The Biology of Borderline
Personality Disorder
by Larry J. Siever,
M.D.
Borderline Personality
Disorder (BPD) is a diagnosis that has many different meanings
depending on the tradition or discipline from which it is viewed.
In this sense, the disorder is somewhat like the elephant in the
parable of the blind man and the elephant. Psychoanalytically
oriented practitioners focus on its intrapsychic structures and
defense mechanisms such as "splitting," while interpersonally
oriented clinicians understand the borderline in terms of
disturbances in their interpersonal relatedness.
Psychopharmacologists tend to understand borderline patients in
terms of atypical affective disorders, or impulse related
disorders and treat according to these target symptom
areas.
The two hallmark
psychobiologic vulnerabilities or temperamental predispositions
are affective instability and impulse aggression.
The individual with BPD is exquisitely affectively sensitive
to environmental shifts, particularly in their interpersonal
sphere, so that they react with feelings of, for example, rage and
despair and separation, humiliation and fury at a setback at work,
etc. It is likely that this highly sensitive affective thermostat
is present from a very early age and may apparently have genetic
as well as early environmental antecedents. This affective
sensitivity during the course of early development may prove a
challenge to the successful mastery of the developmental tasks of
childhood and adolescence. For example, an infant who is very
sensitive to separation or bodily pain may cry more frequently and
be more difficult to soothe when mother or other caretaker leaves,
the baby may cry loudly and persistently. For a depressed or
affectively sensitive parent, such a child can present a
particularly formidable challenge. As the child grows older, these
crying spells may turn into temper tantrums. For even the most
empathic parent, there may be a temptation to respond to these
tantrums with either excessive indulgence or at other times
inattention of neglect. For the child, these inconsistent
responses may constitute a sort of "intermittent reinforcement"
making their temper tantrums more likely. The temper tantrums may
be the antecedents to affective storms that we may see in
the borderline patient during adulthood when threatened with a
potential loss of a relationship or feelings of
abandonment.
There are some suggestions
that there may be biologic underpinnings to this affective
sensitivity or instability. Patients with BPD tend to show greater
responses to pharmacologic agents that may induce affective
changes. For example, work in our laboratory has suggested
that borderline patients with affective instability respond to
administration of physostigmine, a cholinesterase inhibitor that
prevents the breakdown of acetylcholine, with marked feelings of
negative mood or dysphoria. This response was not observed in
patients with other personality disorders or a normal volunteer
comparison group. This dysphoric response parallels that seen in
depressed patients, both when acutely ill or intermittent,
suggesting that the cholinergic system may play a role in
mediating the dysphoric affects of borderline personality disorder
patients. Interestingly, the degree of dysphoric responses are
correlated with affective instability and related traits at
baseline, but not with other criteria for borderline personality
disorders that reflect impulsivity and aggression.
Impulsive aggression is also
a core feature of BPD. The borderline patients engage in self
damaging acts, including self mutilating behavior and suicide
attempts, particularly when frustrated or disappointed. These may
be considered as instances of self directed aggression. They also
are prone to angry outbursts that interfere with the stability of
their relationships. They are impulsive, reflected in behavior
such as binge eating, gambling, substance abuse, promiscuity, or
reckless driving.
The borderline personality
disordered individual appears to have a lower threshold to
environmental stimuli, particularly frustrating stimuli, resulting
in disinhibited impulsive aggressive behaviors. In addition, their
propensity towards self directed aggression is also greater. Their
personality may in part be organized around these aggressive
outbursts or traits and intimacy becomes difficult because of
their chronic irritability and anger. Their motor disinhibition is
associated with a difficulty in mastering aggression and
effectively separating or individuating from others they depend on
during the course of their development.
There is good evidence that
the tendency to impulsive aggression has psychobiologic
substrates. The serotonin system is a behavioral suppressive
system that is involved in modulation of appetite, mood,
temperature regulation, and a variety of vegetative functions.
