Neuroendocrine Mechanisms of Risk for Trauma-Related Psychopathology in Women

女性创伤相关精神病理学风险的神经内分泌机制

• 批准号: 10600004
• 负责人: Jennifer Strafford Stevens
• 金额: $ 62.23万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-16 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10600004
• 关键词: Acute; Affect; American; Amygdaloid structure; Animal Experimentation; Anti-Anxiety Agents; Anxiety Disorders; Arousal; Brain; Chronic Disease; Communities; Control Groups; Cross-Over Studies; Crossover Design; Data; Development; Diagnosis; Diagnostic; Disease; Dose; Double-Blind Method; Emotional; Environment; Epidemiology; Estradiol; Exposure to; Extinction; Face; Female; Fright; Functional Magnetic Resonance Imaging; Goals; Gonadal Hormones; Gonadal Steroid Hormones; Gonadal structure; Healthcare; Hippocampus; Hormonal; Hormones; Human; Human Subject Research; Impairment; Incidence; Infrastructure; Intervention; Investigation; Link; Luteal Phase; MRI Scans; Measures; Mediating; Memory; Menstrual cycle; Mental Depression; Mental Health; Mental disorders; Mood Disorders; Nature; Neurobiology; Neurosecretory Systems; Outcome; Ovarian hormone; Participant; Pathway interactions; Phenotype; Placebo Control; Placebos; Play; Post-Traumatic Stress Disorders; Prefrontal Cortex; Prevalence; Process; Progesterone; Psychopathology; Puberty; Randomized; Recording of previous events; Research; Risk; Risk Factors; Rodent; Role; Sampling; Scanning; Sex Differences; Stimulus; Symptoms; Synaptic plasticity; Testing; Time; Trauma; United States; Universities; Woman; Women' s Health; Work; brain based; cohort; conditioned fear; emotion regulation; experience; health disparity; high risk; improved; learning extinction; male; medical schools; men; neuroimaging; pre-clinical; proliferative phase Menstrual cycle; recruit; response; severe psychiatric disorder; sex; trauma exposure; traumatic event; traumatic stress; young woman

Project Summary The majority of Americans will experience a traumatic event during their lifetimes, but women are twice as likely as men to experience negative psychiatric outcomes following trauma such as post-traumatic stress disorder (PTSD) and depression. The reason for the increased prevalence in women is unclear, partially because of the historical lack of investigation of females in both human and pre-clinical animal research. In the proposed research, we will investigate the role of sex hormones in contributing to women's risk for PTSD. The gonadal hormone estradiol (E2) has previously been associated with emotion regulation and fear extinction in rodent and healthy human studies, mediated by plasticity in pathways between the amygdala and regulatory inputs from the prefrontal cortex and hippocampus. Women with PTSD show clear deficits in regulating emotional arousal, and in fear extinction learning. We will test the hypothesis that low E2 contributes to these deficits by experimentally manipulating E2, and studying its effects on fMRI measures of threat reactivity and fear extinction, in women with PTSD, trauma-exposed women without PTSD, and healthy controls. We will use a randomized double-blind, placebo-controlled, within-subjects crossover design, with E2/placebo given to naturally-cycling women during the early follicular phase of the cycle when endogenous E2 is lowest. Participants will be randomized to E2 or placebo at the first MRI scan, and will cross over to the other condition for a second scan conducted at the same point in the subsequent menstrual cycle. Secondly, given existing observational evidence that PTSD risk/symptoms are heightened during the luteal phase, we will test this E2 administration in the luteal phase to observe whether an increase in the E2-progesterone ratio reduces PTSD symptoms and impairments in threat reactivity and fear extinction in this time of heightened risk. The research environment at Emory University School of Medicine will provide excellent support for the successful completion of the proposed research, particularly with state of the art neuroimaging facilities, a well-developed infrastructure for identifying participants at risk for trauma and PTSD through the Grady Trauma Project, and a strong community of experts in trauma, neuroendocrine, neuroimaging, and women's health research. Findings from this study may aid in the development of new treatments and interventions to increase women's mental health outcomes following trauma.

项目概要 大多数美国人在一生中都会经历创伤性事件，但女性的比例是女性的两倍 男性在创伤后可能会经历负面的精神后果，例如创伤后应激障碍 障碍（PTSD）和抑郁症。女性患病率增加的原因尚不清楚，部分原因是 因为在人类和临床前动物研究中历史上缺乏对女性的调查。在 在拟议的研究中，我们将调查性激素在增加女性患创伤后应激障碍（PTSD）风险方面的作用。这 性腺激素雌二醇（E2）先前被认为与情绪调节和恐惧消除有关。 啮齿动物和健康人类研究，由杏仁核和调节之间通路的可塑性介导 来自前额皮质和海马体的输入。患有创伤后应激障碍 (PTSD) 的女性在调节方面表现出明显的缺陷 情绪唤起，以及在恐惧消退中学习。我们将检验低 E2 导致这些的假设 通过实验操纵 E2 来弥补缺陷，并研究其对威胁反应性和功能磁共振成像测量的影响 患有 PTSD 的女性、没有 PTSD 的遭受创伤的女性以及健康对照者的恐惧消失。我们将使用 随机双盲、安慰剂对照、受试者内交叉设计，给予 E2/安慰剂 处于自然周期的女性在周期的早期卵泡阶段，此时内源性 E2 最低。 参与者将在第一次 MRI 扫描时被随机分配到 E2 组或安慰剂组，然后会交叉到其他条件组 在随后的月经周期的同一点进行第二次扫描。其次，鉴于现有 观察证据表明 PTSD 风险/症状在黄体期加剧，我们将测试此 E2 在黄体期给药，观察 E2-黄体酮比率的增加是否可以减轻 PTSD 在这个风险较高的时期，威胁反应和恐惧消退的症状和损害。研究 埃默里大学医学院的环境将为成功提供良好的支持 完成拟议的研究，特别是使用最先进的神经影像设备、一个成熟的 通过 Grady 创伤项目识别有创伤和 PTSD 风险的参与者的基础设施，以及 创伤、神经内分泌、神经影像和妇女健康研究方面强大的专家社区。发现 这项研究可能有助于开发新的治疗方法和干预措施，以提高女性的心理健康水平 创伤后的健康结果。