The Influence of Estrogen on the Fear Extinction Network in Humans

描述(由申请人提供)：女性焦虑症的患病率是女性的两倍。流行率上升的原因尚不清楚，部分原因是大多数动物研究只使用男性，而大多数人类研究没有将性别作为一个感兴趣的变量。这项提案将通过以下方式开始检查这些差异的神经生物学基础 首先研究健康女性体内雌激素的自然波动如何影响恐惧消退网络的静息态活动和消退诱导的反应性，包括杏仁核、海马体和腹内侧额前皮质(VmPFC)。其他实验将涉及自然骑自行车的女性体内雌激素的外源性操作，以了解这些操作如何与恐惧消退网络的功能激活相互作用。健康的女性会在月经周期的不同阶段参与一套完善的恐惧调节和消除方案。功能磁共振成像和心理生理学工具将被用来检验两个总体假说：1)月经周期内自然升高的雌激素水平将促进恐惧消退网络的静息态活动和消退诱导的功能反应，并将与增强消退保持有关；2)外源性雌激素给女性将增强消退保持，这将与消亡回忆过程中该消退回路的增强的静息活动和消退诱导的功能反应有关。来自他的提案的发现可能有助于开发针对焦虑症的性别特异性治疗，例如，通过使用基于荷尔蒙的药理辅助药物来促进治疗过程中的安全学习。 与公共健康相关：大多数焦虑和情绪障碍的发病率在女性中是女性的两倍。这项建议将开始研究内源性和外源性雌激素水平对健康人恐惧消退网络功能活性和反应性的作用。 女人。如果成功，这种方法可能导致开发针对性别的治疗，以提高使用雌激素作为此类治疗的辅助手段的基于灭绝的治疗的结果。

DESCRIPTION (provided by applicant): The prevalence of anxiety disorders is twice as high in women. The reason for this eleveated prevalence is unclear, partly because most animal research has used only males, and most human research has not considered sex as a variable of interest. This proposal will begin to examine the neurobiological basis for these differences by first studying how natural fluctuations of estrogen in healthy women may influence the resting-state activity and the extinction-induced reactivity of the fear extinction network, including the amygdala, hippocampus, and the ventromedial prefrontal cortex (vmPFC). Additional experiments will involve exogenous manipulations of estrogen in naturally cycling women to see how these manipulations may interact with the functional activation of the fear extinction network. Healthy women will participate in a well-established fear conditioning and extinction protocol at different points of their menstrual cycle. Functional MRI and psychophysiological tools wil be employed to test two overall hypotheses: 1) Naturally elevated estrogen levels during the menstrual cycle will facilitate the resting-state activity and extinction-induced functional reactivity of the fear extinction network, and will be associated with enhanced extinction retention, and 2) Exogenous administration of estrogen to women will enhance extinction retention, which will be associated with enahnced resting-state activity and extinction-induced functional reactivity of this extinction circuitry during extinction recall. Findings from his proposal may help develop sex-specific treatments for anxiety disorders, for example by using hormonal-based pharmacological adjuncts to facilitate the processes of safety learning during therapy. PUBLIC HEALTH RELEVANCE: The incidence of most anxiety and mood disorders is twice as high in women. This proposal will begin to examine the role of endogenous and exogenous estrogen levels on the functional activity and reactivity of the fear extinction network in healthy women. If successful, this approach could lead to developing sex-specific treatments to enhance the outcome of extinction-based therapies using estrogen as an adjunct to such therapies.