Abstract

Rationale

Arginine vasopressin (AVP) has dose- and sex-specific effects on social behavior, and variation in social responses is related to variation in the V1a receptor gene in animals. Whether such complexity also characterizes AVP effects on anxiety in humans, or whether V1a genotype is related to anxiety and/or AVP’s ability to affect it, remains to be determined.

Objective

To test if AVP has dose-dependent effects on anxiety in men and/or women and if a particular allele within the RS3 promoter region of the V1a receptor gene is associated with anxiety and/or AVP effects on anxiety.

Method

Men and women self-administered 20 IU or 40 IU intranasal arginine vasopressin (AVP) and placebo in a double-blind, within-subjects design, and State (SA) and Trait (TA) anxiety were measured 60 min later. PCR was used to identify allelic variation within the RS3 region of the V1a receptor gene.

Results

AVP decreased SA in men across both doses, whereas only the lower dose had the same effect, across sexes, in individuals who carry at least one copy of a previously identified “risk” allele in the RS3 promoter of the V1a receptor gene. Additionally, after placebo, women who carried a copy of the allele displayed lower TA than women who did not, and AVP acutely increased TA scores in those women.

Conclusions

Exogenous AVP has modest sex- and dose-dependent effects on anxiety/affect in humans. Further, allelic variation in the V1a promoter appears associated with responsiveness to AVP’s effects and, at least in women, to stable levels of anxiety/affect.

中文翻译：

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精氨酸加压素对人类焦虑的影响及其与性别、剂量和 V1a 受体基因型的关系

摘要

基本原理

精氨酸加压素 (AVP) 对社会行为具有剂量和性别特异性的影响，而社会反应的变化与动物 V1a 受体基因的变化有关。这种复杂性是否也是 AVP 对人类焦虑影响的特征，或者 V1a 基因型是否与焦虑和/或 AVP 影响焦虑的能力有关，仍有待确定。

客观的

测试 AVP 对男性和/或女性焦虑是否具有剂量依赖性影响，以及 V1a 受体基因 RS3 启动子区域内的特定等位基因是否与焦虑和/或 AVP 对焦虑的影响相关。

方法

男性和女性以双盲、受试者内设计的方式自行注射 20 IU 或 40 IU 鼻内精氨酸加压素 (AVP) 和安慰剂，并在 60 分钟后测量状态 (SA) 和特质 (TA) 焦虑。 PCR 用于鉴定 V1a 受体基因 RS3 区域内的等位基因变异。

结果

两种剂量的 AVP 均可降低男性的 SA，而对于不同性别的 V1a 受体基因 RS3 启动子中携带至少一个先前识别的“风险”等位基因拷贝的个体，只有较低剂量的 SA 具有相同的效果。此外，服用安慰剂后，携带等位基因副本的女性表现出比不携带等位基因副本的女性更低的 TA，而 AVP 急剧增加了这些女性的 TA 分数。

结论

外源性 AVP 对人类焦虑/情感具有适度的性别和剂量依赖性影响。此外，V1a 启动子中的等位基因变异似乎与 AVP 效应的反应有关，并且至少在女性中与稳定的焦虑/情感水平有关。