Ovarian Hormone Withdrawal and Suicide Risk: An Experimental Approach

卵巢激素撤退和自杀风险：实验方法

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/摘要最近来自总统、卫生局局长和 NIMH 资助的自杀研究优先项目的电话议程强调迫切需要确定急性自杀风险的生物预测因子，这些预测因子是易于干预。作为回应，拟议的实验工作调查了因果关系月经期间（月经前后）雌二醇 (E2) 和黄体酮 (P4) 激素的戒断先前有记录显示，经期前后自杀倾向急剧增加。拟议的项目也充分帮助候选人为自杀病理生理学领域具有独特影响力的研究生涯做好准备。的目的拟议的 K99 研究是为了检验以下假设：经期自然 E2/P4 戒断会急剧增加自杀倾向。在 30 名患有当前症状的女性样本中使用安慰剂对照的内部设计自杀意念但自杀企图的风险最小，该实验将检验自杀倾向的假设在自然经期 E2/P4 戒断期间（安慰剂下）会升高，但实验结果表明预防经期 E2/P4 戒断将防止经期自杀倾向的增加。这 R00 研究的目的是阐明 E2 和 P4 戒断在围经期恶化中的作用使用扩大的三臂人内实验（围经期 E2/P4 戒断实验）来了解自杀倾向安慰剂、E2 稳定 [伴有围经期 P4 撤药] 和 P4 稳定 [围经期 E2 戒断]），也在 30 名目前有自杀意念但自杀企图风险极小的女性中进行。据预测只有自然的 P4 戒断条件才会与戒断介导的自杀倾向恶化相关来自 P4 衍生的神经类固醇。这两个项目都将利用多模式测量（任务、访谈、电话评估和生态瞬时评估[EMA]）。指导：北卡罗来纳大学教堂山分校的专家和邻近的杜克大学将指导候选人：Susan Girdler 博士。（导师）将提供指导在激素操纵中。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。 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，博士贡献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.扎卡里·罗森塔尔博士贡献自杀方面的专业知识和 EMA。职业目标：候选人致力于从事激素变化作用的研究事业冲动和自杀倾向。她的目标是通过 R01 资助的项目贡献知识，同时也将发现转化为治疗方法。职业发展：她之前的工作已经建立了前景急性激素变化与冲动（攻击性、酗酒）之间的关联；该奖项将让她培养进行安全实验的技能，以确定激素变化的因果作用在自杀倾向中。培训成果包括激素实验技能、基于研究的自杀风险自杀相关结构的管理、生态瞬时评估和多模式测量。