Introduction: Anxiety disorders are prevalent mental conditions characterized by exaggerated anxious arousal and threat reactivity. Animal and human studies suggest an anxiolytic potential of the neuropeptide oxytocin (OT), yet, while a clinical application will require chronic administration protocols, previous human studies have exclusively focused on single-dose (acute) intranasal OT effects. Objective: To facilitate the translation of the potential anxiolytic mechanism of OT into clinical application, we determined whether the anxiolytic effects of OT are maintained with repeated (chronic) administration or are influenced by dose frequency and trait anxiety. Methods: In a pre-registered double-blind randomized placebo-controlled pharmaco-fMRI trial the acute (single dose) as well as chronic effects of two different dose frequencies of OT (OT administered daily for 5 days or every other day) on emotional reactivity were assessed in n = 147 individuals with high versus low trait anxiety (ClinicalTrials.gov ID: NCT03085654). Results: OT produced valence, dose frequency, and trait anxiety-specific effects, such that the low-frequency (intermittent) chronic dosage specifically attenuated a neural reactivity increase in amygdala-insula-prefrontal circuits observed in the high anxious placebo-treated subjects in response to threatening but not positive stimuli. Conclusions: The present trial provides the first evidence that low-dose frequency chronic intranasal OT has the potential to alleviate exaggerated neural threat reactivity in subjects with elevated anxiety levels, suggesting a treatment potential for anxiety disorders.
Psychother Psychosom

中文翻译：

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慢性鼻内催产素对威胁的神经反应的抗焦虑作用是剂量频率依赖性的

简介：焦虑症是一种普遍存在的精神疾病，其特征是过度的焦虑唤醒和威胁反应。动物和人体研究表明神经肽催产素 (OT) 具有抗焦虑潜力，然而，虽然临床应用需要长期给药方案，但以前的人体研究仅关注单剂量（急性）鼻内 OT 效应。目的：为了促进将 OT 的潜在抗焦虑机制转化为临床应用，我们确定了 OT 的抗焦虑作用是通过重复（慢性）给药维持还是受给药频率和特质焦虑的影响。方法：在一项预先注册的双盲随机安慰剂对照药物 fMRI 试验中，两种不同剂量频率的 OT（每天给予 5 天或每隔一天给予 OT）对情绪反应的急性（单剂量）和慢性影响分别为在n = 147 名具有高与低特质焦虑的个体中进行评估（ClinicalTrials.gov ID：NCT03085654）。结果： OT 产生效价、剂量频率和特质焦虑特异性效应，因此低频（间歇性）慢性剂量特别减弱了在高度焦虑的安慰剂治疗受试者中观察到的杏仁核-岛叶-前额叶回路的神经反应性增加。对威胁但不是积极刺激的反应。结论：目前的试验提供了第一个证据，表明低剂量频率的慢性鼻内 OT 有可能减轻焦虑水平升高的受试者的过度神经威胁反应，表明治疗焦虑症的潜力。
心理治疗师