Brain Structure and Function Before and After Treatment for Post-Traumatic Stress Disorder

This study, conducted at the University of Pennsylvania and at the National Institutes of Health in Bethesda, Maryland, will examine deficits in brain structure and function in people exposed to trauma who developed post-traumatic stress disorder (PTSD) to see if these deficits change after treatment. It also will investigate whether there is a genetic susceptibility to PTSD. Candidates 18 years of age and older in the following categories will be included in this study: 1) women who have PTSD of at least 1 year's duration following sexual or non-sexual assault; 2) healthy women (controls) who were previously assaulted but did not develop PTSD; and 3) healthy women (controls) who were never traumatized. Candidates will be screened with a medical history and physical examination, psychiatric evaluation, electrocardiogram (EKG), and routine blood and urine tests. Women with PTSD will be assigned to receive either: 1) 12 weeks of cognitive behavioral psychotherapy either immediately upon enrollment or after a 3-month waiting period; or 2) 10 weeks of drug treatment with paroxetine (Paxil® (Registered Trademark)). Patients will be evaluated before and after treatment with the procedures outlined below. Control subjects will undergo the same procedures, also with a 10- to 12-week interval between evaluations.

• Neuropsychological testing: Subjects will take paper and pencil and computer tests to evaluate memory, learning, attention and concentration, vocabulary and naming.
• Magnetic resonance imaging (MRI): Subjects will have MRI scans of the brain to examine brain structure and blood flow while they perform two tasks. In the first task, they will be shown a series of faces and asked to press one button for a male face and another button for a female face. In the second task they will hear loud noises and see colored squares. During the scan, subjects lie on a bed that slides into a narrow tunnel (the scanner). They will wear a headset to block the noise of the scanner and through which they will receive instructions for the tasks. Heart rate and skin conductance (sweating) will be measured during the scan to evaluate physiologic changes in response to the tasks.
• Eyeblink air puff test: Subjects will hear tones and will have a light puff of air delivered to the eye. Changes in heart rate, sweat, and eyeblink will be measured with electrodes taped to the skin on two fingers, on each side of the rib cage, and under one eye.
• Potential air puff delivery: This experiment has three parts. During each of the three parts of this experiment, subjects will see colored lights and may or may not receive a puff of air to the neck. Before each part they will be told that they will, will not, or may receive an air puff to the neck. Each part will be repeated several times. During the test, electrodes will be taped to the arms and chest to monitor skin conductance and heart rate responses.
• Blood draw for genetic evaluation: Subjects' DNA will be examined to try to determine if the risk of developing PTSD is inherited. The DNA will be examined for cortisol receptor gene evaluation, to see if a form of this gene is found more often in patients with PTSD than in healthy controls. The receptor for cortisol determines the activity of the stress hormone cortisol, and genetic variations in the structure of this receptor may be related to vulnerability to PTSD. Patients taking paroxetine will be offered up to 3 months of additional drug therapy following completion of the study and will be offered participation in other NIH studies for evaluation and treatment of PTSD.