Abstract
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.
Highlights
Psychotic disorders are among the world’s leading causes of disability[1]
We have previously shown that a single acute dose of intranasal oxytocin (40 IU) modulates hippocampal perfusion[45,46,47] and increases the levels of choline in the anterior cingulate cortex of men at CHR-P48
We investigated whether heart rate (HR) or HR-HVR relates to clinical symptomatology in clinical high-risk for psychosis (CHR-P) men under placebo, or whether clinical symptomatology can predict intranasal oxytocin-induced increases on high-frequency HR variability (HF-HR variability (HRV)) in CHR-P men
Summary
Psychosis is often preceded by subtle features, allowing early detection and prevention[2]. Preventive approaches in psychosis are grounded on the detection[3], prognostic assessment[4] and treatment[5] of individuals at clinical high-risk for psychosis (CHR-P). CHR-P individuals accumulate risk factors for psychosis[6,7,8] that lead to attenuated positive psychotic symptoms[9], impaired functioning[10] and help-seeking[11]. These individuals have approximately 22% risk of developing a firstepisode psychosis over the following 3 years[12]. Novel treatments for this population are urgently needed[5]
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