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



PTSD is an extremely impairing disorder with few early preventative interventions. Intranasal oxytocin may be promising as oxytocin has been shown to positively affect socio-emotional vulnerability and neurobiological factors implicated in PTSD. The authors used an fMRI to examine the immediate effects of oxytocin administration on brain circuitry involved in fear response. They also conducted trials of repeated oxytocin administration to recently traumatized individuals to assess its efficacy in preventing the onset of PTSD. fMRI experiments revealed immediately increased activity in the amygdala to fearful faces and reduced functional connectivity at the amygdala-ventromedial and ventrolateral prefrontal cortex. Trials showed repeated oxytocin administration to lessen the development of PTSD symptoms in recently trauma-exposed emergency department patients.


PTSD develops in about 10% of traumatized individuals, becoming more costly and detrimental with co-occurring disorders (i.e., depression). There is still not enough evidence to support widespread use of trauma-focused psychotherapies such as CBT. A potential pharmacological route to preventing PTSD early posttrauma is to target neurobiological and socio-emotional factors of PTSD.

There is accumulating evidence that oxytocin may regulate autonomic (nervous system) stress response, reduce anxiety and amygdala reactivity, and positively affect prosocial behaviors and socio-emotional processes (managing emotions). Thus, intranasal oxytocin is hypothesized to target these associated areas of PTSD and prevent its development.



Oxytocin administration may be beneficial to stress regulation and social behavior, but the quality of its effects depends on interindividual differences and context. These differential effects may involve oxytocin administration enhancing salience processing. Enhanced salience processing denotes increased processing of contextual information that is normally noticeable (i.e., emotional facial expressions). Increased salience processing should be considered when investigating intranasal oxytocin.

Functional neuroimaging studies

A face-matching task with fearful, happy, and neutral expressions were used to assess single intranasal oxytocin administration on fear neurocircuitry. Oxytocin administration increased amygdala reactivity to fearful faces in everyone. Increased reactivity to neutral faces was only seen in women. As a result of enhanced salience processing, single oxytocin administration may enhance neural fear circuitry.

Neutral and trauma script-driven imagery were used to remind participants of trauma. The effects of oxytocin on amygdala-centered emotion and neural functional connectivity were assessed in this state. Oxytocin-treated patients had reduced amygdala-left ventrolateral prefrontal cortex (vlPFC) functional connectivity in response to the trauma script, compared to the neutral one. The oxytocin administration was accompanied by a decrease in sleep and an increase in the intensity of flashbacks. Regardless of script type, oxytocin increased amygdala-left insula functional connectivity and reduced amygdala-ventromedial prefrontal cortex (vmPFC) functional connectivity. Thus, single oxytocin administration may hinder emotion regulation in trauma-exposed individuals.

Randomized controlled clinical trial

An eight-day intranasal oxytocin treatment regimen started within 12 days posttrauma on PTSD symptoms at 1.5 months posttrauma was used to assess oxytocin efficacy in reducing symptoms of PTSD, depression, and anxiety.

Repeated intranasal oxytocin did not have any effect on PTSD, depression, and anxiety symptoms up to 6 months after trauma. The effects of oxytocin were moderated by the severity of PTSD symptoms before intervention. Oxytocin reduced PTSD symptoms only in people with high PTSD symptom severity. Thus, oxytocin is a promising preventative intervention for PTSD, especially for those with high acute symptoms.


The clinical trial was stopped part way, and the sample size for the fMRI study was small.


Repeated oxytocin administration is a novel promising approach to preventing PTSD development, especially for those with high acute symptoms. A single administration of oxytocin appeared to enhance fear neurocircuitry, which may be explained by enhanced salience processing. More research into the clinical applications and implications of oxytocin administration for PTSD are needed.