Placebo-Controlled Study of the Effects of Oxytocin on Attentional Bias and Startle in PTSD

Background and significance:

Chronic severe posttraumatic stress disorder (PTSD) is among the most prevalent and expensive diagnoses addressed by the U.S. Army Medical Department and the Veterans Health Administration. While progress has been made in PTSD treatment, data from the World Mental Health Survey have recently shown that rates of recovery from combat-related PTSD, world-wide, are approximately one-half the rates of recovery from other trauma types. Furthermore, other recent studies have reported that effect sizes shown by evidence-based treatments for PTSD when applied to male patients are approximately half of what they are when applied to female patients. These results suggest the VA has far to go in achieving efficacious and effective behavioral treatments for this diagnosis affecting a large proportion of its patient population.

In the course of a DoD-funded study (Can a Canine Companion Modify Cardiac Autonomic Reactivity and Tone in PTSD) our laboratory has found that the presence of a service canine in the testing chamber in close proximity to the participant is associated with modification of visual attentional bias away from angry faces signalling social threat along with attenuation of autonomic responses to loud tones. The attenuation of bias towards social threat is of particular relevance to the social impairments seen in this disorder.Veterans with chronic severe PTSD frequently manifest impairments in the execution of key social roles such as those of spouse, parent and employee.

Service canine companionship and oxytocin (OT) appear to be on parallel tracks as novel candidate PTSD treatments or treatment enhancers. A wealth of anecdotal evidence has emerged from U.S. military clinical settings supporting the benefits of service canine companionship and canine-assisted interventions for military personnel with deployment-related mental health conditions; however, rigorously empirical support for this approach remains sparse. A growing literature exploring the role(s) of the OT system in PTSD now includes a number of encouraging findings. For example, in PTSD, OT modulates amygdala hemodynamic responses to emotional faces and increases anterior insula hemodynamic responses to social rewards. Intranasal OT administration normalizes amygdala functional connectivity in PTSD and increased subjective compassion for other persons. These findings align with findings in healthy persons. After intranasal administration, normal adults gaze more at the eye region of faces, have better memory for faces, are better able to infer the mental states of others, have more positive communications, are more generous, rate faces as more trustworthy owe, and exhibit increased trust behavior. OT also attenuates startle in healthy persons, attenuates amygdala responses to fear-inducing stimuli, and inhibits the stress-responsive release of cortisol. In turn, the human findings generally agree with a large animal literature showing that OT plays an important role in social behaviors such as partner preference, social bonding, and social cognition, while OT dysregulation produces a variety of social impairments.

A recent study published in Science showing that urinary OT levels are elevated in association with mutual gaze between dogs and their owners suggests these two lines of research may be converged on the target of PTSD. The investigators will compare the pattern of results of tests of attention bias and startle induced by intranasal OT (vs placebo) to those the investigators have shown to be induced by the presence (vs absence) of a service dog in Veterans diagnosed with PTSD.