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

每年有近4.5万美国人死于自杀，最近两年自杀率一直在稳步上升。 几十年迫切需要更好地获得有效的自杀预防策略， 可在医疗环境中移动。当前团队的数据表明， 反应计划（CRP）减少了76%的自杀行为;然而，CRP是如何工作的， 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，降低应激反应;然而，这一假设从未被证实。 之前的研究还没有确定神经机制和自杀风险变化的预测因素 干预后。相关的，没有客观的基于大脑的标记物来告知“降低”的自杀风险 临床决策和指导高风险患者所需的服务。为了弥补这些差距， 改善自杀预防工作，我们寻求确定大脑为基础的机制和变化的预测因素， 一组有主动自杀意图的成年人在单次CRP治疗后的自杀倾向。我们将采取一个 通过探索压力反应和情绪调节神经回路， 临床试验设计的背景。具体来说，我们将联合收割机的信息来源，同时 收集神经功能，心理生理学（即，惊吓眨眼增强），行为 在功能性磁共振成像（fMRI）之前（时间1）和之后（时间2）进行自我报告 随机分配到一个单一的，一个小时的CRP或标准自杀风险管理（对照）。一个小 一组没有自杀意念或意图的志愿者将被包括用于比较。运用生态 瞬时评估（EMA）技术，将评估干预后自杀倾向的急性变化 第一周每天两次每月还将进行在线临床调查，并在6个月后， 干预后，将重新进行整个多模式评估组合（时间3）。这一创新， 多层纵向设计将允许一个良好的控制测试如何一个单一的会议CRP急性 改变自杀风险（目标1）。该研究还将探讨CRP的急性效应是否持续超过 时间和神经功能如何影响自杀倾向的长期变化（目的2）。最后，我们将进行 复杂的分析，以整合跨“分析单元”和功能域的数据， 是CRP干预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的超简短会议如何工作以及为谁工作的关键新知识，同时揭示了 降低自杀风险的机械信号。此外，与NIMH脑计划的使命一致， 该奖项将促进PI的创新转化研究计划的启动，并为 一系列旨在确定解决自杀风险的神经生物学目标和测试的大规模研究 是否有效的目标参与干预可以提高自杀预防的结果。

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.