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

2014-08-27 03:54:54 | BioPortfolio


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.


Posttraumatic stress disorder (PTSD) is characterized by intrusive recollections, avoidant behavior, anxiety and exaggerated fear response. The pathophysiology of PTSD is largely unknown. Neurophysiological testing in PTSD reveals deficits in memory and attention. Neuroimaging studies report increased amygdala and decreased anterior cingulate activation and reduced hippocampal volume. Clinical observations, psychophysiological measures and animal studies suggest that facilitated fear conditioning, delayed extinction, inescapable shock, sensitization and protracted habituation may contribute to the onset and persistence of PTSD.

We propose to use fMRI and the psychophysiology lab to examine the effect of treatment with paroxetine and cognitive behavioral therapy on regional cerebral blood flow (rCBF) in brain regions conceivably involved in evolution and maintenance of PTSD: Amygdala, anterior cingulate and hippocampus. We will use emotional tasks that have elicited differences in perfusion or metabolism between patients with PTSD and trauma exposed and healthy subjects. Tasks performed in the fMRI will include 'masked' and 'unmasked' emotional faces paradigms and differential delay conditioning. Contextual fear provocation and eyeblink trace conditioning will be done in the psychophysiology lab. This evaluation will be performed before and after a 10-week period of treatment with paroxetine and a 10-session course of cognitive behavioral treatment (CBT).

Study population will comprise the following matched groups: Patients with PTSD; previously traumatized healthy subjects who have not suffered from PTSD and non-traumatized healthy subjects. Subjects from the 1st group will either be treated with paroxetine for 10 weeks, undergo a 10-week 'prolonged exposure' (PE) CBT course, or will be put on the 'waiting list'. It is assumed that variability in outcome will be observed in both treatment modes, which will enable us to seek treatment response predictors.

It is unknown whether cerebral abnormalities in PTSD are state or trait phenomena. In depression and OCD, functional imaging research shows improvement in malfunctioning brain regions after clinically effective psychopharmacological and psychotherapeutic interventions and after administration of placebo in depression. An increase in hippocampal volume was found in patients with PTSD after treatment with paroxetine and after correction of the endocrine abnormality in Cushing's disorder. These findings support our expectation that at least some brain abnormalities in PTSD are state related, and that change in these abnormalities is demonstrable by fMRI.

Study Design



Stress Disorders, Post-Traumatic


National Institute of Mental Health (NIMH)
United States




National Institutes of Health Clinical Center (CC)

Results (where available)

View Results


Published on BioPortfolio: 2014-08-27T03:54:54-0400

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Medical and Biotech [MESH] Definitions

A class of traumatic stress disorders that is characterized by the significant dissociative states seen immediately after overwhelming trauma. By definition it cannot last longer than 1 month, if it persists, a diagnosis of post-traumatic stress disorder (STRESS DISORDERS, POST-TRAUMATIC) is more appropriate.

A class of traumatic stress disorders with symptoms that last more than one month. There are various forms of post-traumatic stress disorder, depending on the time of onset and the duration of these stress symptoms. In the acute form, the duration of the symptoms is between 1 to 3 months. In the chronic form, symptoms last more than 3 months. With delayed onset, symptoms develop more than 6 months after the traumatic event.

Anxiety disorders manifested by the development of characteristic symptoms following a psychologically traumatic event that is outside the normal range of usual human experience. Symptoms include re-experiencing the traumatic event, increased arousal, and numbing of responsiveness to or reduced involvement with the external world. Traumatic stress disorders can be further classified by the time of onset and the duration of these symptoms.

Syndromes which feature DYSKINESIAS as a cardinal manifestation of the disease process. Included in this category are degenerative, hereditary, post-infectious, medication-induced, post-inflammatory, and post-traumatic conditions.

Dyssomnias (i.e., insomnias or hypersomnias) associated with dysfunction of internal sleep mechanisms or secondary to a sleep-related medical disorder (e.g., sleep apnea, post-traumatic sleep disorders, etc.). (From Thorpy, Sleep Disorders Medicine, 1994, p187)

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