Ovarian Hormone Withdrawal and Suicide Risk: An Experimental Approach

项目摘要/摘要 总统、卫生局局长和NIMH赞助的自杀研究优先顺序最近的呼吁 议程强调迫切需要确定急性自杀风险的生物学预测因素，这些因素包括 易于干预的。作为回应，拟议的实验工作调查了 围绝经期(月经前后)停用雌激素(E2)和孕酮(P4) 先前记录的围绝经期自杀率急剧上升。拟议的项目也充分 为候选人在自杀病理生理学方面具有独特影响力的研究生涯做好准备。的目的是 建议的K99研究是为了检验这样一种假设，即自然的围绝经期E2/P4剧烈地退出 会增加自杀倾向。采用安慰剂对照的人内设计，对30名患有目前 自杀意念但自杀企图的风险很小，这项实验将检验自杀将 在自然围绝经期E2/P4停药期间(在安慰剂下)升高，但实验 防止围绝经期E2/P4停药将防止围绝经期自杀率增加。这个 R00研究的目的将是解开E2和P4停药在围绝经期恶化中的作用。 使用扩展的三臂人内试验自杀(围绝经期E2/P4戒断) 安慰剂，E2稳定[围绝经期P4停药]，P4稳定[围绝经期E2] 同样在30名目前有自杀意念但自杀未遂风险最低的女性中。据预测， 只有自然的P4戒断情况才会与自杀恶化有关，这是由戒断引起的 来自P4衍生的神经类固醇。这两个项目都将使用多模式测量(任务、访谈、电话 评估和生态瞬时评估[EMA])。导师：来自北卡罗来纳大学教堂山分校和 邻近的杜克大学将指导候选人：苏珊·格德勒博士(导师)将提供指导 在荷尔蒙操纵方面。米奇·普林斯坦博士(共同导师)将提供自杀和风险方面的指导 管理层。David Rubinow医学博士在卵巢激素的神经生物学效应方面贡献了专业知识。 史蒂文·杨，医学博士，博士，在月经周期的操纵方面贡献了专业知识。丹尼尔·鲍尔，博士。 提供高级统计方面的专业知识。M.Zachary Rosenthal博士贡献了自杀方面的专业知识和 埃玛。职业目标：应聘者致力于研究荷尔蒙变化的作用 在冲动和自杀方面。她的目标是通过R01资助的项目贡献知识，同时 将发现转化为治疗方法。职业发展：她之前的工作确立了她的未来 急性荷尔蒙变化与冲动(攻击性、酗酒)之间的联系；该奖项将 允许她培养进行安全实验的技能，这些实验将确定激素变化的因果作用 有自杀倾向。培训结果包括荷尔蒙实验技能、基于研究的自杀风险 自杀相关概念的管理、生态瞬时评估和多模式测量。

PROJECT SUMMARY/ABSTRACT Recent calls from the President, Surgeon General, and the NIMH-sponsored Suicide Research Prioritization Agenda emphasize a dire need for the identification of biological predictors of acute suicide risk that are amenable to intervention. In response, the proposed experimental work investigates a causal role of perimenstrual (around menses) withdrawal from the hormones estradiol (E2) and progesterone (P4) in previously-documented acute perimenstrual increases in suicidality. The proposed project also fully prepares the candidate for a uniquely impactful research career in the pathophysiology of suicide. The aim of the proposed K99 research is to test the hypothesis that natural perimenstrual E2/P4 withdrawal acutely increases suicidality. Using a placebo-controlled, within-person design in a sample of 30 women with current suicidal ideation but minimal risk for suicide attempt, the experiment will test the hypothesis that suicidality will be heightened during natural perimenstrual E2/P4 withdrawal (under placebo), but that experimental prevention of this perimenstrual E2/P4 withdrawal will prevent these perimenstrual increases in suicidality. The aim of the R00 research will be to disentangle the roles of E2 and P4 withdrawal in perimenstrual worsening of suicidality using an expanded three-arm within-person experiment (perimenstrual E2/P4 withdrawal under placebo, E2 stabilization [with perimenstrual P4 withdrawal], and P4 stabilization [with perimenstrual E2 withdrawal]), also in 30 women with current suicidal ideation but minimal suicide attempt risk. It is predicted that only natural P4 withdrawal conditions will be associated with worsened suicidality, mediated by withdrawal from P4-derived neurosteroids. Both projects will utilize multi-modal measurement (tasks, interviews, phone assessments, and ecological momentary assessment [EMA]). Mentorship: Experts from UNC Chapel Hill and neighboring Duke University will mentor the candidate: Susan Girdler, Ph.D. (mentor) will provide mentorship in hormone manipulation. Mitch Prinstein, Ph.D. (co-mentor) will provide mentorship in suicide and risk management. David Rubinow, M.D. contributes expertise in the neurobiological effects of ovarian hormones. Steven Young, M.D., Ph.D. contributes expertise in manipulation of the menstrual cycle. Daniel Bauer, Ph.D. provides expertise in advanced statistics. M. Zachary Rosenthal, Ph.D. contributes expertise in suicidality and EMA. Career Goal: The candidate is committed to a research career focused on the role of hormone changes in impulsivity and suicidality. Her goal is to contribute knowledge through R01-funded projects while also translating findings into treatments. Career Development: Her previous work has established prospective associations between acute hormone changes and impulsivity (aggression, alcohol abuse); this award will allow her to develop skills to conduct safe experiments that will determine the causal role of hormone change in suicidality. Training Outcomes include skills in hormonal experiments, research-based suicide risk management, ecological momentary assessment, and multimodal measurement of suicide-related constructs.