Neural Mechanisms and Predictors of an Ultra-Brief Suicide Prevention Strategy

每年有近45000名美国人死于自杀，在过去的两年里，自杀人数一直在稳步上升 几十年。迫切需要更好地获得有效的自杀预防战略，这些战略是高度 可跨医疗环境运输。来自当前团队的数据表明，危机的一次会议 反应计划(CRP)减少了76%的自杀行为；然而，目前还不清楚CRP是如何工作的，并且对于 谁，削减战略优化和广泛实施。临床医生推测，CRP的作用机制是 增强情绪调节能力和降低应激反应；然而，这一假说从未 已经过测试，先前没有研究确定自杀风险变化的神经机制和预测因素 在干预之后。相关的，没有客观的基于大脑的标记物来说明自杀风险的降低 临床决策，引导高危患者到所需服务。为了弥补这些差距，并最终 改善自杀预防工作我们寻求确定基于大脑的机制和变化的预测因素 在一组有积极自杀意向的成年人中，一次C反应蛋白治疗后的自杀倾向。我们将采取一项 探索应激反应和情绪调节神经回路的创新和综合方法 临床试验设计的背景。具体地说，我们将结合信息来源，同时 收集神经功能、心理生理学(即惊吓眨眼增强)、行为的评估 和在功能磁共振成像(FMRI)前(时间1)和之后(时间2)的自我报告 随机进行一次一小时的C反应蛋白治疗或标准自杀风险管理(对照)。一小块 一组没有自杀意念或意图的志愿者将被包括在内，以供比较。利用生态 瞬时评估(EMA)技术，将评估干预后自杀倾向的急性变化 第一周每天两次。还将进行每月在线临床调查，并在6个月后- 在采取干预措施后，将重新管理整个多模式评估单元(时间3)。这一创新的， 多层纵向设计将允许很好地控制测试单次CRP如何敏锐地 改变自杀风险(目标1)。这项研究还将探讨C反应蛋白的急性影响是否持续 时间和神经功能如何影响自杀倾向的长期变化(目标2)。最后，我们将进行 复杂的分析以跨分析单元和功能域集成数据，以测试是否存在 是CRP介入治疗成功的可靠预后指标(目标3)。这项研究的结果将提供 关于CRP超简短会议如何工作以及为谁工作的关键新知识，同时揭示 自杀风险降低的机械信号。此外，与NIMH大脑计划的使命一致， 该奖项将促进国际和平协会创新翻译研究计划的启动，并为 一系列旨在确定解决自杀风险和检测的神经生物学目标的大规模研究 有效目标参与的干预措施是否能提高自杀预防效果。

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 innovative translational program of research and pave the way for a series of large-scale studies aimed at identifying neurobiological targets for resolving suicide risk and testing whether interventions with effective target engagement can enhance suicide prevention outcomes.