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，相当大比例的患者没有从既定的治疗方法中受益。神经肽催产素(OXT)具有抗焦虑和亲社会的特性，因此可用作现有疗法的辅助药物。然而，焦虑症的患病率和OXT的社会影响在女性和男性之间都有很大差异。因此，本项目旨在研究OXT在健康参与者中的性别特异性影响，并探索OXT与性类固醇雌二醇之间的相互作用，以此作为调停性二型性的潜在机制。具体地说，在一项药理学行为研究中，我们计划比较OXT在消除男性和女性之间的恐惧和情绪识别方面的效果。在第二项研究中，我们将使用功能磁共振成像来探索OXT和雌二醇在(I)情绪面孔匹配任务中杏仁核激活和(Ii)人际触摸反应中与奖励相关的大脑激活上的相互作用。我们假设外源性雌二醇会增强OXT的抗焦虑和亲社会作用。总而言之，通过揭示焦虑症针对性别的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翻译影响(从长凳到床边)。在未来的临床试验中，在雌二醇预处理后给予OXT可能有助于提高OXT的疗效。

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.