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

基本信息

批准号：
10894366
负责人：
Jennifer Strafford Stevens
金额：
$ 11.75万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
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/10894366
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&apos 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

项目摘要

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.

项目摘要大多数美国人一生都会遇到一场创伤事件，但女性的两倍在创伤之类的创伤之后，可能会经历负面的精神病结果，例如创伤后压力障碍（PTSD）和抑郁症。女性患病率增加的原因尚不清楚，部分原因由于历史上缺乏对人类和临床前动物研究中女性的研究。在拟议的研究，我们将研究性激素在促进女性PTSD风险的作用。这性腺激素雌二醇（E2）以前与情绪调节和恐惧灭绝有关啮齿动物和健康的人类研究，由杏仁核和调节性之间的途径中的可塑性介导前额叶皮层和海马的输入。具有PTSD的妇女在调节方面表现出明显的缺陷情绪唤醒，并在恐惧的灭绝学习中。我们将检验以下假设，即低E2有助于这些通过实验操纵E2的缺陷，并研究其对fMRI威胁反应性和害怕灭绝，患有PTSD的女性，暴露于PTSD的女性和健康对照。我们将使用随机的双盲，安慰剂对照，主体内部跨界设计，E2/安慰剂给予当内源性E2最低时，在周期的早期卵泡阶段，天然循环的女性。参与者将在第一次MRI扫描时随机分配到E2或安慰剂，并将跨越其他条件在随后的月经周期中在同一点进行的第二次扫描。其次，给定现有观察性证据表明，在黄体阶段增加了PTSD风险/症状，我们将测试E2 在黄体阶段给药，以观察E2-预耐酮比的增加是否会降低PTSD 在这个风险增加的时代，威胁反应性和恐惧灭绝的症状和障碍。研究埃默里大学医学院的环境将为成功的成功提供极大的支持拟议研究的完成，尤其是在最先进的神经影像学设施的情况下，一个发达的通过Grady创伤项目识别有创伤和PTSD风险的参与者的基础设施，创伤，神经内分泌，神经影像学和妇女健康研究专家的强大专家社区。发现从这项研究中可以帮助发展新的治疗和干预措施，以增加妇女的精神创伤后的健康结果。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Association between perimenopausal age and greater posttraumatic stress disorder and depression symptoms in trauma-exposed women.

遭受创伤的女性围绝经期年龄与更大的创伤后应激障碍和抑郁症状之间的关联。

DOI：
10.1097/gme.0000000000002235
发表时间：
2023
期刊：
Menopause (New York, N.Y.)
影响因子：
0
作者：
Michopoulos,Vasiliki;Huibregtse,MeganE;Chahine,EBritton;Smith,AliciaK;Fonkoue,IdaT;Maples-Keller,Jessica;Murphy,Amy;Taylor,Linzie;Powers,Abigail;Stevens,JenniferS
通讯作者：
Stevens,JenniferS

Validating the primary care posttraumatic stress disorder screen for DSM-5 (PC-PTSD-5) in a substance misusing, trauma-exposed, socioeconomically vulnerable population.

在滥用药物、遭受创伤、社会经济弱势群体中验证 DSM-5 (PC-PTSD-5) 初级保健创伤后应激障碍筛查。

DOI：
10.1016/j.addbeh.2022.107592
发表时间：
2023
期刊：
Addictive behaviors
影响因子：
4.4
作者：
Patton,SamanthaC;Hinojosa,CeciliaA;Lathan,EmmaC;Welsh,JustineW;Powers,Abigail
通讯作者：
Powers,Abigail

Hippocampal activation during contextual fear inhibition related to resilience in the early aftermath of trauma.

DOI：
10.1016/j.bbr.2021.113282
发表时间：
2021-06-25
期刊：
Behavioural brain research
影响因子：
2.7
作者：
van Rooij SJH;Ravi M;Ely TD;Michopoulos V;Winters SJ;Shin J;Marin MF;Milad MR;Rothbaum BO;Ressler KJ;Jovanovic T;Stevens JS
通讯作者：
Stevens JS

Association between dimensions of trauma-related psychopathology and asthma in trauma-exposed women.

DOI：
10.3389/fnbeh.2023.1268877
发表时间：
2023
期刊：
Frontiers in behavioral neuroscience
影响因子：
3
作者：
通讯作者：

Posttraumatic stress disorder and breast cancer: Risk factors and the role of inflammation and endocrine function.

DOI：
10.1002/cncr.32934
发表时间：
2020-07-15
期刊：
CANCER
影响因子：
6.2
作者：
Brown, Lauren C.;Murphy, Amy R.;Lalonde, Chloe S.;Subhedar, Preeti D.;Miller, Andrew H.;Stevens, Jennifer S.
通讯作者：
Stevens, Jennifer S.