Stress response and neural network function in women with vasomotor symptoms

布里格姆/哈佛大学压力和神经调节中心项目1的总体目标是 生殖老龄化健康结果是通过确定压力来促进绝经后妇女的健康 血管运动症状(VMS)发生和持续的反应性及其神经过程的特征 以及将VMS与应激反应联系起来的神经生物学机制。VMS是最常见的症状 在绝经期间和绝经后，高达85%的女性发生，平均持续7.4-9.0年，并持续 在33-40%的绝经后妇女中持续10年以上。VMS背后的应激机制的研究有 由于其高患病率、对生活质量的影响和不良健康，具有重要的公共卫生意义 相互关联。VMS会扰乱睡眠，并与心脏代谢性疾病有关，这种疾病与 激素疗法用于治疗VMS，增加老年女性患痴呆症的易感性。我们提议写一部小说 根据我们的初步数据和其他人的研究结果，将VMS概念化为慢性应激状态 应激反应与VMS的关系。患有精神分裂症的女性对诱发压力任务的反应性差异 VMS提示应激相关神经网络(例如，前扣带回皮质， 海马区、额叶皮质、脑岛)和抑制性神经递质γ-氨基丁酸 (GABA)，它调节压力网络，如在慢性压力条件下(如焦虑、疼痛)。 失调的应激反应可能反映了应激通过其中介VMS的神经过程。项目1将 创新性地将诱发应激范例的稳健方法与最先进的功能 磁共振成像和磁共振波谱横断面研究急性应激反应 有无VMS的女性的反应性、神经网络功能和GABA浓度 项目2(万岁项目队列)。我们将纵向确定神经应激网络的失调 GABA预测VMS持续2年以上。与睡眠资源相结合 CORE(SRC)，我们将研究睡眠中断与VMS共病是否会进一步钝化急性应激 责任感。同样，我们将测试感知到的压力是否对压力反应有不同的贡献。 患有多发性硬化症的人存在调节失调。通过招生，项目1被整合到布里格姆/哈佛的分数中 参与者，并从项目2队列中获得相关的纵向数据，检查机械神经 Stress利用SRC获得的睡眠指标，与项目3并行地处理潜在的VMS，以及 通过职业提升核心为初级教师和实习生提供教学和指导。利用这些优势 协同得分和广泛的布里格姆/哈佛院校资源，我们的研究将使主要 通过确定与VMS相关的神经应激机制对老年女性的健康做出贡献-潜在地 指出VMS的新治疗方法也可能改善睡眠和心脏代谢健康，下游 对老年女性痴呆症易感性的影响。

The broad goal of Project 1 of the Brigham/Harvard SCORE Center for Stress and Neural Regulation of Reproductive Aging Health Outcomes is to advance the health of postmenopausal women by determining stress responsivity in vasomotor symptoms (VMS) occurrence and persistence and to characterize neural processes and neurobiological mechanisms linking VMS with stress responsivity. VMS are the most common symptoms during and after menopause, occurring in up to 85% of women, lasting 7.4–9.0 years on average, and persisting for 10+ years in 33–40% of postmenopausal women. Investigations of stress mechanisms underlying VMS have important public health significance due to their high prevalence, impact on quality of life, and adverse health correlates. VMS disrupt sleep and are associated with cardiometabolic disease, which, together with risks of hormone therapy used to treat VMS, increase susceptibility to dementia in aging women. We propose a novel conceptualization of VMS as a chronic stress condition based on our preliminary data and that of others indicating associations of stress responsivity with VMS. Differences in responsivity to evoked stress tasks in women with VMS suggest underlying disruptions in stress-related neural networks (e.g., anterior cingulate cortex, hippocampus, orbitofrontal cortex, insula) and in the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), which regulates stress networks, as is seen in chronic stress conditions (e.g., anxiety, pain). Dysregulated stress responses may reflect neural processes through which stress mediates VMS. Project 1 will innovatively combine the robust methodology of an evoked stress paradigm with state-of-the-art functional magnetic resonance imaging and magnetic resonance spectroscopy to cross-sectionally investigate acute stress responsivity, neural network function, and GABA concentrations in women with and without VMS referred by Project 2 (Project Viva cohort). We will determine longitudinally whether dysregulation of neural stress networks and GABA predict persistence of VMS over a 2-year follow-up period. In conjunction with the Sleep Resource Core (SRC), we will examine whether sleep disruption comorbid with VMS further blunts acute stress responsivity. Similarly, we will test whether perceived stress contributes differentially to stress response dysregulation in those with VMS. Project 1 is integrated within the Brigham/Harvard SCORE, through enrolling participants and obtaining relevant longitudinal data from the Project 2 cohort, examining mechanistic neural stress processes underlying VMS in parallel with Project 3, utilizing sleep metrics obtained by the SRC, and teaching and mentoring junior faculty and trainees through the Career Enhancement Core. Leveraging these synergistic SCORE and extensive Brigham/Harvard institutional resources, our study will make major contributions to the health of aging women by identifying neural stress mechanisms linked to VMS—potentially pointing to novel treatments for VMS that may also improve sleep and cardiometabolic health, with downstream implications for dementia susceptibility in aging women.