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

This study examines the effects of 12 months of dialectical behavior therapy (DBT) for subjects with borderline personality disorder on aggression, anger and emotional dysregulation. Treatment effects will be measured by changes in interview, self-report, psychophysiology testing and fMRI neuroimaging.

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.

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 BPD

The present study examines DBT treatment effect on emotion regulation in unmedicated outpatients with BPD as measured by changes in the Difficulties in Emotion Regulation Scale. The DERS is a brief, 36-item, self-report questionnaire. DERS total score ranges from 36- 180. Higher scores reflect higher difficulties in emotion regulation. The measure yields a total score as well as scores on six scales derived through factor analysis: 1. Nonacceptance of emotional responses, 2. Difficulties engaging in goal directed behavior, 3. Impulse control difficulties, 4. Lack of emotional awareness, 5. Limited access to emotion regulation strategies, 6. Lack of emotional clarity Responses are on a 5-point scale: 1=almost never, 2=sometimes, 3=about half the time, 4=most of the time, 5=almost always

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) 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. 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

Goodman M, Carpenter D, Tang CY, Goldstein KE, Avedon J, Fernandez N, Mascitelli KA, Blair NJ, New AS, Triebwasser J, Siever LJ, Hazlett EA. Dialectical behavior therapy alters emotion regulation and amygdala activity in patients with borderline personality disorder. J Psychiatr Res. 2014 Oct;57:108-16. doi: 10.1016/j.jpsychires.2014.06.020. Epub 2014 Jul 2.