Biological Underpinnings of Borderline Personality Disorder.pdf

Biological Underpinnings of Borderline

Personality Disorder

Marianne Goodman

Joseph Triebwasser

Antoaia New

SUMMARY. Biological understanding of a personality disorder is best

achieved by examining the disorder's component dimensions, which for

borderline personality disorder include impulsive aggression and affec-

tive instability. Current biological research into BPD aims to identify the

neurotransmitters and brain regions implicated in each of these key do-

mains. Because of advancing technologies and analytic strategies, struc-

tural and functional neuroimaging are at the forefront of such efforts.

Structural neuroimaging, primarily in the form 6f magnetic resonance

imaging (MRI) scans, gives information about the anatomy of the brain,

while functional neuroimaging, primarily functional MRI (fMRI) and

positron emission tomography (PET) scans, gives infortnation about

brain activity and neurotransmitter systems at the molecular level. BPD

neuroimaging studies to date have implied the involvement of several

neurotransmitter systetns, principally serotonin, along with dysfunction

of select brain regions, including the prefrontal cortex and amygdala,

suggesting a "dual-brain pathology": "hyperarousal-dyscontrol syn-

drome." However, the exact mechanisms of all these putative etiologies

remain unknown, doi: 10.1300/J200v06n01_04 [Article copies available for a

fee from The Haworth Document Deliver)' Service: 1-800-HAWORTH. E-nmil

[Haworlh co-indexing entry note]; "Biological Underpinnings of Borderline Personality Disorder."

Goodman, Marianne, Joseph Triebwasser, and Antonia New. Co-published simultaneously in Social Work in

Menial Health (The Haworth Press) Vol. 6, No. 1/2, 2008, pp. 33-47; and: Borderline Personality Disorder:

Meeting the Challenges to Successful Treatment (ed: Perry D. Hoffman, and Penny Steiner-Grossman) The

Haworth Press, 2008, pp. 33-47. Single or multiple copies of this article are available for a fee from The

Haworth Document Delivery Service [1-800-HAWORTH, 9:00 a.m. - 5:00 p.m. (EST). E-mail address:

docdelivery@haworthpress.coni].

Available online at http://swmh,haworthpress,com

doi:10.1300/J200v06n01 04

BORDERLINE PERSONALITY DISORDER

actdress: <dxxleli\ieiy@lmvoitly}w.^.com> Website: <ltttp://www.HaworthPress.com>

KEYWORDS. Personality disorder, borderline personality disorder,

impulsive aggression, affective instability

THE DIMENSIONAL APPROACH

TO PERSONALITY DISORDERS

In a landmark paper, Siever and Davis (1991) proposed a ditnen-

sional approach to the study of personality disorders. The core vulnera-

bilities that they argued contribute to characterological dysfunction

included affective instability/sensitivity, irnpulsivity, aggression and

cognitive/perceptual disttirbances. With some modifications, and al-

lowing for differences of opinions among vatious researchets, Siever

and Davis's formulation of the dimensions of personality has continued

to inform our understanding of both temperament and the Axis II diag-

noses that represent the most severe forms of personality pathology.

Recent research that has brought into question the stability and bound-

aries of the borderline diagnosis has lent suppott to the application of this

dimensional approach to borderline personality disorder. Longitudinal

studies of BPD in a non-clinical sample show only moderate stability

(.28-.62) over a two-year period (Trull et al., 1998). Cross-sectional studies

of personality disotdered populations show a high degree of co-morbidity

among these disorders, particularly between BPD and paranoid (14.5%),

schizotypal (14.3%), histrionic (13.5%) narcissistic (16.0%) and passive

aggressive (13.4%) petsonality disorders. This co-morbidity among and

within clusters also undercuts the distinctness of the three personality dis-

order clusters posited by DSM-IV (Watson et al., 1998).

Factor analyses of the phenomenology of BPD further suggest that a

dimensional approach may be more appropriate than the categorical

model that underlies the DSM, with impulsive aggression, affective in-

stability, and identity disturbance the core dimensions of the disorder

(Blais et al., 1997). A factor analysis of DSM-III-R criteria for BPD has

suggested that impulsivity and affective instability, along with a relat-

edness factor, comprise the three homogenous factors underlying the

condition (Sanislow et al., 2000); a subsequent, larger multi-center lon-

gitudinal study (Sanislow et al., 2002) has provided further evidence for

this formulation.

Goodman. Triebwasser, and New

35 .

Neuroendocrine findings, too, have tended to lend credence to the va-

lidity of the dimensional rather than categorical model of BPD, as have

heritability data: monozygotic-dizygotic twin studies suggest that while

personality disorder diagnoses themselves are not heritable, the traits of

impulsive aggression or assertive aggtessiveness are (Alnaes et al.,

1989; Coccaro et al., 1993; Torgersen et al., 1994).

Our current understanding of the neuroanatomic citcuitry and

neuromodulators involved in the key dimensions of BPD is described in

Figure 1. The dimensions of impulsivity, aggression and affective insta-

bility have been studied most extensively and will therefore be the focus

of the remainder of this review.

