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.