Previous work by the group convinced the researchers to pursue development of focused cognitive reappraisal training as a novel approach to treatment of BPD, either as stand-alone treatment or in concert with evidence-based treatments of BPD. The present proposal aims to refine and test a proposed clinical intervention for BPD patients, training in reappraisal-by-distancing, in terms of its ability to influence hypothesized neural and behavioral targets and, once that is established, to demonstrate its ability improve clinically relevant outcome measures.

Borderline Personality Disorder (BPD) is a prevalent, enduring and disabling psychiatric condition found in approximately 2% to 5.9% of the population and 20% of hospitalized psychiatric patients. Suicide rates of approximately 10% have been reported. One of the most prominent clinical features of BPD is extreme mood shifts occurring in response to external social/emotional events. The emotional instability in BPD contributes to many of the most disabling, even life-threatening, symptoms of the disorder, including suicidality, outbursts of intense anger, and seriously impaired role functioning. The severity of the BPD symptom profile, its prevalence, chronicity and high burden upon health care services make the development of effective and accessible treatment for BPD a high priority. Yet there is no current medication treatment indicated for BPD and the psychotherapies recognized for the disorder have been shown to have small effect sizes and are of limited availability. The present study builds upon work by the group that has shown that deficiencies in the ability to regulate emotion by engaging typically adaptive cognitive strategies (cognitive reappraisal, CR) and to effectively activate associated neural systems can be corrected by focused training in CR. The R61 phase of this study examines a manualized intensive training program in CR, tests that it effects target neural systems implicated in emotional processing and enhances behavioral reappraisal success. It examines 2-, 4- and 6- weeks of twice a week treatment to identify the optimal dose. Measures include fMRI imaging and clinical ratings at baseline and each of these subsequent time points. Upon demonstrating that CR training is superior to a control condition in enhancing performance in the neural target at one or more of these dose durations, the researchers will proceed to the R33 phase. In the R33 phase, the researchers will treat a larger sample of BPD patients at the optimal 6-week dose defined in the R61 phase to 1) demonstrate reproducibility of the R61 findings, 2) to demonstrate that CR training is superior to control in improving BPD clinical outcomes at the end of treatment and at 1- and 4- month follow-up, and 3) that change in activity at the neural targets is associated with clinical improvement. The results of this study can support the introduction of CR training as a new psychosocial approach for the treatment of BPD, either as stand-alone treatment or as an augmenting strategy. It may, moreover, have application to a range of psychiatric disorders characterized by severe emotional instability.

Inclusion Criteria:

• Medically healthy men and women with Borderline Personality Disorder who are mentally competent and give informed voluntary written consent.
• Participants will be between the ages of 18 and 55.
• Within these requirements, the inclusion and exclusion criteria do not reflect participation based on gender or racial/ethnic group. The targeted/planned enrollment is a reflection of previous recruitment of female and ethnic minorities in other studies conducted by the PI and their colleagues and includes representations of both genders and all minorities.
• Participants with comorbid avoidant personality disorder will be included.
• Participants who meet criteria for PTSD will be included as long as they are not actively experiencing symptoms.

Exclusion Criteria:

• Participants will not meet criteria for Schizotypal Personality Disorder.
• Participants currently meeting criteria for Major Depressive Disorder will be excluded.
• BPD participants will not meet DSM-5 criteria for present PTSD, bipolar I disorder, schizophrenia, schizoaffective disorder, substance use disorder within the past 6 months, organic mental syndromes, head trauma, schizotypal personality disorder, avoidant personality disorder, CNS neurological disease, or seizure disorder. Participants meeting criteria for a non-IV substance use disorder more than 6 months prior to enrollment will not be excluded. This study allows patients who are currently taking psychotropic medications or are in psychotherapy, so long as there has been no change in medication or psychotherapy over the preceding two months.
• Participants currently meeting criteria for major depressive disorder.
• Participants meeting criteria for substance use disorder within the last 6 months or of an IV-substance use disorder at any time.
• Participants may not have a pacemaker, surgical clips, any metallic implants, or shrapnel fragments that would contraindicate MRI scanning.
• Pregnant women.

Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).

Beginning 9 months and ending 36 months following article publication.

Investigators whose proposed use of the data has been approved by an independent review committee ('learned intermediary') identified for this purpose.

For individual participant data meta-analysis.