Distinct Steroid Mechanisms in Menstrual Cycle Exacerbation of Psychopathology

月经周期加剧精神病理学的独特类固醇机制

• 批准号: 10636886
• 负责人: Jessica Rachael Peters
• 金额: $ 58.75万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-15 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10636886
• 关键词: Age; Aggressive behavior; Alcohol consumption; Anger; Automobile Driving; Behavior; Behavioral; Behavioral Mechanisms; Behavioral Symptoms; Biological; Biological Assay; Borderline Personality Disorder; Characteristics; Clinical Services; Data; Depressive disorder; Development; Diagnosis; Diagnostic; Down-Regulation; Eating Disorders; Emotional; Emotions; Estrogens; Exclusion Criteria; Family; Feeling hopeless; Feeling suicidal; Female; Health Personnel; Health system; Heterogeneity; Hormonal; Hormonal Change; Hormone use; Hormones; Impaired cognition; Impulsivity; Individual; Individual Differences; Intervention; Laboratories; Link; Longitudinal Studies; Luteal Phase; Measures; Mediating; Mediation; Menstrual cycle; Menstruation; Mental Depression; Mental Health; Mental disorders; Modeling; Nature; Ovarian hormone; Ovulation; Participant; Patient Self-Report; Pattern; Persons; Pharmaceutical Preparations; Phase; Progesterone; Psychopathology; Questionnaires; Research; Research Domain Criteria; Rewards; Risk Taking; Sampling; Source; Steroids; Stress; Substance abuse problem; Suicide; Symptoms; Test Result; Testing; Theory of Change; Urine; Visit; Withdrawal; Woman; associated symptom; binge drinking; biobehavior; clinically significant; cognitive capacity; cognitive function; cost; depressive symptoms; diaries; experience; falls; hormone sensitivity; improved; interpersonal conflict; motivated behavior; neural; novel; pharmacologic; proliferative phase Menstrual cycle; psychologic; psychosocial; recruit; reproductive hormone; rumination; social; social media; substance misuse; substance use; suicidal; theories; trait

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.

摘要 月经周期中生殖激素的变化可能是症状的关键生物学来源 精神病理学中的变异性。神经对正常激素变化的敏感度存在很大的个体差异 可导致一系列情绪、人际关系和行为症状的易感性；然而， 这些影响背后的生物行为机制还没有被很好地理解。交界性人格障碍 (BPD)是一种严重且代价高昂的精神疾病，包括许多领域的不稳定症状 功能正常。我们的试验数据表明，三种不同的基于生物的机制可能产生基于周期的 症状加重，导致症状不稳定：1)因以下原因引起的反应性和人际关系症状 孕酮(P4)水平变化引起的易怒，2)认知障碍引起的抑郁症状 在雌激素(E2)停用期间的功能和反省增加，以及3)由于 在雌二醇峰(排卵)期间增加奖励反应性。这项研究的目的是测试一个 三种RDoC一致的生物学机制的模型，这些机制是如何影响月经周期的 加剧了精神病的病态。将招募170名年龄在18岁到45岁之间、有≥3bpd症状的女性作为样本。 来自专业临床服务和社交媒体。将对参与者进行全面的BPD和 排除标准(例如，使用以激素为基础的药物或激素状况)。参赛者将完成 建立完善的BPD和其他精神病理症状和诊断的评估措施 在月经周期开始的头几天内，在月经周期开始前几天内进行基线实验室检查。然后，他们会 每晚为两人提供关于BPD症状和建议机制的完整问卷 完整的循环。在一个周期内，他们将根据月经情况完成针对关键周期阶段的任务 开始和排卵试验结果，每日早晨取尿样进行激素测定。明确的目标。 目标1是评估荷尔蒙在周期中的变化是否能预测人内症状的变化。 与提出的三种激素敏感性理论一致，P4水平上升预示着 拒绝敏感性、人际冲突和对压力的冲动反应，E2水平下降预测 抑郁、绝望和自杀意念的增加，以及E2(排卵)峰值的增加 积极主动的攻击性和物质滥用。目标2是评估所提出的心理问题 激素变化和症状效应之间的调节机制，增加了 易怒预计将中介P4效应，认知功能下降预计将中介E2戒断 效果，特别是对于有更大反省倾向和更高奖励反应性的个人 预计能调节排卵效果。探索性目标3将检查这些问题的存在程度 三种形式的激素敏感性是相关的。研究结果将为个性化、 跨诊断干预措施，以减轻基于周期的症状恶化的影响。