparison of the family history method to direct interview:factors affecting the diagnosis of depression. J Affect Disord1982;4:49–59.

47. Perry JC, Herman JL, Van der Kolk BA, Hoke LA. Psychother-apy and psychological trauma in borderline personality disor-der. Psychiatr Ann 1990;20:33–43.

48. Wacholder S, McLaughlin JK, Silverman DT, Mandel JS. Se-lection of controls in case-control studies, I: Principles. Am JEpidemiol 1992;135:1019–28.

49. Merikangas KR, Swendsen JD. Genetic epidemiology of psychi-atric disorders. Epidemiol Rev 1997;19:144–55.

50. Torgersen S, Lygren S, Øien PA, Skre I, Onstad S, Edvardsen J,et al. A twin study of personality disorders. Compr Psychiatry2000;41:416–25.

51. Livesley WJ, Jang KL, Vernon PA. Phenotypic and geneticstructure of traits delineating personality disorder. Arch GenPsychiatry 1998;55:941–8.