Adolescent Girls’ Risk for Suicide Across the Menstrual Cycle: Examining Stress and Negative Valence Systems Longitudinally

项目总结/摘要 自杀是美国10 - 34岁人群的第二大死亡原因（仅次于事故）， 是与精神疾病联系最紧密的死亡原因。从大约12岁开始， 自杀想法和行为（STBs）的发生率急剧上升，特别是在经历STBs的女孩中 是男孩的两倍青少年和女孩的这种明显增加有据可查 几十年来，几乎在世界各地的每个国家/文化中都可以看到，然而，没有确切的理解 它们存在的原因此外，人们对什么时候风险最高知之甚少。这项研究扩展了我们的 研究小组先前的工作，由两个先前的R01奖资助，研究青春期女孩的压力反应， STB轨迹的预测因素，以及K99/R00奖揭示了生殖激素的变化， 月经周期产生特定时期的高STB风险（特别是在月经期） 在成年女性中。具体来说，我们假设女孩将报告更高的发病率和严重程度的性病 月经期天数多于其他周期阶段（卵泡中期、排卵期、黄体中期）天数， 这些增加将介导的日常变化，在负面影响和压力反应， 月经期，周期性激素敏感性更高的女孩患性病的长期风险更大， 特别是在人际关系紧张的时候。我们建议在样本中测试这些假设 200名年龄在12 - 17岁之间、月经初潮后至少一年的临床转诊女孩。设计开始 70天（两个周期）的日常调查，以评估负面影响和STBs。此外，女生还将完成两项 平衡实验室访视（在高风险围月经期和低风险卵泡中期），在此期间，我们 将评估他们的情感和生理（自主神经，皮质醇，基因组）反应，以标准化的 实验室应激源接下来，女孩们将完成每周一次的调查，测量周期阶段，人际压力， 负面影响，和性病通过一年的随访。为期两个月的密集基线阶段使我们能够 检查月经周期如何塑造STBs的日常情感和生理风险，并让我们诊断 每个女孩的荷尔蒙敏感度这些激素敏感性的基线个体差异可以 在后续评估年，特别是在 增加社会压力。这种强大的设计将澄清是否在每日STB（目标1）的周期性变化， 由情感和生理STB风险因素介导，如负面影响（目标2a;通过每日测量 调查）和社会压力反应（目标2b;通过基于实验室的行为，生理和分子测量 生物标志物测定），同时也承认激素水平的个体差异 灵敏度（即，并非所有女孩都会有严重的周期性情绪变化）和随时间变化的人际压力（Aim 3）。这项创新的研究将解决文献中几个长期存在的问题，包括为什么女孩在 增加的风险，当女孩可能是最危险的，以及哪些女孩是在未来的性传播感染的风险最高。

Project Summary/Abstract Suicide is the second leading cause of death (behind accidents) among those ages 10-34 years in the US and is the cause of mortality most strongly linked to mental illness. Starting at approximately age 12 years, the rate of suicidal thoughts and behaviors (STBs) increases dramatically, especially among girls, who experience STBs at twice the rate for boys. These pronounced increases for adolescents and for girls have been well-documented for decades and are seen in virtually every country/culture around the world, yet, there is no firm understanding of why they exist. Moreover, very little is known about when risk is highest. The proposed research extends our team’s prior work, funded by two prior R01 awards, examining adolescent girls’ stress responses as prospective predictors of STB trajectories, and a K99/R00 award revealing that changes in reproductive hormones across the menstrual cycle produce specific periods of high STB risk (particularly during the peri-menstrual phase) among adult women. Specifically, we hypothesize that girls will report higher occurrence and severity of STBs on days in the peri-menstrual phase than on days in other cycle phases (mid-follicular, ovulatory, mid-luteal), that these increases will be mediated by daily changes in negative affect and stress-reactivity during the peri- menstrual phase, and that girls with greater cyclical hormone sensitivity are at greater long-term risk of STBs, particularly during times when interpersonal stress is elevated. We propose to test these hypotheses in a sample of 200 clinically-referred girls ages 12-17 years who are at least one year post-menarche. The design begins with 70 days (two cycles) of daily surveys to assess negative affect and STBs. In addition, girls will complete two counterbalanced laboratory visits (at high risk peri-menstrual and low risk mid-follicular phases) during which we will evaluate their affective and physiological (autonomic, cortisol, genomic) responses to a standardized laboratory stressor. Next, girls will complete weekly surveys measuring cycle phase, interpersonal stress, negative affect, and STBs through one year of follow up. The intensive two-month baseline phase allows us to examine how the menstrual cycle shapes daily affective and physiological risk for STBs and lets us diagnose each girl’s degree of hormone sensitivity. These baseline individual differences in hormone sensitivity then can be examined as a predictor of STBs across the follow-up year of assessments, particularly during periods of elevated social stress. This powerful design will clarify whether cyclical changes in daily STBs (Aim 1) are mediated by affective and physiological STB risk factors, such as negative affect (Aim 2a; measured via daily surveys) and social stress reactivity (Aim 2b; measured via lab-based behavioral, physiological, and molecular biomarker assays), while also acknowledging critical moderation by both individual differences in hormone sensitivity (i.e., not all girls will have severe cyclical mood changes) and time-varying interpersonal stress (Aim 3). This innovative study will address several long-standing questions in the literature, including why girls are at increased risk, when girls may be most at risk, and which girls are at highest risk for future STBs.