Ovarian Hormone Withdrawal and Suicide Risk: An Experimental Approach

卵巢激素撤退和自杀风险：实验方法

• 批准号: 9243486
• 负责人: Tory Anne Eisenlohr-Moul
• 金额: $ 8.2万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-14 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9243486
• 关键词: Acute; Aggressive behavior; Alcohol abuse; Allopregnanolone; Anxiety; Award; Behavior Therapy; Behavioral; Behavioral Symptoms; Biological; Clinical; Cognitive; Data; Doctor of Medicine; Doctor of Philosophy; Ecological momentary assessment; Estradiol; Feeling hopeless; Feeling suicidal; Female; Figs - dietary; Functional disorder; Funding; Goals; Hormonal; Hormones; Impulsivity; Intervention; Interview; Knowledge; Left; Link; Luteal Phase; Measurement; Measures; Mediating; Mediation; Menstrual cycle; Menstruation; Mental Depression; Mentors; Mentorship; Methods; Modeling; National Institute of Mental Health; Neurobiology; Outcome; Outpatients; Ovarian; Ovarian Steroid Hormone; Ovarian hormone; Pathway interactions; Persons; Phase; Physiological; Placebo Control; Placebos; Prevention; Process; Progesterone; Protocols documentation; Psychopathology; Public Health; Randomized; Readiness; Reporting; Research; Research Training; Rewards; Risk; Risk Assessment; Risk Factors; Risk Management; Role; Sampling; Side; Steroids; Stimulus; Suicide; Suicide attempt; Suicide prevention; Surgeon; Symptoms; Task Performances; Testing; Training; Translating; Universities; Withdrawal; Woman; Work; arm; base; behavioral construct; career; career development; clinical risk; cognitive control; design; emotional symptom; men; minimal risk; neurosteroids; perimenstrual; phase 1 study; phase 2 study; prevent; prospective; research study; response; skills; skills training; social; statistics; stem; suicidal; suicidal behavior; suicidal risk; suicidal women

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.

项目总结/摘要 最近来自总统，外科医生和NIMH赞助的自杀研究优先权的呼吁 议程强调迫切需要确定急性自杀风险的生物学预测因子， 易于干预。作为回应，拟议的实验工作调查的因果作用， 围月经期（月经前后）雌二醇（E2）和孕酮（P4）激素的戒断， 先前记录的急性围绝经期自杀倾向增加。该项目还全面 准备候选人在自杀的病理生理学独特的影响力的研究生涯。的目的 拟议的K99研究是为了检验这样一个假设，即自然的围月经期E2/P4急性戒断 增加自杀倾向。使用安慰剂对照，在30名妇女的样本中， 自杀意念，但自杀企图的风险很小，实验将测试自杀倾向将 在自然围绝经期E2/P4戒断期间（安慰剂下）， 预防这种围绝经期E2/P4的撤退将防止这些围绝经期自杀倾向的增加。的 R 00研究的目的将是解开E2和P4戒断在围绝经期恶化中的作用， 使用扩展的三臂人内实验（在 安慰剂、E2稳定[伴围绝经期P4停药]和P4稳定[伴围绝经期E2 退出]），也在30名妇女目前的自杀意念，但最小的自杀企图的风险。据预测 只有自然的P4戒断条件与自杀倾向恶化相关，由戒断介导 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 生态环境评估（Ecological Momentum Assessment）。导师：来自美国查佩尔山的专家， 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 荷尔蒙控制Mitch Prinstein博士（共同导师）将提供自杀和风险方面的指导 管理医学博士大卫·鲁比诺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·杨医学博士博士提供了操纵月经周期的专业知识。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， EMA.职业目标：候选人致力于研究职业生涯，专注于激素变化的作用 冲动和自杀倾向她的目标是通过R 01资助的项目贡献知识， 将发现转化为治疗。职业发展：她以前的工作已经建立了前景 急性激素变化和冲动（侵略，酗酒）之间的关联;这个奖项将 让她发展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， 自杀倾向培训成果包括激素实验技能，基于研究的自杀风险 管理，生态瞬时评估，以及自杀相关结构的多模式测量。