PROJECT SUMMARY/ABSTRACT
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.