Serotonergic neuronal activities increase during repetitive self
directed behaviors and may decrease when an organism attends to
novel events in their environment. Lesions of serotonergic
neurons, result in disinhibited aggression, for example, in rats -
the killing of mice placed in their vicinity. Furthermore, rats
with lesions of the serotonergic system cannot learn to extinguish
or dampen bar pressing behavior in paradigms where the bar
pressing was previously rewarded and is currently punished. In
other words, these animals appear to have a deficit in the
suppression of punished behaviors.
In humans, reductions in
serotonergic activity are associated with impulsive aggressive
behavior. Neuroendocrine responses to the serotonin releasing
agent fenfluramine are blunted, suggesting reduced serotonergic
activity in patients with BPD. They are specifically associated
with those criteria of BPD that reflect impulsive aggressive
traits that reflect impulsive aggressive traits such as angry
outbursts, impulsivity, and self-damaging acts. They are not
associated with interpersonal or affective related traits,
however. Indeed, the prolactin response to fenfluramine is highly
inversely associated with self ratings of irritability and
assaultiveness, with the greatest reductions in serotonergic
activity being associated with the highest reported
irritability and aggression. Thus, the association between reduced
serotonergic activity and aggression does not seem specific to
BPD, but rather to impulsivity and aggression which may be found
in other personality disorders such as antisocial personality
disorder as well. In fact, studies of antisocial personality
disorder patients also reported blunted prolactin responses to
fenfluramine.
Genetic studies of
monozygotic and dizygotic twins suggest that there may be genetic
factors for these dimensions of emotional reactivity and impulsive
aggression, while there does not appear to be a heritability for
BPD as a category. Family members of BPD patients are more likely
to demonstrate affective instability or impulsivity, although not
necessarily both. Impulsivity and aggression seem to be heritable
in studies of normal twins as well. It is noteworthy that in the
studies of prolactin responses to fenfluramine, blunted prolactin
response to fenfluramine in a patient is a better predictor of
impulsivity and aggression in their relatives than was impulsive
aggression as a behavior in itself in the patient. These results
would suggest that what is inherited is not the behavior, but an
alteration in the serotonergic system that may at times be
expressed in a propensity to impulsive
aggression.
It is also clear that the
environment plays an important role in the development of
borderline personality disorder and may even influence the biology
of impulse and affect regulation. One prominent environmental
antecedent to BPD is a history of abuse or neglect. Many studies
suggest a high proportion of borderline patients have experienced
some form of abuse, particularly sexual abuse, during their
development. While it is not clear that BPD over other personality
disorders always have a demonstrated increased history of abuse,
there is no doubt that the history of abuse is common in
personality disorder patients, particularly in BPD
patients.
New studies suggest that
abuse may sensitize or alter the activity of the stress system
such as the hypothalamopituitary-adrenal (HPA) axis and may have
long term effects on the monoamine systems as well. Some studies
even suggest that certain kinds of trauma or early abuse may
actually cause structural changes in a central part of the brain
involved in emotional memories, the hippocampus. Thus, we are just
beginning to understand the biologic sequelae of early events of
abuse.
While we are only beginning
to understand the biologic aspects of BPD, it is clear that the
development of BPD depends on an interaction of constitutional
biologic vulnerabilities with often adverse environmental
circumstances during development. However, we are only beginning
to understand the mechanism by which these events happen.
Hopefully, a more thorough understanding of the psychobiology of
this disorder may promote improved treatment, both
psychopharmacologically, and psychotherapeutically in an
interpersonal content.
Courtesy of Larry J. Siever,
M.D.
The Journal of the California Alliance for the Mentally
Ill
1997
Dr. Siever is the author of
The New
Psychiatry; How Genes and Neurotransmitters Shape Your Mind,
Personality, and Mental Health
Dr. Siever is the Director
of the Outpatient Psychiatric Division of Bronx, V.A. Medical
Center and Professor of Psychiatry at Mount Sinai
School of Medicine.
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