genetics of patients with borderline personality disorder

BORDERLINE PERSONALITY DISORDER 019%953X/OO $15.00 + .OO

GENETICS OF PATIENTS WITH BORDERLINE PERSONALITY

DISORDER

Svenn Torgersen, PhD

Many clinicians have held the view that borderline personality disorder (BPD) is solely or mainly the product of environmental risks, ranging from aversive childhood experiences to organic trauma, but Kernbergs proposed that the basic core in the development of BPD organization may be an inherited, unusually strong, aggressive drive associated with an inborn deficiency in the ability to tolerate anxiety. Linehan and Koerner” suggested that the basis for BPD is an inherited biological predisposition to emotional dysregulation. This dysregulation implies an accentuated sensitivity to emotional stimuli; intense reactions to such stimuli; and a slow, delayed return to a normal emotional level. Dysregulation means a lack of the ability to control impulsive behavior related to strong positive and negative effects, a lack of ability to comfort oneself when strong effects give intense physiologic outcomes, problems in turning attention toward other aspects, and difficulties in organizing and coordinating activities to achieve one’s goals.

These investigators did not imply that biology is the only determi- nant. Linehan and Kramer’l suggested that an invalidating childhood environment is also necessary for the development of BPD. To determine whether BPD is influenced by genetic factors, a series of systematic empiric studies must be reviewed.

From the Center for Research in Clinical Psychology, University of Oslo, Oslo, Norway

THE PSYCHIATRIC CLINICS OF NORTH AMERICA

VOLUME 23 * NUMBER 1 MARCH 2000 1

2 TORGERSEN

GENETIC METHODS

To decide whether and to what extent genetic factors are of importance in the development of personality disorders, several options exist. A classic method involves studying whether the disorder runs in families, but this approach can show only that a disorder is influenced by heredity and common family environmental factors, not heredity only. Family members can be concordant for a disorder because of common genes, common family environmental factors, or both.

The twin method makes it possible to separate the effect of genes from the effects of common environment. The difference between in- terpair correlations in monozygotic (MZ) and dizygotic (DZ) pairs measures the effect of heredity. The residual environmental variance can then be classified into ”common” or ”shared environment versus “unique” or “unshared environment. The extent to which the intrapair correlation in DZ pairs is greater than half of the MZ correlation also reflects the extent of common environment, but the twin method has disadvantages, including that it rests on ”the equal environment assumption,” which means that the environment is assumed to be alike for MZ and DZ twins.

Another method involves adoption studies, through which the effects of environment can be more clearly separated from the effects of genes, but nonadditive genetic effects are difficult to determine with this method. The most powerful approach involves combining twin and adoption methods by studying twins reared apart. If twins are separated at birth, the problem of the higher similarity of the environment of MZ twins living together in childhood compared with DZ twins is elimi- nated. Few twin pairs are separated by birth, however. When studying a rare disorder, such as BPD, it is lucky to find a few.

Recently, molecular genetic methods have made possible the more direct study of genes. By means of advanced techniques, which chromo- some has a locus of gene coding associated with a mental disorder can be established. Mutant genes can be directly detected, increasing the likelihood of a certain kind of behavior or disorder.

As more studies apply these methods, physicians will become more sure about the effects of genes on the development of personality disorders. But because few studies have been conducted on BPD, research providing indirect information about the effects of genes on the development of BPD are reported.

Personality Traits Coinciding with Borderline Personality Disorder

Some studies have investigated correlations between the ”big five” personality factors (i.e., the five-factor model; FFM) and BPD.5, 29 The FFM describes five broad factors: (1) neuroticism, (2) extraversion, (3) openness to experience, (4) conscientiousness, and (5) agreeableness.

GENETICS OF PATIENTS WITH BORDERLINE PERSONALITY DISORDER 3

Table 1 shows the results of three of these studies, applying two structured interviews and four questionnaires aimed to measure BPD. Neuroticism is uniformly highly correlated with BPD, with a median correlation of 0.50. Conscientiousness gives also relatively similar results in different studies, with a moderate median correlation of - 0.23. Agree- ableness varies a little more, with a median of -0.24, whereas the correlations for extraversion and openness to experience are approximately zero, with a median of 0.05 and 0.04, respectively. The multiple regression correlation varies between 0.53 and 0.76, with a median of 0.69. Based on the median correlation, nearly half the variance in BPD is explained by the FFM. To the extent that the ”big five” coincide with BPD, the results of genetic analyses of the FFM factors can elucidate on the genetics of BPD.

