Preventing PTSD with oxytocin: effects of oxytocin administration on fear neurocircuitry and PTSD symptom development in recently trauma-exposed individuals

Abstract

Background: Posttraumatic stress disorder (PTSD) is a debilitating psychiatric disorder which develops in approximately 10% of trauma-exposed individuals. Currently, there are few early preventive interventions available for PTSD. Intranasal oxytocin administration early posttrauma may prevent PTSD symptom development, as oxytocin administration was previously found to beneficially impact neurobiological (e.g. amygdala reactivity) and socio-emotional PTSD vulnerability factors. Objective: The overall aim of this dissertation was to investigate the potential of intranasal oxytocin administration as early preventive intervention for PTSD. Methods: We performed a functional magnetic resonance imaging (fMRI) study to assess the acute effects of a single administration of oxytocin on the functional fear neurocircuitry – consisting of the amygdala and (pre)frontal brain regions – in recently trauma-exposed emergency department patients (range n = 37–41). In addition, we performed a multicentre randomized double-blind placebo-controlled clinical trial (RCT) to assess the efficacy of repeated intranasal oxytocin administration early after trauma for preventing PTSD symptom development up to six months posttrauma (n = 107). Results: In our fMRI experiments we observed acutely increased amygdala reactivity to fearful faces and attenuated amygdala-ventromedial and ventrolateral prefrontal cortex functional connectivity after a single oxytocin administration in recently trauma-exposed individuals. However, in our RCT we found that repeated intranasal oxytocin administration early posttrauma reduced subsequent PTSD symptom development in recently trauma-exposed emergency department patients with high acute PTSD symptoms. Conclusions: These findings indicate that repeated intranasal oxytocin is a promising early preventive intervention for PTSD for individuals at increased risk for PTSD due to high acute symptom severity. Administration frequency dependent effects of oxytocin or the effects of oxytocin administration on salience processing may serve as explanatory frameworks for the contrasting oxytocin effects on anxiety-related measures in our clinical and neuroimaging studies.

Sex and gender differences in post-traumatic stress disorder: an update

“…In PTSD patients, we showed sex-specific routes for the effects of single oxytocin administration on the potential to diminish anxiety (fear learning) and fear expression by the amygdala: increased inhibitory control of the vmPFC over the centromedial nucleus in men and fewer excitatory dorsal anterior cingulate cortex projections to the basolateral nucleus in women. So, while our findings add to accumulating evidence that oxytocin administration could potentially enhance treatment response in PTSD, the routes in men and women differ (Frijling, 2017). …”

“…We hypothesized that the oxytocin system, which is associated with social support, fear and stress responses, was likely to play a sex-specific role in the stress response. In recently traumatized patients, we found that the effects of administration of oxytocin on amygdala reactivity to emotional stimuli depend on stimulus valence and sex (Frijling, 2017). In PTSD patients, we showed sex-specific routes for the effects of single oxytocin administration on the potential to diminish anxiety (fear learning) and fear expression by the amygdala: increased inhibitory control of the vmPFC over the centromedial nucleus in men and fewer excitatory dorsal anterior cingulate cortex projections to the basolateral nucleus in women.…”

Emotional remodeling with oxytocin durably rescues trauma-induced behavioral and neuro-morphological changes in rats: a promising treatment for PTSD

“…In humans, oxytocin delivered shortly after trauma 21,22 was reported to prevent the manifestation of the PTSD symptomatology. Indeed, the temporal contiguity between trauma and treatment suggests an acute effect of oxytocin on the neural support of a partially stabilized memory.…”

A Comparison of the Ability of Leu8- and Pro8-Oxytocin to Regulate Intracellular Ca2+and Ca2+-Activated K+Channels at Human and Marmoset Oxytocin Receptors

“…OT is a fundamental mediator of sociobehavioral processes, including social cognition (Crespi, 2016), interpersonal trust (Kosfeld et al, 2005;Baumgartner et al, 2008), anxiety (Missig et al, 2010), and stress response (Light et al, 2000;Cavanaugh et al, 2016), generating interest in OT as a potential therapeutic mediator of sociobehavioral deficits in conditions such as autism spectrum disorder (Andari et al, 2010;Anagnostou et al, 2012), post-traumatic stress disorder (Frijling, 2017;Sack et al, 2017), and schizophrenia (Pedersen et al, 2011;Brambilla et al, 2016). One major challenge is connecting pharmacologic signatures to sociobehavioral processes.…”