Oxytocin and Affect Processing in Posttraumatic Stress Disorder

Phase 2

Completed

Conditions: Posttraumatic Stress Disorder (PTSD)

Interventions: Drug: Oxytocin
Drug: Placebo

Registration Number: NCT02546570

Lead Sponsor: Yale University

Brief Summary: 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).

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 11

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Adults with PTSD (18-55)	Placebo	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).
Trauma-exposed/no-PTSD adults (18-55)	Placebo	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).
Healthy adult controls (18-55)	Placebo	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).
Healthy adult controls (18-55)	Oxytocin	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).
Adults with PTSD (18-55)	Oxytocin	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).
Trauma-exposed/no-PTSD adults (18-55)	Oxytocin	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).

Primary Outcome Measures

Name	Time	Method
fMRI Analysis: Change in mOFC Region	1 week; fMRI data collected at second and third visits, one week apart	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.
fMRI Analysis: Change in rACC Region	1 week; fMRI data collected at second and third visits, one week apart	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.
fMRI Analysis: Change in Anterior Insula Region	1 week; fMRI data collected at second and third visits, one week apart	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.
fMRI Analysis: Change in Accumbens Region	1 week; fMRI data collected at second and third visits, one week apart	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.
fMRI Analysis: Change in dACC Region	1 week; fMRI data collected at second and third visits, one week apart	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.
fMRI Analysis: Change in Amygdala Region	1 week; fMRI data collected at second and third visits, one week apart	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.
fMRI Analysis: Change in vmPFC Region	1 week; fMRI data collected at second and third visits, one week apart	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.

Secondary Outcome Measures

Name	Time	Method
Salivary Oxytocin	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	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).