Studies of twins reared apart show that neuroticism; to a lesser extent, conscientiousness; and to a moderate degree, agreeableness are all influenced by genes (Table 2).3,18 In addition, Tellegen’s dimension of negative affectivity, which is similar to neuroticism, and that of constraint, which is similar to conscientiousness, also have heritable compo- nents.26

A research team established in two samples that individuals scoring high on a dimension similar to neuroticism have the short variant of a gene that codes for serotonin reuptake.’O This polymorphism accounts for 3% to 4% of the total variation and 7% to 9% of the inherited variance. In a similar study, another research team found a gene that influences the likelihood of scoring high on novelty seeking or low on conscientiousness.2 Even if a low percentage of the total variance in personality dimensions is explained in this way, these studies may be the first step in the direct mapping of the genes responsible for variation in personality and for personality disorders.

Deviant Personality Traits Similar to Aspects of Borderline Personality Disorder

Using a thorough factor-analytic method, Livesley et all3 empirically described 18 personality dimensions accounting for many of the abnor- malities associated with personality disorders. Among these, the follow- ing traits are similar to aspects of BPD (subtraits are in parentheses): affective lability (affective instability and over-reactivity, generalized hypersensitivity, labile anger, and irritability); cognitive distortion (depersonalization, schizotypal cognition, and brief stress psychosis); identity problems (anhedonia, long-term feelings of emptiness, labile self- concept, and pessimism); insecure attachment (separation protest, secure base, proximity seeking, feared loss, and inability to tolerate solitude); and self-harm (ideas of self-harm and self-damaging acts). Affective lability, identity problems, and insecure attachment, traits characteristic

Tabl

e 1.

CO

RR

ELA

TIO

NS

BE

TWE

EN

PE

RS

ON

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TY D

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NS

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S A

ND

PE

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TY D

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SS

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sure

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0

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C

R

SID

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ull (

1992

)29

0.48

0.

04

- 0.

08

- 0.

46

- 0.

31

0.65

PD

E So

ldz

et a

1 (1

993)

= 0.

42

0.06

0.

20

- 0.

13

-0.1

0 0.

53

MM

PI

Trul

l (19

92)2

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0.69

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1992

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0.60

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0.76

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ian

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) (-

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)

N =

neu

rotic

ism

; E =

ext

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n; 0

= o

penn

ess

to e

xper

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= a

gree

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ness

; C =

con

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= m

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DE

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erso

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MM

PI =

Min

neso

ta M

ultip

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Per

sona

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ntor

y; M

CM

I =

Mill

on M

ultia

xial

In

vent

ory;

PD

Q-R

= P

erso

nalit

y D

isor

der Q

uest

ionn

aire

-Rev

ised

.


Table 2. GENETIC, COMMON FAMILY, AND UNIQUE ENVIRONMENTAL VARIANCE IN DIFFERENT PERSONALITY DIMENSIONS*

~~

Variances*

Common Unique Personality Dimension Genetic Family Environmental

Neuroticismt 0.31 (0.44) 0.10 (0.14) 0.58 (0.42) Negative affectivityt 0.55 (0.61) 0.02 (0.02) 0.43 (0.37) Agreeableness§ 0.12 (0.17) 0.21 (0.30) 0.57 (0.53) Conscientiousness5 0.29 (0.41) 0.11 (0.16) 0.60 (0.43) Constraint$ 0.58 (0.64) 0.00 (0.00) 0.43 (0.42)

*The numbers in parentheses are corrected for reliability defiency. tStudy: Pedersen et a1 (1991)1” SStudy: Tellegen et a1 (1988y6 §Study: Bergeman et a1 (1993)”

of BPD, also load on a higher-order factor called lability or emotional dysregu la tion.

The investigators found that the subtraits, traits, and higher-order dimensions show a heredity of approximately 0.40 to 0.50. Note that higher reliability emerges when more items are included in the measure- ment of the ~oncept .~ As in most behavioral genetic studies of personality, environmental variance was almost entirely unshared. Common family environment variance was observed for only two subtraits- depersonalization and self-damaging acts.7

In a later article,l4 a genetic factor analysis using an oblimin rotation confirmed the presence of four broad factors in personality: (1) inhibi- tion, (2) emotional dysregulation, (3) disocial behavior, and (4) compul- sivity. Strikingly, the phenotypic, genetic, and environmental factors were all convergent.