IMPULSIVE AGGRESSION IN BPD

Phenomenology

Individuals with BPD often require psychiatric attention because of

their difficulty with behavioral control and manifest a spectrum of im-

pulsive aggressive acts, such as violence and assault, spousal abuse,

property damage, self-mutilation and suicide attempts (Hamberger et

al., 1986; Mikolajczak et al., 1978), resulting in difficulty in maintain-

ing jobs (Skodol et al., 2005) and disrupted family relationships. As

pharmacological and other treatments for mood disorders and psychotic

disorders have improved, an increasing proportion of psychiatric hospi-

talizations ate precipitated by an actual or threatened act of aggression

directed towards self or others in patients with a primary personality

diagnosis (Hansson et al., 1989; Breslow et al., 1993; Molinari et al.,

1994).

Neuroendocrine Studies

Abnormalities in central serotonergic activity have consistently been

found to be associated with measures of impulsive aggression in pa-

tients with personality disorders, including BPD (Coccaro et al., 1989;

O'Keane et al., 1992; Siever & Trestman, 1993). Studies of cerebrospi-

nal fiuid have shown that a decrease in 5-hydroxyindolacetic acid, a me-

tabolite of serotonin (5-HT), is associated with impulsive aggression in

patients with BPD, as well as in depressed patients, volunteers, and vio-

lent alcoholic offenders (Linnoila et al., 1989; Linnoila et al., 1994;

Viikkunen et al., 1994). Peripheral measures of 5-HT activity, includ-

BORDERLINE PERSONALITY DISORDER

FIGURE 1

Brain Systems in Borderline Personality

Dimension

Disorder

Neuroanatomic

Circuitry

Orbitai frontal cortex /

Anterior cingulate

cortex/Amygdala

Neuromoduiator

Impulsivity/Aggression

Serotonin

Affective Instability

Amygdala /

Enterorhinal Cortex

Acethycholine,

norepinephrine

Cognitive

Disorganization

Prefrontal cortex/

Striatum

Dopamine

ing platelet 5-HT levels and paroxetine binding, measures believed to

refiect central nervous system serotonin activity, are similarly de-

creased in impulsive aggression (Verkes etal., 1998; Mann etal., 1992).

Neuroendocrine challenge studies have played a key role in linking

5-HT hypofunction to the pathophysiology of impulsive aggression.

Such studies measure receptor-mediated neurohormonal responses to an

agent that normally triggers the secretion of 5-HT, thereby providing data

on system responsivity. The earliest challenge studies measured plasma

levels of prolactin (a hormone released frotn the anterior pituitary in re-

sponse to 5-HT stimulation), after administration of a 5-HT agonist, usu-

ally d-fenfiuramine, and found the response to be blunted in personality

disordered patients with impulsive aggression(Coccaro et al., 1996;

Siever et al., 1993; New et al., 2004a; Soloff et al., 2003a), and socio-

pathy (O'Keane et al., 1992). More recent challenge studies using meta-

chlorophenyl-piperazine (m-CPP) have shown similar findings (Paris et

al., 2004; New et al., 2002). Cumulatively, these results have suggested

that the neuroendocrine response is related to dimensional measures of

itnpulsive aggression rather than to the BPD diagnosis per se.

Goodman, Triebwasser. and New

Neuroimaging Studies and Circuitry

Although the 5-HT system has been implicated in the etiology of im-

pulsive aggression, the exact nature of the dysfunction and the identities

of the brain systems involved remain elusive. Likely brain regions in-

clude the orbital frontal cortex (OFC), which inhibits limbic and other

subcortical regions and is part of the prefrontal cortex (PFC), the area in

the brain that controls "higher" functions involving cognition, planning

and the processing of memories and feelings. Other implicated brain re-

gions are the anterior cingulate cortex (ACC), which assesses affective

incoming stimuli critical to the initiation of aggtession, and the adjacent

ventral medial cortex (VMC). New et al. (2002) assessed 5-HT activity

in several brain regions by comparing changes in regional glucose rne-

tabolism after m-CPP versus placebo in 13 impulsive aggressive pa-

tients and 13 age- and gender-matched controls. Impulsive aggressive

patients, compared to normals, demonstrated decreased activation of

inhibitory regions in the left anteromedial OFC. Moreover, patients

but not controls showed deactivation of the ACC and instead showed

activation of the posterior cingulate gyrus. These findings demonstrate

differing patterns of brain activation in impulsive aggressive personal-

ity disordered subjects compared to controls.

Supporting this conclusion are other PET studies in impulsive ag-

gressive and/or BPD subjects that have demonstrated blutited responses

in the OFC, adjacent VMC, cingulate cortex (Siever et al., 1999;

Schmahl et al., 2003; Soloff et al., 2003b) and dorsolateral prefrontal

cortex (DLPFC) (Schmahl et al., 2003), and hypometabolism in the hip-

pocampus and cuneus regions (Juengling et al., 2003). These important

findings suggest that specific brain structures, including the ACC and

areas of the frontal cortex, all of which are involved in 5-HT function,

are implicated in impulsive aggression.

Turning to the relatively new field of molecular neurotransmitter

studies, our understanding at the microscopic level of the serotonergic

disturbances associated with impulsive aggression has yet to be worked

out fully. Nevertheless, the scientific community knows much more

now than it did even a few years ago, largely because of a relatively re-

cent advance in PET scanning-the availability of radioactive "ligands"

that bind to specific proteins that line nerve cell surfaces within the

5-HT system.

The proteins of greatest interest are the various "receptors," to which

the 5-HT molecule binds and which then initiate its physiological ef-

fects and the "transporters," which scoop up and inactivate the neuro-

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