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.

Specific Aim 1: To test the effects of a single-dose OT administration in adults with PTSD on
the pattern of performance on a set of laboratory tasks which have previously been
administered to similar persons who were or were not accompanied by a service canine on
separate occasions.

Hypothesis 1: Following single-dose OT administration, participants will exhibit attenuation
of attentional bias toward negatively-valenced content, in general, and toward facial cues
denoting social threat, in particular.

Hypothesis 2: Following single-dose OT administration, participants will exhibit reduced
cardioacceleratory responses to loud tones and attenuated autonomic responses to a math
stressor.

Preliminary power calculations indicate that a sample of 40 subjects in this within-subjects
design will yield excellent power to detect a medium size effect (Critical t(38) = 2.02, α =
.05, 1- β = .90) for the primary attentional bias measures.

Inclusion Criteria:

- US military Veteran

- Current posttraumatic stress disorder

- Medically healthy

Exclusion Criteria:

- DSM-5 diagnosis of schizophrenia, schizoaffective disorder, or psychotic disorder

- Active drug or alcohol use disorder within past 90 days

- Currently participating in a clinical drug trial

- Regular nasal obstruction or nosebleeds (use of saline or nasal decongestant permitted
if subject has transient cold only)

- Active medical problems: unstable seizures, significant physical illness (e.g.,
serious liver, renal, or cardiac pathology)

- Sensitivity to preservatives, in particular E 216, E 218, and chlorobutanol
hemihydrate

- Significant hearing or vision impairments

- Habitually drinks large volumes of water