BPD is a serious and costly public health problem. To develop effective preventative and early interventions for BPD as symptoms emerge across adolescence, it is crucial to understand the biological and behavioral mechanisms via which a subset of adolescents vulnerable to negative emotions also develop the relational and behavioral dysregulation that makes BPD so challenging to treat. Rumination on anger may amplify anger as a preferred state to shame and feelings of rejection, while contributing to the dysregulation typical of BPD. Unlike other negative emotions, anger increases both arousal and approach motivation. Accordingly, AR may not only dampen BPD individuals? self-directed negative affect (negative reinforcement), but also provide them with feelings of validation, empowerment, and pleasure (positive reinforcement). This theory suggests a potential neural mechanism contributing to BPD development: sensitization of the dopaminergic reward system localized within the nucleus accumbens (NAcc) to repeated engagement in AR. The proposed study?s central hypothesis is that repeated use of AR as an emotion regulation strategy to manage the pain of rejection is immediately rewarding, but with the cost of increased risk of the wide range of dysfunctional, impulsive behaviors characteristic of BPD. The neural circuitry of rejection and AR will be examined in a non-clinical sample of adolescent girls (N=60) aged 13-16, with heightened emotional vulnerability and endorsing a range of AR. To examine AR-related NAcc recruitment, following assessments, participants will engage in fMRI- monitored paradigms involving interpersonal rejection, and subsequent prompts to engage in angry, depressive, positive and neutral thought. Neural correlates of AR will be used to predict BPD features and related outcomes at 6 and 12 months, as well as networks modeling the interplay among BPD features, including links between internalized negative affect and dysregulated behavior. The training plan closely matches the proposed research and long-term goals with an emphasis on activities that will facilitate the candidate?s development as an independent investigator. Specifically, the training aims are to: (1) Gain experience in translational research with adolescents, including ethical issues with this protected population; (2) Acquire the theoretical and methodological skills required for designing, implementing, and analyzing data from fMRI studies; (3) Learn network analysis and apply these skills to the assessment of psychopathology. A mentorship team with expertise across these areas has been assembled, and Brown University is a world- renowned clinical research institution with an extensive history of NIH funding and supporting career development awards. Overall, the broad aim of these research and training goals is to support the candidate?s development of an independent research program examining maladaptive anger regulation as a potential biologically-based intervention target in the development of BPD and other forms of psychopathology.

Public Health Relevance

Understanding mechanisms underlying the development of BPD features in adolescence is critical to developing effective interventions for this challenging and expensive to treat disorder. The proposed research tests a theory that anger rumination functions as a directly rewarding but maladaptive emotion regulation strategy that confers risk on a neurological level for the development of the reactive, impulsive, and aggressive habits characteristic of BPD. Specifically, the impact of anger rumination on neural reward circuits will be assessed, and this reward activation used to predict connections between internalizing and impulsive networks of BPD symptoms.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23MH112889-03
Application #
9914134
Study Section
Child Psychopathology and Developmental Disabilities Study Section (CPDD)
Program Officer
Bechtholt, Anita J
Project Start
2018-04-01
Project End
2023-03-31
Budget Start
2020-04-01
Budget End
2021-03-31
Support Year
3
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Brown University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
001785542
City
Providence
State
RI
Country
United States
Zip Code
02912
Peters, Jessica R; Eisenlohr-Moul, Tory A; Walsh, Erin C et al. (2018) Exploring the pathophysiology of emotion-based impulsivity: The roles of the sympathetic nervous system and hostile reactivity. Psychiatry Res 267:368-375