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

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.


Eligibility Criteria:
Inclusion Criteria

1. Ages 18-60.
2. Subjects scoring moderate to severe (\>3) on a minimum of one of the five trauma domains of the Childhood Trauma Questionnaire.
3. 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

1. Subjects with evidence of or a history of head trauma, neurological disorders, seizures, unconsciousness or any other major medical disorder.
2. Subjects with current (past 90 days) psychotic disorder or bipolar affective disorder.
3. Subjects with any psychoactive substance abuse within the last 30 days as evidenced by subject report or urine drug screen.
4. Women who are pregnant or nursing.
5. Women who are post-menopausal or have had a full hysterectomy.
6. Subjects who have a BMI greater than 35.
7. 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.
8. Persons with ferrous metal implants or pacemaker.
9. Subjects who are claustrophobic.
10. Subjects taking endocrine or cardiovascular medications (other than blood pressure medications) during the 30-day period prior to the study.
11. 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

1. As above.
2. 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).