Dissecting the role of estradiol in mediating gender-specific anxiolytic and prosocial effects of oxytocin

焦虑症是最常见的精神疾病之一，相当大比例的患者无法从现有的治疗方法中获益。神经肽催产素（OXT）具有抗焦虑和亲社会的特性，因此可以用作增强现有疗法的辅助剂。然而，焦虑症的患病率和OXT的社会影响在男女之间存在很大差异。因此，本项目的目的是研究性别特异性的影响，OXT在健康的参与者和探测OXT和性类固醇雌二醇之间的相互作用作为一个潜在的机制介导性二态性。具体来说，在一项药理学行为研究中，我们计划比较OXT对男性和女性的恐惧消退和情绪识别的影响。在第二项研究中，我们将使用功能性磁共振成像来探讨OXT和雌二醇对（i）情感面部匹配任务期间杏仁核激活和（ii）人际接触时奖励相关脑激活的相互作用。我们假设外源性雌二醇的管理将提高抗焦虑和亲社会的OXT的影响。总的来说，通过揭示焦虑症性别特异性治疗的神经生物学基础和潜在机制，计划中的项目可能会产生巨大的转化影响（从实验室到床边）。雌二醇预处理后给予OXT可能有助于在未来的临床试验中提高OXT的治疗效果。

Anxiety disorders are among the most common mental illnesses and a substantial percentage of patients do not benefit from established therapeutic approaches. The neuropeptide oxytocin (OXT) has anxiolytic and prosocial properties and may thus be used as an adjunct to augment existing therapies. However, both the prevalence rates of anxiety disorders and the social effects of OXT substantially vary between women and men. The present project was therefore designed to examine gender-specific effects of OXT in healthy participants and to probe interactions between OXT and the sex steroid estradiol as a potential mechanism mediating sexual dimorphisms. Specifically, in a pharmacological behavioral study, we plan to compare OXT effects on fear extinction and emotion recognition between men and women. In a second study, we will use functional magnetic resonance imaging to explore the interplay of OXT and estradiol on (i) amygdala activation during an emotional face matching task and (ii) reward-associated brain activations in response to interpersonal touch. We hypothesize that administration of exogenous estradiol will boost the anxiolytic and prosocial effects of OXT. Collectively, by shedding light on the neurobiological basis and underlying mechanisms of gender-specific treatments for anxiety disorders, the planned project could have a large translational impact (from bench to bedside). Administration of OXT after estradiol pre-treatment might help enhance the therapeutic efficacy of OXT in future clinical trials.