Neural Mechanisms Underlying Self-Critical Rumination and Self-Reassurance and Suicidal Thoughts and Behavior in Youth

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Suicide is the second leading cause of death among 10-34 year-olds. Aligning with the NIMH's Prioritized Agenda for Suicide Prevention Research, this K23 career development award seeks to advance what is known about the brain/behavior mechanisms underlying self-critical rumination ─ defined as persistent negative-self- evaluation ─ and self-reassurance ─ providing compassion to self. This K23's central hypothesis is that circuit alterations in the dorsolateral and dorsomedial prefrontal cortex, dorsal anterior cingulate, and insula underlying self-critical rumination and self-reassurance is associated with increased suicidal thoughts and behavior (STB) in adolescents. Our central methodology is to examine self-critical rumination and self- reassurance using task-dependent and task-independent functional magnetic resonance imaging (fMRI) and ecological momentary assessment (EMA) in 90 12-15 year-old girls recruited on the range of STB. This age group represents a critical developmental period for these self-referential processes and youth in this age- group experienced a sharp increase in suicide rates over the last decade. Our focus on only girls is due to greater prevalence of self-criticism among females compared to males, but we plan to examine potential sex- differences in future studies. This K23's research goals are to: (i) test the associations between in vivo self- critical rumination, self-reassurance, and STB; (ii) identify neural mechanisms underlying self-critical rumination and self-reassurance; (iii) integrate the findings from the scanner with STB assessed in adolescents' real world environment. This K23's career development goals are to gain hands-on mentorship with (i) task-dependent and task-independent fMRI to assess circuit function; (ii) EMA for better real-world assessment of self-critical rumination and self-reassurance; (iii) statistical approaches for imaging and EMA data; (iv) professional development and collaboration skills. This K23 is significant, because identifying specific neural mechanisms underlying the interplay between self-critical rumination, self-reassurance, and STB can help ascertain which teens are at a greater risk for STB and contribute to development of novel, mechanistically-informed interventions. This study, combined with the completion of proposed training goals, will effectively propel the candidate towards establishing an independent program of research focused on identifying bio-behavioral mechanisms and developing preventative interventions for youth suicide risk. This K23 is innovative because this will be the first project to identify specific neural mechanisms of self-critical rumination and self- reassurance in adolescents focusing on: (i) identifying construct-specific neural mechanisms; (ii) a trans- diagnostic sample of teenagers selected on the range of STB; (iii) integration of imaging and EMA techniques. The proposed mentors (Drs. Dickstein, Armey, Jones, and Brick) and consultants (Drs. Price and Maratos) have extensive experience to support the proposed training goals. The Department of Psychiatry and Human Behavior at Brown University is an outstanding environment for the proposed training and research.