Department of Psychology, University of Nebraska-Lincoln, Lincoln, Nebraska; Department of Psychiatry, University of Wisconsin-Madison, Madison, Wisconsin.
Department of Psychiatry, University of Wisconsin-Madison, Madison, Wisconsin.
Biol Psychiatry Cogn Neurosci Neuroimaging. 2020 Dec;5(12):1114-1122. doi: 10.1016/j.bpsc.2020.04.012. Epub 2020 Apr 30.
Fear responding in posttraumatic stress disorder (PTSD) is sexually heterogeneous and varies with hormonal fluctuations throughout the menstrual cycle. While research suggests that estrogen levels affect PTSD symptoms among women, there is a dearth of research on modulatory effects of estrogen on fear responding among women with PTSD, and neural outcome measures are lacking.
A sample of 42 women with PTSD underwent 2 consecutive alternating blocks of fear conditioning and extinction training, during which a CS+ conditioned stimulus, but not a CS-, predicted the occurrence of an electric shock in an acquisition context but not in an extinction context. Assayed saliva determined estradiol levels. Skin conductance response and whole-brain voxelwise activity during functional magnetic resonance imaging were outcome variables in linear mixed-effects models, with estradiol level, PTSD severity, and task contrasts as predictors.
Skin conductance response exhibited a significant estradiol × PTSD severity × habituation interaction (t = 3.180, p = .002), such that PTSD severity was correlated with increased arousal responding between training blocks among women with lower estradiol (t = -3.985, p < .001) but not higher estradiol (t = 0.550, p = .583). Voxelwise activity also demonstrated an identical three-way interaction within dorsomedial prefrontal cortex and anterior insula clusters. The skin conductance response and imaging interactions between PTSD severity and estradiol were not specific to conditioned stimulus type or context.
Estradiol moderated the relationship between PTSD severity and arousal response habituation between fear conditioning and extinction training sessions, such that high estradiol protected against the negative impact of severe PTSD symptoms on fear habituation. These findings suggest that estrogen enhances habituation among women with severe PTSD, potentially influencing the efficacy of extinction-based therapies.
创伤后应激障碍（PTSD）中的恐惧反应具有性别异质性，并且随着月经周期中的激素波动而变化。虽然研究表明雌激素水平会影响女性的 PTSD 症状，但对于 PTSD 女性中雌激素对恐惧反应的调节作用以及缺乏神经结果测量的研究还很少。
42 名患有 PTSD 的女性参加了 2 个连续的恐惧条件反射和消退训练交替块，在此期间，CS+条件刺激而不是 CS-，在获得性情境中预测电击的发生，但在消退性情境中不预测电击的发生。检测唾液确定雌二醇水平。功能磁共振成像期间的皮肤电导反应和全脑体素活动是线性混合效应模型中的因变量，以雌二醇水平、PTSD 严重程度和任务对比作为预测因子。
皮肤电导反应表现出显著的雌二醇×PTSD 严重程度×习惯化交互作用（t=3.180，p=0.002），即 PTSD 严重程度与较低雌二醇女性在训练块之间的唤醒反应增加相关（t=-3.985，p<0.001），而不是较高雌二醇（t=0.550，p=0.583）。脑区活动也在背内侧前额叶皮层和前岛叶簇中表现出相同的三向交互作用。PTSD 严重程度和雌二醇之间的皮肤电导反应和成像相互作用与条件刺激类型或情境无关。
雌二醇调节了 PTSD 严重程度与恐惧条件反射和消退训练之间的唤醒反应习惯化之间的关系，使得高雌二醇保护了严重 PTSD 症状对恐惧习惯化的负面影响。这些发现表明，雌激素增强了严重 PTSD 女性的习惯化，可能会影响基于消退的治疗的疗效。
