Treatment of Aggression, Anger and Emotional Dysregulation in Borderline Personality Disorder

Borderline Personality Disorder (BPD) is a disabling disorder characterized by poor affect
regulation and poor impulse control. This often results in impaired interpersonal
relationships and maladaptive behavioral patterns, including anger dyscontrol, aggression
towards others and self-destructive behaviors. Evidence suggests that is a relatively common
disorder, affecting 2% of the population 1. In addition, BPD patients have more frequent
psychiatric hospitalizations, greater use of outpatient psychotherapy and more visits to the
emergency room than individuals with any other psychiatric disorder 3, 4. Due to the
heterogeneity of symptoms that fall under the DSM-IV definition of BPD, the most productive
efforts to understand the underlying neurobiology of this disorder have employed a
dimensional approach. This application focuses on the domain of affective instability and
altered emotion regulation, believed by many to be at the core of the disorder 5.

The emotional dysregulation of BPD appears to be a biological vulnerability. This
vulnerability includes both increased emotional reactivity, as well as an impaired capacity
to employ effortful control in the modulation of emotional reactions. The emotional
reactivity is manifested by high sensitivity to emotional stimuli and heightened emotional
intensity5 and may reflect limbic system over activity. The impairment in emotional
modulation results in a slow return to the baseline emotional state and may reflect deficits
in prefrontal regulatory regions. While data supporting this formulation are limited,
self-report measures of responses to various emotional stimuli and more recently, objective,
non-verbal physiological measures including startle eye blink modulation (SEM), have been
used to test this theory.

SEM is a well-established technique used to study the psychophysiology of emotion and has
been shown to reflect amygdala activation6. Our research group has demonstrated exaggerated
affective startle in BPD patients compared to healthy control subjects at later probe
positions in response to words with emotionally negative valence, selected specifically to
target emotions commonly unpleasant for BPD patients. Emerging neurobiological theories
based on preliminary functional neuroimaging studies posit that BPD is a
hyperarousal-dyscontrol syndrome 4, implicating dysfunction in amygdala activity coupled
with weakening of prefrontal inhibitory control. Several neuroimaging studies from our
research group have helped advance this idea7. Building on these exciting findings and the
expertise available, this project uses a translational approach to study treatment effects
on emotional regulation in BPD with SEM and prediction of treatment response with functional
magnetic resonance imaging (fMRI).

Dialectical Behavior Therapy is an empirically validated treatment approach emphasizing the
role of emotion regulation in the treatment of suicidal and self-destructive behaviors in
BPD8, 9. It has gained considerable popularity and is included as a component of the APA
guidelines for treatment of BPD10. While this approach stresses skills and techniques for
emotional regulation, and encourages cognitive control over maladaptive behavioral patterns,
there have been neither neuroimaging nor psychophysiological studies of the effect of DBT on
emotional processing in BPD, despite its proven efficacy. While neuroimaging and
psychophysiological studies of a psychotherapeutic treatment have been done in major
depression 11, 12 13, no such studies have been done in BPD. By examining changes in
affective startle and baseline predictors of response with fMRI blood oxygenation level
dependent (BOLD) activation patterns associated with DBT treatment, this project aims to
better characterize the nature of emotional dysregulation in BPD, and identify features that
predict a good response to DBT treatment. In addition, the project will explore the
relationship between clinical improvement of BPD symptomatology with DBT treatment and
changes in neurobiological measures by performing follow-up SEM after six and twelve months
of DBT treatment. This approach will help elucidate the neuroanatomy of abnormal emotional
processing in BPD and may help identify potential strategies for correcting these deficits.

Inclusion Criteria:

- Able to provide written informed consent

- In good physical health as confirmed by a complete physical exam, electrocardiogram,
neurological exam, and routine laboratory tests of blood and urine

- A negative urine toxicology screen

- Completion of psychiatric evaluations, medical evaluations, and self-report
questionnaires through separate protocol- Biological Correlates of Personality
Disorders (GCO #88-244)

1. meet DSM-IV criteria for borderline personality disorder and have an overt
aggression scale- modified aggression subscale score of six or above on one of
two OASM pre-treatment screens.

2. not currently be taking any psychiatric medications. If they have taken
psychiatric medications in the past, they must be at least 2 weeks (6
half-lives) medication-free prior to participating in the study. These
medications include mood stabilizers, antidepressants, antipsychotics, and
benzodiazepines.

Exclusion Criteria:

- meet criteria for schizophrenia, bipolar I disorder, schizoaffective disorder or any
other psychotic disorder.

- have met criteria for substance abuse or dependence during the 6 months prior to
entry into the study

- have a past history of intravenous drug use, cocaine abuse or dependence, or any
substance dependence that resulted in serious medical sequelae

- meet criteria for current MDE, as they may require antidepressant treatment

- have made a suicide attempt or had a psychiatric hospitalization during the 6 months
prior to entry into the study

- be on any psychotropic medication(s) upon entry into the study

- be in concurrent psychotherapy (case management services and work therapy programs
are not considered individual psychotherapy)

- be pregnant or lactating