Autonomic nervous system (ANS) dysfunction (i.e., increased sympathetic and/or decreased parasympathetic activity) has been proposed to contribute to psychosis vulnerability. Yet, we still lack directed therapeutic strategies that improve ANS regulation in psychosis or at-risk states. The oxytocin system constitutes a potential therapeutic target, given its role in ANS regulation. However, whether intranasal oxytocin ameliorates autonomic regulation during emerging psychosis is currently unknown. We pooled together two datasets, one of 30 men at clinical high risk for psychosis (CHR-P), and another of 17 healthy men, who had participated in two double-blinded, placebo-controlled, randomised, crossover MRI studies with similar protocols. All participants self-administered 40 IU of intranasal oxytocin or placebo using a nasal spray. We recorded pulse plethysmography during a period of 8 min at about 1 h post dosing and estimated heart rate (HR) and high-frequency HR variability (HF-HRV), an index of cardio-parasympathetic activity. CHR-P and healthy men did not differ at resting HR or HF-HRV under placebo. We found a significant condition × treatment effect for HF-HRV, showing that intranasal oxytocin, compared with placebo, increased HF-HRV in CHR-P but not in healthy men. The main effects of treatment and condition were not significant. In this proof-of-concept study, we show that intranasal oxytocin increases cardio-parasympathetic activity in CHR-P men, highlighting its therapeutic potential to improve autonomic regulation in this clinical group. Our findings support the need for further research on the preventive and therapeutic potential of intranasal oxytocin during emerging psychosis, where we lack effective treatments.

自主神经系统（ANS）功能障碍（即增加的交感神经和/或减少的副交感神经活性）已被提议导致精神病易感性。然而，我们仍然缺乏在精神病或高危状态下改善ANS调节的定向治疗策略。鉴于其在ANS调节中的作用，催产素系统构成了潜在的治疗靶点。然而，目前尚不清楚鼻内催产素是否能改善精神病发作期间的自主神经调节。我们汇总了两个数据集，一个是30名临床上有精神病高风险的男性，另一个是17个健康的男性，他们参加了两个双盲，安慰剂对照，随机，交叉MRI研究，其方案相似。所有参与者使用鼻喷雾剂自行施用40 IU鼻内催产素或安慰剂。我们在给药后约1小时的8分钟内记录了脉冲体积描记法，并估算了心率（HR）和高频HR变异性（HF-HRV），这是心脏副交感神经活动的指标。CHR-P和健康男性在安慰剂下静息HR或HF-HRV时无差异。我们发现HF-HRV有显着的病情×治疗效果，表明与安慰剂相比，鼻内催产素增加了CHR-P的HF-HRV，但在健康男性中却没有。治疗和病情的主要影响不明显。在此概念验证研究中，我们显示鼻内催产素可增加CHR-P男性的心脏副交感神经活动，突出其在该临床组中改善自主调节的治疗潜力。