Fear-extinction based psychotherapy (exposure) is the most effective method for treating anxiety disorders. Notwithstanding, since some patients show impairments in the unlearning of fear and insufficient fear remission, there is a growing interest in using cognitive enhancers as adjuvants to exposure. As insulin plays a critical role in stress processes and acts as a memory enhancer, this study aimed to assess the capacity of intranasal insulin to augment fear extinction. A double-blind, placebo-controlled differential fear-conditioning paradigm was conducted in 123 healthy participants (63 females). Pictures of faces with neutral expressions were used as conditioned stimuli and electric shocks as unconditioned stimuli. The paradigm consisted of four phases presented on three consecutive days: acquisition (day 1), extinction (day 2), reinstatement and re-extinction (day 3). A single intranasal dose of insulin (160 IU) or placebo was applied on day 2, 45 min before fear extinction. Skin conductance response (SCR), fear-potentiated startle (FPS) and expectancy ratings were assessed. During extinction, the insulin group (independent of sex) showed a significantly stronger decrease in differential FPS in comparison with the placebo group. Furthermore, a sex-specific effect was found for SCR, with women in the insulin group showing a greater decrease of differential SCR both at early extinction and at late re-extinction. Our results provide first evidence that intranasal insulin facilitates fear extinction processes and is therefore a promising adjuvant for extinction-based therapies in anxiety and related disorders. Sex-specific effects should be taken into consideration in future studies.

中文翻译：

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鼻内胰岛素作为恐惧消除的增强剂的作用：一项随机，双盲，安慰剂对照的实验研究。

基于恐惧消灭的心理治疗（暴露）是治疗焦虑症最有效的方法。尽管如此，由于一些患者在恐惧的学习和恐惧缓解方面显示出障碍，因此越来越有兴趣使用认知增强剂作为暴露的佐剂。由于胰岛素在应激过程中起着关键作用，并起着记忆增强的作用，因此本研究旨在评估鼻内胰岛素增强恐惧消退的能力。在123名健康参与者（63名女性）中进行了双盲，安慰剂对照的差异恐惧调节范例。具有中性表情的面部图片被用作条件刺激，电击被用作非条件刺激。该范式由连续三个天呈现的四个阶段组成：获取（第1天），灭绝（第2天），恢复和灭绝（第3天）。恐惧消失前的第2天，第45分钟使用鼻内单剂量胰岛素（160 IU）或安慰剂。评估了皮肤电导反应（SCR），恐惧增强的惊吓（FPS）和预期等级。在绝种期间，与安慰剂组相比，胰岛素组（不分性别）的差异性FPS下降明显更强。此外，发现对SCR具有性别特异性作用，胰岛素组的女性在早期灭绝和晚期灭绝时均表现出差异性SCR的更大降低。我们的结果提供了第一个证据，即鼻内胰岛素促进了恐惧的消退过程，因此是焦虑和相关疾病中基于消光疗法的有前途的佐剂。