Distinct Steroid Mechanisms in Menstrual Cycle Exacerbation of Psychopathology

总结 生殖激素在月经周期中的变化可能是症状的关键生物学来源 精神病理学的变异性神经对正常激素变化的敏感性存在强烈的个体差异 可能导致广泛的情绪，人际关系和行为症状的不稳定性;然而， 这些效应背后的生物行为机制尚未得到很好的理解。边缘型人格障碍 (BPD)是一种严重和昂贵的精神疾病，包括许多领域的不稳定症状， 功能我们的试验数据表明，三种不同的生物学机制可能会产生基于周期的 症状加重，导致症状不稳定：1）反应性和人际症状， 孕酮（P4）水平变化引起的易怒，2）认知功能受损引起的抑郁症状 功能和增加反刍在雌激素（E2）撤退，和3）冒险症状， 在E2高峰期（排卵期）增加奖励反应。这项研究的目的是测试一个 三个RDoC一致的基于生物学的机制的模型，这些机制是月经周期如何 会加剧精神病理将招募170名年龄在18至45岁之间、具有≥3种BPD症状的女性样本 从专业的临床服务和社交媒体。参与者将接受全面的BPD评估， 排除标准（例如，使用基于激素的药物或激素状况）。参与者将完成 BPD和其他精神病理学症状和诊断的成熟评估措施， 在月经周期开始的前几天内进行基线实验室检查。然后，他们会 每天晚上提供关于BPD症状和拟议机制的完整问卷， 完整的循环。在一个周期中，他们将根据月经完成针对关键周期阶段的任务 开始和排卵测试结果，以及每天早晨用于激素测定的每日尿液样本。具体目标。 目的1是评估是否变化的激素跨周期预测内的个人变化的症状 与提出的三元激素敏感性理论一致，随着P4水平的升高， 拒绝敏感性、人际冲突和应激冲动反应，降低E2水平预测 抑郁、绝望和自杀意念增加，E2（排卵）峰值预测增加 主动攻击和滥用药物目的2是评估是否提出心理 激素变化和症状影响之间的调节机制， 易怒预期介导P4效应，认知功能下降预期介导E2戒断 影响，特别是对于具有更大反刍倾向和增加奖励反应的个体 预期介导排卵作用。探索性目标3将检查这些因素的存在程度， 三种形式的激素敏感性是相关的。研究结果将为个性化， transdiagnosis干预，以减轻基于周期的症状加重的影响。

SUMMARY Changes in reproductive hormones across the menstrual cycle may be a key biological source of symptom variability in psychopathology. Strong individual differences in neural sensitivity to normal hormone changes can result lability of a wide range of emotional, interpersonal, and behavioral symptoms; however, the biobehavioral mechanisms underlying these effects are not yet well understood. Borderline personality disorder (BPD) is a severe and costly psychiatric condition comprising labile symptoms across many domains of functioning. Our pilot data suggest three distinct biologically based mechanisms may produce cycle-based symptom exacerbation, contributing to symptom lability: 1) reactive and interpersonal symptoms due to irritability from changes in progesterone (P4) levels, 2) depressive symptoms due to impaired cognitive functioning and increased rumination during estrogen (E2) withdrawal, and 3) risk-taking symptoms due increased reward responsiveness during E2 peaks (ovulation). The objectives of this research are to test a model of three RDoC-consistent biologically-based mechanisms underlying how the menstrual cycle exacerbates psychopathology. A sample of 170 women ages 18 to 45 with ≥3 BPD symptoms will be recruited from specialized clinical services and social media. Participants will be comprehensively assessed for BPD and exclusion criteria (e.g., use of hormone-based medication or hormonal conditions). Participants will complete well-established assessment measures of BPD and other psychopathological symptoms and diagnoses during a baseline laboratory visit within the within the first few days of the start of their menstrual cycle. Then, they will provide complete questionnaires about BPD symptoms and proposed mechanisms every evening for two complete cycles. During one cycle, they will complete tasks targeted to key cycle phases, based on menses onset and ovulation test results, and daily urine samples for hormone assay each morning. Specific Aims. Aim 1 is to evaluate whether shifts in hormones across cycle predict within-person changes in symptoms consistent with proposed triadic hormone sensitivity theory, with rising levels of P4 predicting increases in rejection sensitivity, interpersonal conflict, and impulsive reactivity to stress, decreasing levels of E2 predicting increases in depression, hopelessness, and suicidal ideation, and peaks in E2 (ovulation) predicting increases in proactive aggression and substance misuse. Aim 2 is to evaluate whether proposed psychological mechanisms mediation associations between hormonal changes and symptom effects, with increased irritability expected to mediate P4 effects, decreased cognitive functioning expected to mediate E2 withdrawal effects, especially for individuals with greater rumination-proneness, and increased reward responsiveness expected to mediate ovulatory effects. An exploratory Aim 3 will examine the extent to which presence of these three forms of hormone sensitivity are associated. Findings will inform development of individualized, transdiagnostic interventions to mitigate the impact of cycle-based symptom exacerbation.