Intranasal oxytocin administration impacts the acquisition and consolidation of trauma-associated memories: a double-blind randomized placebo-controlled experimental study in healthy women

Abstract

Intrusive memories are a hallmark symptom of post-traumatic stress disorder (PTSD) and oxytocin has been implicated in the formation of intrusive memories. This study investigates how oxytocin influences the acquisition and consolidation of trauma-associated memories and whether these effects are influenced by individual neurobiological and genetic differences. In this randomized, double-blind, placebo-controlled study, 220 healthy women received either a single dose of intranasal 24IU oxytocin or a placebo before exposure to a trauma film paradigm that solicits intrusive memories. We used a “general random forest” machine learning approach to examine whether differences in the noradrenergic and hypothalamic-pituitary-adrenal axis activity, polygenic risk for psychiatric disorders, and genetic polymorphism of the oxytocin receptor influence the effect of oxytocin on the acquisition and consolidation of intrusive memories. Oxytocin induced significantly more intrusive memories than placebo did (t(188.33) = 2.12, p = 0.035, Cohen’s d = 0.30, 95% CI 0.16–0.44). As hypothesized, we found that the effect of oxytocin on intrusive memories was influenced by biological covariates, such as salivary cortisol, heart rate variability, and PTSD polygenic risk scores. The five factors that were most relevant to the oxytocin effect on intrusive memories were included in a Poisson regression, which showed that, besides oxytocin administration, higher polygenic loadings for PTSD and major depressive disorder were directly associated with a higher number of reported intrusions after exposure to the trauma film stressor. These results suggest that intranasal oxytocin amplifies the acquisition and consolidation of intrusive memories and that this effect is modulated by neurobiological and genetic factors. Trial registration: NCT03031405.

Oxytocin vs. placebo effects on intrusive memory consolidation using a trauma film paradigm: a randomized, controlled experimental study in healthy women

“…In contrast to the current results, we found a signi cantly increased number of intrusive memories when oxytocin was administered before an analogue trauma (during acquisition) in a previous study [12]. Accordingly, the effect of oxytocin on intrusions seems to be time depended.…”

“…In contrast, it may also enhance the salience of negative cues, resulting in anxiety and elevated stress levels in a social context that is interpreted as unpredictable or threatening [29]. Consistent with the social salience hypothesis [29], intranasal oxytocin administration before a trauma lm caused an increase in intrusive memories, in a previously conducted study [12]. However, these results do not allow conclusions on whether oxytocin impacted the acquisition or the consolidation of the trauma lm.…”

“…Biomarkers that have been shown to in uence the development of PTSD are cortisol, salivary α-amylase (sAA), and heart rate variability (HRV) [8][9][10][11][12]. Furthermore, genetic factors have been identi ed as risk factors for PTSD [13,14].…”

“…To address the complexity of PTSD development, we included a variety of predictors in the analysis using Machine Learning (ML) approaches. All included predictors have previously been associated with PTSD risk and consisted of psychological, genetic, and neurobiological variables [8, 12,13,[46][47][48]. ML approaches provide the possibility to investigate a variety of variables and their complex interactions [49].…”

“…ML approaches provide the possibility to investigate a variety of variables and their complex interactions [49]. Using ML approaches, it has been possible to identify biomarkers and multiple polygenic risk scores associated with posttraumatic stress [12,[50][51][52].…”