Oxytocin and Affect Processing in Posttraumatic Stress Disorder

Posttraumatic Stress Disorder and Affective Functioning: A Test of the Potentially Normalizing Effects of Oxytocin

The investigators will use multiple methods (including Oxytocin intranasal inhalation, neuroimaging, behavioral measures, peripheral hormone measurements) to examine how individuals' behavior, cognition, and brain function is impacted by the neuro-hormone Oxytocin. Specifically, the investigators plan to evaluate the influence of Oxytocin administration on affective processing in non-trauma exposed and trauma-exposed adults (both with and without posttraumatic stress disorder, PTSD).

Study Overview

• Status: Completed
• Conditions: Posttraumatic Stress Disorder (PTSD)
• Intervention / Treatment: Drug: Oxytocin; Drug: Placebo

Detailed Description

The investigators will use multiple methods (including Oxytocin intranasal inhalation, neuroimaging, behavioral measures, peripheral hormone measurements) to examine how individuals' behavior, cognition, and brain function is impacted by the neuro-hormone Oxytocin. Specifically, the investigators plan to evaluate the influence of Oxytocin administration on affective processing in non-trauma exposed and trauma-exposed adults (both with and without posttraumatic stress disorder, PTSD). The investigators expect oxytocin (compared to placebo) to positively influence affect processing in healthy subjects, as well as among those diagnosed with PTSD. Given current literature, the investigators expect oxytocin to elevate the processing\perception of positive-related stimuli, and reduce the salience of aversive or un-pleasant cues. The investigators expect oxytocin to impact participants' brain function as measured with functional magnetic resonance imaging (fMRI) while visually processing social and affect-related stimuli, rendering brain function and affective processing to be "more typical" or "adaptive" compared to placebo. Oxytocin's effect on human repertoire is not necessarily direct, but can interact with the individual's socioemotional characteristics, early life environment, and psychiatric symptoms. Therefore, the investigators will incorporate measures that capture the various dimensions that likely shape the effect of oxytocin.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults: age 18-55
• Be in good medical health
• Be cooperative with testing
• English is a language spoken in the family
• PTSD as diagnosed by a certified clinician or the research team for PTSD group.

Exclusion Criteria:

• Moderate or severe acute or chronic medical illnesses (e.g.cardiac disease, diabetes, epilepsy, influenza).
• History of hypertension with baseline blood pressure above 160 mm Hg (systolic) over 100 mm Hg (diastolic).
• history of syncope and/or baseline blood pressure below 100 mm Hg (systolic).
• weight >300lb
• The use of some psychotropic medications will not be allowed. Females taking contraceptive hormones will not be able to participate in the study.
• Currently breast feeding or pregnant
• For MRI ONLY: Any metal or electromagnetic implants
• For MRI ONLY: Significant hearing loss or other severe sensory impairment
• A fragile health status.
• For MRI ONLY: A history of seizures or current use of anticonvulsants
• Healthy adult controls (HC):
• Be free of both neurological and psychiatric disorders (current and past) on the basis of self-report
• Be free of psychiatric disorders

