Stress response and neural network function in women with vasomotor symptoms

有血管舒缩症状的女性的应激反应和神经网络功能

• 批准号: 10669210
• 负责人: HADINE JOFFE
• 金额: $ 38.93万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10669210
• 关键词: Acute; Adrenal Cortex Hormones; Affect; Aging; Anterior; Anxiety; Autonomic nervous system; Behavior Therapy; Biological; Brain; Brain region; Cardiometabolic Disease; Cardiovascular Diseases; Chronic stress; Data; Dementia; Dynorphins; Educational process of instructing; Exhibits; Faculty; Functional Magnetic Resonance Imaging; Goals; Health; High Prevalence; Hippocampus; Hot flushes; Institution; Insula of Reil; Intervention; Investigation; KISS1 gene; Link; Magnetic Resonance Spectroscopy; Measures; Mediating; Mental Depression; Mentors; Metabolic Diseases; Methodology; Neurons; Neurophysiology - biologic function; Neurotransmitters; Night Sweating; Outcome; Pain; Pathway interactions; Play; Postmenopause; Predisposition; Prevention; Process; Psychosocial Stress; Public Health; Quality of life; Resources; Risk; Role; Sleep; Sleep disturbances; Stress; Symptoms; Testing; Woman; acute stress; biological adaptation to stress; cardiometabolism; career; cingulate cortex; cohort; common symptom; comorbidity; follow-up; gamma-Aminobutyric Acid; hormone therapy; hypothalamic-pituitary-adrenal axis; improved; improvement on sleep; innovation; neural; neural network; neurobiological mechanism; neuroregulation; novel; participant enrollment; perceived stress; predict responsiveness; reproductive senescence; response; targeted treatment; vasomotor symptoms

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.

布里格姆/哈佛SCORE压力和神经调节中心的项目1的广泛目标是： 生殖衰老健康结果是通过确定压力来促进绝经后妇女的健康 血管痉挛症状（VMS）发生和持续的反应性，并表征神经过程 以及VMS与应激反应之间的神经生物学机制。VMS是最常见的症状 绝经期和绝经后，发生在高达85%的女性中，平均持续7.4-9.0年，并持续存在 在33-40%的绝经后妇女中持续10年以上。对VMS的应力机制的研究 由于其高流行率、对生活质量的影响和对健康的不利影响， 相互关联VMS会扰乱睡眠，并与心脏代谢疾病有关，心脏代谢疾病以及 激素疗法用于治疗VMS，增加老年妇女对痴呆症的易感性。我们提出了一种新 根据我们的初步数据和其他人的数据，将VMS概念化为一种慢性应激状态， 应激反应与VMS的关系。不同性别女性对诱发应激反应的差异 VMS表明压力相关神经网络的潜在中断（例如，前扣带皮层， 海马，眶额皮质，海马）和抑制性神经递质γ-氨基丁酸 （GABA），其调节压力网络，如在慢性压力条件下所见（例如，焦虑、疼痛）。 失调的应激反应可能反映了应激介导VMS的神经过程。项目1将 创新性地将诱发应激范式的稳健方法学与最先进的功能性方法学联合收割机 磁共振成像和磁共振波谱学对急性应激进行横断面研究 有或无VMS的女性中的反应性、神经网络功能和GABA浓度 项目2（Viva项目组群）。我们将纵向确定神经应激网络的失调是否 和GABA预测VMS的持续性超过2年的随访期。与睡眠资源 核心（SRC），我们将研究是否睡眠中断共病VMS进一步钝化急性压力 响应性同样，我们将测试是否感知压力有助于不同的压力反应 在VMS患者中的失调。项目1通过注册纳入布里格姆/哈佛评分 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 与项目3并行的VMS潜在压力过程，利用SRC获得的睡眠指标，以及 通过职业提升核心来教授和指导初级教师和学员。利用这些 协同SCORE和广泛的布里格姆/哈佛机构资源，我们的研究将使主要 通过确定与VMS相关的神经应激机制， 指出VMS的新疗法也可能改善睡眠和心脏代谢健康， 老年妇女痴呆症易感性的意义。