Sex/Gender Differences in Risk and Resilience to PTSD; Implication of Oxytocin

Study Overview
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Brief Summary
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The purpose of the study is to use fMRI to investigate amygdala response to fearful faces in men and women with and without PTSD who have experienced childhood trauma. The study will also compare the effects of oxytocin and placebo on amygdala response, and explore the interaction of oxytocin plasma levels and amygdala response in men and women with and without PTSD who have experienced childhood trauma. Hypothesis 1: Amygdala responding will be greater in subjects with PTSD as compared to resilient subjects, and no sex differences in the magnitude of the response will be found. Hypothesis 2A: In response to OT, women will exhibit a greater reduction in amygdala responding than men. Hypothesis 2B: In response to OT, women with PTSD will exhibit a greater reduction in amygdala responding compared to women without PTSD. Hypothesis 3A: Women with PTSD will have lower levels of plasma OT as compared to men with PTSD, and women and men without PTSD. Hypothesis 3B: Plasma OT levels will be inversely correlated with amygdala responding to fearful faces in women but not in men.

Official Title
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Sex/Gender Differences in Risk and Resilience to PTSD; Implication of Oxytocin

Conditions
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PTSD

Intervention / Treatment
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* Drug: Oxytocin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Ages 18-60. Subjects scoring moderate to severe (>3) on a minimum of one of the five trauma domains of the Childhood Trauma Questionnaire. Subjects must have experienced, witnessed, or confronted an event(s) that involved actual or threatened death or serious injury, or a threat to the physical integrity of themselves, or others and the person's response involved intense fear, helplessness, and/or horror (Criterion A DSM-IV for PTSD), prior to the age of 18. Exclusion Criteria Subjects with evidence of or a history of head trauma, neurological disorders, seizures, unconsciousness or any other major medical disorder. Subjects with current (past 90 days) psychotic disorder or bipolar affective disorder. Subjects with any psychoactive substance abuse within the last 30 days as evidenced by subject report or urine drug screen. Women who are pregnant or nursing. Women who are post-menopausal or have had a full hysterectomy. Subjects who have a BMI greater than 35. Subjects who are unwilling to maintain abstinence from alcohol and caffeine for the 24-hour period prior to the study visits and from illicit drug use for the 72 hour period prior to study visits. Persons with ferrous metal implants or pacemaker. Subjects who are claustrophobic. Subjects taking endocrine or cardiovascular medications (other than blood pressure medications) during the 30-day period prior to the study. Subjects with a postive breathalyzer or urine drug screen. Group - Specific Inclusion/Exclusion Criteria Individuals with PTSD Inclusion Criteria 1. Subjects must meet DSM-IV criteria for current (i.e. last 6 months) PTSD. 2. Subjects may also meet criteria for a mood disorder (except bipolar affective disorder, see Exclusion Criteria) or other anxiety disorders (panic disorder, agoraphobia, social phobia, generalized anxiety disorder, or obsessive compulsive disorder) or past (>90 days) alcohol dependence. The inclusion of subjects with affective and other anxiety disorders is essential because of the marked frequency of the co-existence of mood and other anxiety disorders among patients with PTSD (Brady, Killeen, Brewerton, & Lucerini, 2000; Kessler, Chiu, Demler, Merikangas, & Walters, 2005). Exclusion Criteria As above. Substance dependence within the past year, except for nicotine or alcohol. Resilient Controls Inclusion Criteria 1. As above. Exclusion Criteria 1. Subjects meeting criteria for current or past (i.e. last 90 days) Axis I mood or anxiety disorders (including PTSD and depression).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: PTSD placebo Day 1, Oxytocin Day 2<br>Participants PTSD will self-administer matching placebo (containing all ingredients except OT) at 10:30 a.m. on Day 1 of study procedures, approximately 45-minutes prior the scanning sessions. This dose and timing of administration were selected based on similar fMRI studies (Domes, et al., 2007; Domes, et al., 2010; Kirsch, et al., 2005). | Drug: Placebo<br> <br> * Other names: Saline;|
| Experimental: PTSD Oxytocin Day 1, Placebo Day 2<br>Participants with PTSD will self-administer 24 IUs of OT nasal spray at 10:30 a.m. on Day 1 of study procedures, approximately 45-minutes prior the scanning sessions. This dose and timing of administration were selected based on similar fMRI studies (Domes, et al., 2007; Domes, et al., 2010; Kirsch, et al., 2005). | Drug: Oxytocin<br> <br> * Other names: Pitocin;|
| Placebo Comparator: Resilient Placebo Day 1, Oxytocin Day 2<br>Resilient controls will self-administer matching placebo spray at 10:30 a.m. on Day 1 of study procedures, approximately 45-minutes prior the scanning sessions. This dose and timing of administration were selected based on similar fMRI studies (Domes, et al., 2007; Domes, et al., 2010; Kirsch, et al., 2005). | Drug: Placebo<br> <br> * Other names: Saline;|
| Experimental: Resilient Oxytocin Day 1, Placebo Day 2<br>Resilient controls will self-administer 24 IUs of OT nasal spray at 10:30 a.m.on Day 1 of study procedures, approximately 45-minutes prior the scanning sessions. This dose and timing of administration were selected based on similar fMRI studies (Domes, et al., 2007; Domes, et al., 2010; Kirsch, et al., 2005). | Drug: Oxytocin<br> <br> * Other names: Pitocin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Amygdala Activation- Oxy Minus Placebo | Bold signal response to facial recognition task was contrasted between oxytocin and saline administrations. Participants with PTSD and Resilient Controls each underwent 2 sets of scanning procedures, one with placebo and one with Oxytocin. Participants were randomly assigned to received Oxytocin on Day 1 or Day 2, and placebo on the opposite day, to mitigate crossover effects. Outcome measure is change in bold signal response between the two days; bold signal response on placebo was subtracted from bold signal response on Oxytocin to obtain change score. | Days 1 and 2 |