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy adult controls (18-55); Drug: oxytocin and placebo nasal spray (within-subjects design, blinded and counterbalanced for two lab sessions); dosage=24 international units (IU). Participant inserts nasal spray container 1cm into nostril at angle of 45 degrees and sprays. Will wait 15 seconds then repeat administration to other nostril (alternating between nostrils). Participants will receive 6 puffs in total (3 in each nostril).	Drug: Oxytocin; See arm/group descriptions for dosage amount and procedure.; Other Names: Pitocin; Drug: Placebo; See arm/group descriptions for dosage amount and procedure.; Other Names: saline
Experimental: Adults with PTSD (18-55); Drug: oxytocin and placebo nasal spray (within-subjects design, blinded and counterbalanced for two lab sessions); dosage=24 international units (IU). Participant inserts nasal spray container 1cm into nostril at angle of 45 degrees and sprays. Will wait 15 seconds then repeat administration to other nostril (alternating between nostrils). Participants will receive 6 puffs in total (3 in each nostril).	Drug: Oxytocin; See arm/group descriptions for dosage amount and procedure.; Other Names: Pitocin; Drug: Placebo; See arm/group descriptions for dosage amount and procedure.; Other Names: saline
Experimental: Trauma-exposed/no-PTSD adults (18-55); Drug: oxytocin and placebo nasal spray (within-subjects design, blinded and counterbalanced for two lab sessions); dosage=24 international units (IU). Participant inserts nasal spray container 1cm into nostril at angle of 45 degrees and sprays. Will wait 15 seconds then repeat administration to other nostril (alternating between nostrils). Participants will receive 6 puffs in total (3 in each nostril).	Drug: Oxytocin; See arm/group descriptions for dosage amount and procedure.; Other Names: Pitocin; Drug: Placebo; See arm/group descriptions for dosage amount and procedure.; Other Names: saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
fMRI Analysis: Change in Anterior Insula Region	Change in blood-oxygen-level dependent (BOLD) contrast signal in regions of interest relevant to fear/threat (e.g., decrease in amygdala activation) and reward processing (increase in ventral striatum activation) in oxytocin versus placebo sessions. Forearm brush stroking targets C-tactile (CT) nerves, which respond to gentle touch and engage the insula and cortical brain regions that mediate social-emotional processing. Palm brush stroking is the control condition, in that CT afferents do not innervate the palm. We contrasted BOLD responses to gentle continuous brushing of the arm vs. palm (4 blocks of 8 trials each), expecting greater oxytocin-related increases in brain reactivity within the insula and other regions in the forearm condition versus the palm condition. The values are % signal change from baseline.	1 week; fMRI data collected at second and third visits, one week apart
fMRI Analysis: Change in Accumbens Region	Change in blood-oxygen-level dependent (BOLD) contrast signal in regions of interest relevant to fear/threat (e.g., decrease in amygdala activation) and reward processing (increase in ventral striatum activation) in oxytocin versus placebo sessions. Forearm brush stroking targets C-tactile (CT) nerves, which respond to gentle touch and engage the insula and cortical brain regions that mediate social-emotional processing. Palm brush stroking is the control condition, in that CT afferents do not innervate the palm. We contrasted BOLD responses to gentle continuous brushing of the arm vs. palm (4 blocks of 8 trials each), expecting greater oxytocin-related increases in brain reactivity within the insula and other regions in the forearm condition versus the palm condition. The values are % signal change from baseline.	1 week; fMRI data collected at second and third visits, one week apart
fMRI Analysis: Change in Amygdala Region	Change in blood-oxygen-level dependent (BOLD) contrast signal in regions of interest relevant to fear/threat (e.g., decrease in amygdala activation) and reward processing (increase in ventral striatum activation) in oxytocin versus placebo sessions. Forearm brush stroking targets C-tactile (CT) nerves, which respond to gentle touch and engage the insula and cortical brain regions that mediate social-emotional processing. Palm brush stroking is the control condition, in that CT afferents do not innervate the palm. We contrasted BOLD responses to gentle continuous brushing of the arm vs. palm (4 blocks of 8 trials each), expecting greater oxytocin-related increases in brain reactivity within the insula and other regions in the forearm condition versus the palm condition. The values are % signal change from baseline.	1 week; fMRI data collected at second and third visits, one week apart
fMRI Analysis: Change in dACC Region	Change in blood-oxygen-level dependent (BOLD) contrast signal in regions of interest relevant to fear/threat (e.g., decrease in amygdala activation) and reward processing (increase in ventral striatum activation) in oxytocin versus placebo sessions. Forearm brush stroking targets C-tactile (CT) nerves, which respond to gentle touch and engage the insula and cortical brain regions that mediate social-emotional processing. Palm brush stroking is the control condition, in that CT afferents do not innervate the palm. We contrasted BOLD responses to gentle continuous brushing of the arm vs. palm (4 blocks of 8 trials each), expecting greater oxytocin-related increases in brain reactivity within the insula and other regions in the forearm condition versus the palm condition. The values are % signal change from baseline.	1 week; fMRI data collected at second and third visits, one week apart
fMRI Analysis: Change in mOFC Region	Change in blood-oxygen-level dependent (BOLD) contrast signal in regions of interest relevant to fear/threat (e.g., decrease in amygdala activation) and reward processing (increase in ventral striatum activation) in oxytocin versus placebo sessions. Forearm brush stroking targets C-tactile (CT) nerves, which respond to gentle touch and engage the insula and cortical brain regions that mediate social-emotional processing. Palm brush stroking is the control condition, in that CT afferents do not innervate the palm. We contrasted BOLD responses to gentle continuous brushing of the arm vs. palm (4 blocks of 8 trials each), expecting greater oxytocin-related increases in brain reactivity within the insula and other regions in the forearm condition versus the palm condition. The values are % signal change from baseline.	1 week; fMRI data collected at second and third visits, one week apart
fMRI Analysis: Change in rACC Region	Change in blood-oxygen-level dependent (BOLD) contrast signal in regions of interest relevant to fear/threat (e.g., decrease in amygdala activation) and reward processing (increase in ventral striatum activation) in oxytocin versus placebo sessions. Forearm brush stroking targets C-tactile (CT) nerves, which respond to gentle touch and engage the insula and cortical brain regions that mediate social-emotional processing. Palm brush stroking is the control condition, in that CT afferents do not innervate the palm. We contrasted BOLD responses to gentle continuous brushing of the arm vs. palm (4 blocks of 8 trials each), expecting greater oxytocin-related increases in brain reactivity within the insula and other regions in the forearm condition versus the palm condition. The values are % signal change from baseline.	1 week; fMRI data collected at second and third visits, one week apart
fMRI Analysis: Change in vmPFC Region	Change in blood-oxygen-level dependent (BOLD) contrast signal in regions of interest relevant to fear/threat (e.g., decrease in amygdala activation) and reward processing (increase in ventral striatum activation) in oxytocin versus placebo sessions. Forearm brush stroking targets C-tactile (CT) nerves, which respond to gentle touch and engage the insula and cortical brain regions that mediate social-emotional processing. Palm brush stroking is the control condition, in that CT afferents do not innervate the palm. We contrasted BOLD responses to gentle continuous brushing of the arm vs. palm (4 blocks of 8 trials each), expecting greater oxytocin-related increases in brain reactivity within the insula and other regions in the forearm condition versus the palm condition. The values are % signal change from baseline.	1 week; fMRI data collected at second and third visits, one week apart

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Salivary Oxytocin	Expect within-session (30 min) increase in peripheral salivary oxytocin level during OT sessions (within-session), and higher OT levels in oxytocin administration vs. placebo sessions. Peripheral OT levels measured with Salivettes (sterile cotton participants will be asked to chew on for 1 minutes).	Within session (30 min) and between sessions (1 week); saliva samples collected twice (before and after OT administration) at both second and third visits, one week apart

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Center for PTSD
• Investigators: Principal Investigator: Linda Mayes, MD, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2015
• Primary Completion (Actual): August 1, 2016
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: June 15, 2015
• First Submitted That Met QC Criteria: September 8, 2015
• First Posted (Estimate): September 11, 2015

Study Record Updates

• Last Update Posted (Actual): April 8, 2020
• Last Update Submitted That Met QC Criteria: March 16, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Trauma and Stressor Related Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Oxytocin
• Other Study ID Numbers: 1502015347

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided