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

The investigators will test whether intranasal oxytocin (24 IU vs placebo) will induce effects on attention bias and startle comparable to those the investigators have shown to be induced by the presence (vs absence) of a service dog in Veterans diagnosed with PTSD. This possibility is suggested by a 2015 study showing that urinary oxytocin levels are elevated in association with mutual gaze between dogs and their owners.

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.

Randomized double-blind crossover design, in which all participants will undergo 2 sessions, receiving either oxytocin nasal spray or placebo nasal spray in random order.

Participants randomly assigned to this arm will receive OT nasal spray (24 IU) at laboratory visit 1 and placebo nasal spray at visit 2. The order will be masked for participants and study staff.

Participants randomly assigned to this arm will receive placebo nasal spray at laboratory visit 1 and OT nasal spray (24 IU) at visit 2. The order will be masked for participants and study staff.

single-dose administration of OT nasal spray, complete computer-based tasks post-dose for approximately 1 hour

single-dose administration of placebo nasal spray, complete computer-based tasks post-dose for approximately 1 hour

Changes between oxytocin vs. placebo lab sessions in the asymmetric allocation of visual attention to one or another of a pair of visual stimuli presented simultaneously as quantified by gaze tracking

Difference between oxytocin vs. placebo lab sessions in the magnitude of pre-to-post startle stimulus change in heart rate

Difference between oxytocin vs. placebo lab sessions in the magnitude of pre-to-post startle stimulus change in AC-coupled electrodermal activity at the hand

Difference between oxytocin vs. placebo lab sessions in the magnitude of pre-to-post startle stimulus change in corrugator electromyography

Because data obtained by the investigators were exclusively from male combat veterans, and because the inclusion of female veterans presents challenges related to both variable interaction with gonadal hormones over the menstrual cycle and the need to test for pregnancy, only males will be enrolled into this protocol.

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

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