A Multi-Modal Investigation of Neurophysiological Deficits in PTSD

项目摘要 女性被诊断为创伤后应激障碍(PTSD)和性激素的可能性是男性的两倍 都与这一差异有牵连。虽然研究已经开始阐明神经生理学的贡献 对于创伤后应激障碍，缺乏关于性激素如何影响这些动力以赋予更大权力的知识。 女性中的风险。例如，尽管创伤后应激障碍通常与增加的静息状态活动有关，但 背侧前扣带回皮质(DACC)和腹内侧额叶皮质(VmPFC)活动降低， 与男性相比，女性在这些地区的活跃度可能较低。其他研究表明，创伤后应激障碍 与额叶脑区功能连通性降低有关。然而，此前没有任何研究表明 在男性和女性中测试了dACC-vmPFC功能连接，这可以提供对 创伤后应激障碍性别差异的机制。此外，低雌二醇和高孕酮一直是 与患有创伤后应激障碍的女性更严重的恐惧抑制有关，睾丸素水平与 男性中的创伤后应激障碍，尽管研究结果好坏参半。此前没有研究检验性激素水平如何 调节创伤后应激障碍的dACC-vmPFC活性或功能连接，还没有研究比较这些 对男性和女性的影响。这一拟议的补编将通过增加一个新的 正在进行的父母K23研究中的男性样本，以及通过在现有的 雌二醇和黄体酮。通过检测性激素(雌二醇、孕酮、睾酮)对 无论是男性还是女性，这项建议都将描述性别在神经生理缺陷中的作用 可见于创伤后应激障碍。拟议的补编将嵌入现有的母公司K23研究，该研究已 到目前为止，已经招募了60名女性。该补充资料将包括30名患有创伤后应激障碍的男性的新样本。的目标 母公司K23和这项拟议的补充方案直接符合2019-2023年交通运输的战略目标1- 美国国立卫生研究院妇女健康研究战略计划：“推进与妇女健康相关的严谨研究 女人。“具体而言，目标1.2是“调查性别和性别对疾病表现的影响”。 拟议的补充内容将探讨三种不同的性激素(性)在 男性和女性创伤后应激障碍患者的神经生理缺陷。

Project Summary Women are twice as likely as men to be diagnosed with posttraumatic stress disorder (PTSD), and sex hormones have been implicated in this difference. While research has begun to elucidate neurophysiological contributions to PTSD, there is a dearth of knowledge regarding how sex hormones influence these dynamics to confer greater risk among women. For example, while PTSD is generally associated with increased resting state activity of the dorsal anterior cingulate cortex (dACC) and decreased activity of the ventromedial prefrontal cortex (vmPFC), women may exhibit lower activity in these regions compared to men. Other research has shown that PTSD is associated with decreased functional connectivity of frontal brain regions. However, no prior research has tested dACC-vmPFC functional connectivity in men versus women, which could provide insight into mechanisms underlying PTSD sex differences. Further, low estradiol and high progesterone have been associated with worse fear inhibition in women with PTSD, and testosterone levels have been implicated in PTSD among men, though findings are mixed. No prior studies have examined how sex hormone levels modulate dACC-vmPFC activity or functional connectivity in PTSD, and no studies have compared these effects in men versus women. This proposed supplement will directly address these gaps by adding a new sample of men to the ongoing Parent K23 study, as well as by adding testosterone assays to existing assays of estradiol and progesterone. By examining the effects of sex hormones (estradiol, progesterone, testosterone) in both men and women, this proposal will characterize the role of sex in the neurophysiological deficits seen in PTSD. The proposed supplement will be embedded within the existing Parent K23 study, which has recruited 60 women thus far. The supplement will include a new sample of 30 men with PTSD. The goals of the Parent K23 and this proposed supplement are directly in line with Strategic Goal 1 of the 2019-2023 Trans- NIH Strategic Plan for Women's Health Research: “Advance rigorous research that is relevant to the health of women.” In particular, Objective 1.2 is to “Investigate the influence of sex and gender on disease presentation,” and the proposed supplement will probe the role of three different sex hormones (sex) on neurophysiological deficits in both men and women with PTSD.