Close to 45,000 Americans die from suicide each year and rates have been steadily rising for the last two decades. There is an urgent need for better access to effective suicide prevention strategies that are highly transportable across medical settings. Data from the current team indicates that a single session of crisis response planning (CRP) reduces suicide behavior by 76%; however, it is unknown how CRP works, and for whom, curtailing strategy optimization and widespread implementation. Clinicians speculate that CRP works by strengthening emotion regulation capabilities and reducing stress reactivity; however, this hypothesis has never been tested and no prior study has identified neural mechanisms and predictors of changes in suicide risk following intervention. Related, there are no objective brain-based markers of ‘reduced’ suicide risk to inform clinical decision making and guide high-risk patients to needed services. To address these gaps and ultimately improve suicide prevention efforts we seek to identify brain-based mechanisms and predictors of changes in suicidality following a single session of CRP in a cohort of adults with active suicidal intent. We will take an innovative and comprehensive approach by probing stress reactivity and emotion regulation neural circuits in the context of a clinical trials design. Specifically, we will combine sources of information and simultaneously collect assessments of neural function, psychophysiology (i.e., startle eyeblink potentiation), behavior and self-report during functional magnetic resonance imaging (fMRI) before (Time 1) and after (Time 2) randomization to a single, one-hour session of CRP or standard suicide risk management (control). A small group of volunteers with no history of suicide ideation or intent will be included for comparison. Using ecological momentary assessment (EMA) technology, acute changes in suicidality following intervention will be assessed twice daily for the first week. Monthly online clinical surveys will also be administered, and at 6-months post- intervention, the entire multimodal assessment battery will be re-administered (Time 3). This innovative, multilayered, longitudinal design will allow for a well-controlled test of how a single session of CRP acutely changes suicide risk (Aim 1). The study will also address whether the acute effects of CRP are sustained over time and how neural function influences long-term changes in suicidality (Aim 2). Lastly, we will conduct sophisticated analyses to integrate data across ‘units of analysis’ and functional domains to test whether there are reliable prognostic indicators of CRP intervention success (Aim 3). Findings from this study will provide critical new knowledge regarding how an ultra-brief session of CRP works and for whom, while uncovering a mechanistic signal of reduced suicide risk. In addition, consistent with the mission of the NIMH BRAINS program, the award will facilitate the launch of the PI’s innov...