Study of the Effects of Oxytocin on Attentional Bias and Startle in PTSD
Condition: Posttraumatic Stress Disorder
MeSH terms: Stress Disorders, Post-Traumatic
Study type: Interventional
Phase: Early Phase 1

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Oxytocin; Placebos
Intervention type(s): Drug; Drug
Intervention description(s): 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
Other intervention name(s): syntocinon
Intervention MeSH terms: Oxytocin
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: 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.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: oxytocin; PTSD; attention bias; startle