Examining residual heritability (separate from the higher-order factors), affective lability, identity problems, and insecure attachment all had genetic variance of approximately 0.40. Cognitive dysregulation fitted a model in which common environmental variance played some role7 so that this trait, associated with depersonalization, may be more influenced by family environment than other aspects of BPD. Self-harm was not included because of low item endorsement.

Livesley et all4 proposes that the dimension of emotional dysregulation or lability is the core aspect of the BPD construct. In the study just discussed, much of the genetic variance seems to be accounted for by this single, broad dimension, but more narrow traits had a residual heritability so that more specific facets of borderline personality may have specific genetic inheritance.

This line of research seems to indicate that BPD traits are, at least partly, inherited, but the extent to which personality questionnaires, such as those developed by Livesley et al, measure BPD as defined

6 TORGERSEN

by DSM-IV or ICD-10 is uncertain. In general, correlations between questionnaires and interview measures for personality are not high.3l

STUDIES OF BORDERLINE PERSONALITY DISORDER

Family Studies

Several studies have investigated whether BPD runs in families.’, 12,

15, 19, 20, 22, 24, 29 The frequency of borderline personality disorder, or BPD features, among first-degree relatives of probands varies among studies. This is not strange because the definitions of BPD-like syndromes are somewhat different in each report.

Loranger et al,15 Zanarini et al,30 and Silverman et alZ2 all found statistically significant differences between relatives of individuals with BPD and relatives of controls, but most research teams have not directly interviewed relatives, with the exception of Links et a1,12 Baron et al,‘ and ReichZo (for part of the sample). For example, Loranger et all5 reviewed medical records in which the information about relatives stemmed from the proband’s therapist and social worker. The criteria used for BPD traits among the relatives were closer to those of antisocial personality disorder and substance abuse disorder than BPD, and only two of nine criteria were required. Thus, the study demonstrated ”so- cially” negative reports about the relatives of individuals with BPD, but whether more of them had DSM-111-defined BPD than controls is unknown.

In another study, Soloff and MillwardZ4 did not measure BPD among relatives but rather what they called “eccentric or peculiar behavior,” in other words, personality features more similar to schizotypal personality disorder than to BPD. Silverman et alZ2 made the interesting observation that among the relatives, impulsive or affective personality traits (not mood disorders) were found but not both sets of personality traits.

Baron et all have often been cited as having found that BPD breeds true in families, but they obtained significance only when they included probable BPD and “corrected upward the frequency as a compensation for not having interviewed the relatives directly. Baron et all also showed that the frequency of BPD is especially low when the probands have mixed BPD plus schizotypal personality disorder.

A study by Zanarini et a130 offered strong evidence for familial transmission of BPD, but all information about these relatives stemmed from the patients with BPD.

Depending on patient reports in the study of the inheritance of BPD alone may not suffice. This fact is clearly shown by the findings of Links et a1,12 who reported a frequency of 3.4% for BPD when the relatives were interviewed directly and 15.1% based on information from patients. Thus, BPD probands may exaggerate BPD features among their relatives. No other patient group has such a negative view of their parents.


Twin Studies

Only one study of BPD inheritance using twin methodology has been published.28 In a Norwegian sample of 7 MZ and 18 DZ twin pairs, concordances of zero in MZ and 11% in DZ pairs were The prevalence of BPD is 1% to 2% in the general pop~lation.~, 6, 9, 16, 17, 25, 32

This study might seem to suggest that environment, not heredity, is of greater importance in the development of BPD, but the small sample size in this twin study makes a wrong conclusion easy to determine.

A much larger Norwegian twin studyz8” suggested that the genetic effect in the development of BPD is considerable. The results indicated that the genetic portion of the variance approached 0.70.

SUMMARY

An overview of the existing literature suggests that traits similar to BPD are influenced by genes. It is too early to say to what extent BPD is also influenced by genes, but because personality traits generally show a strong genetic influence, this should also be true for BPD.

Nonetheless, if the equal-environment assumption were to be vio- lated for MZ and DZ pairs, twin studies may be overestimating genetic effects and hiding the effect of common family environment. The less- than-ideal reliability of measurements used in this research may also reduce the effects of genes and common environment while increasing the effects of unique or nonshared environment.

The effect of genes on the development of BPD is likely substantial. The effect of common family environment may be close to zero. More studies, large and small, are needed to reach firmer conclusions about the influence of genetics on BPD.

References

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8 TORGERSEN

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Address reprint requests to Svenn Torgersen, PhD

P.O. Box 1039 Blindern University of Oslo

N-0317, Oslo Norway

e-mail: svenn.torgersen8psykologi.uio.no

genetics of patients with borderline personality disorder

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