The purpose of this study is to determine whether people who develop Post-Traumatic Stress
Disorder (PTSD) after a trauma have increased sensitivity to the effects of a stress
Patients with PTSD have small hippocampal volume and deficits in hippocampal-mediated memory
as compared to healthy people. However, it is unclear whether the smaller hippocampi are a
consequence of PTSD or a risk factor for the development of PTSD. Some researchers believe
that people who develop PTSD have an increase in cortisol levels during traumatic
experiences and that this could be neurotoxic to the hippocampus. Others hypothesize that
increased sensitivity of glucocorticoid receptors to cortisol, regardless of the cortisol
levels, could lead to neurotoxic damage to the hippocampus. This study will compare
responses to a stress hormone in patients with PTSD, participants who have experienced
trauma but do not have PTSD, and healthy volunteers.
Participants will be screened with a medical and psychiatric interview, physical
examination, blood tests, electrocardiogram, and an emotional intelligence evaluation. Those
eligible for the study will be asked to collect urine and saliva samples for 3 days.
Participation will also include blood draws, a PET scan (brain imaging), an eye-blink test,
neuropsychological testing, and other procedures.
At another study visit, participants will undergo a magnetic resonance imaging (MRI) scan
(brain imaging), questionnaires, and other procedures.
Patients with post traumatic stress disorder (PTSD) related to combat or civilian trauma
have been found to have small hippocampal volume, and deficits in hippocampal mediated
memory, compared to the controls. However, it is not clear if the smaller hippocampi are a
consequence of the extreme trauma and PTSD, or a risk factor in the development of PTSD.
Researchers supporting the causal hypothesis have proposed that increased levels of cortisol
during the traumatic experience could be neurotoxic to the hippocampus. Several studies have
confirmed an increase in levels of cortisol during stress. However, plasma and urine
measures of cortisol in patients with PTSD are mixed; with reports of increased decreased or
normal cortisol. The possibility that increased sensitivity of the Type II or glucocorticoid
receptors to circulating cortisol could lead to neurotoxic damage to the hippocampus,
despite normal to low peripheral levels of cortisol has been proposed. Furthermore,
increased sensitivity of the glucocorticoid receptor in PTSD could lead to stronger negative
feedback inhibition, thereby offering a mechanism for the paradoxical observation of lower
ACTH and cortisol levels in PTSD. Studies attempting to test the glucocorticoid receptor
super sensitivity theory in PTSD confirmed the presence of increased number and sensitivity
of lymphocyte glucocorticoid receptors in patients compared to healthy subjects. However,
there are currently no published reports investigating central glucocorticoid sensitivity in
patients with PTSD. A recent study in healthy subjects and Alzheimer's disease demonstrated
that central glucocorticoid receptor sensitivity can be measured by hydrocortisone mediated
inhibition of glucose metabolism measured by positron emission tomography (PET) and
2-deoxy-2[F]fluoro-D-glucose (FDG). We propose to evaluate the metabolic, cognitive, and
behavioral effects of hydrocortisone or placebo administration in patients with PTSD,
subjects who have experienced trauma but do not develop PTSD (trauma controls) and healthy
1. The study sample will consist of:
Patients with a primary diagnosis of PTSD due to non-combat or combat related trauma
according to DSM-IV.
Subjects with non-combat related traumatic experiences without current PTSD and
Healthy subjects without current or past history of psychiatric or major medical
2. All subjects will be between 18 and 60 years old.
3. Male and female subjects will be included.
4. All subjects must be able to give written informed consent prior to participation in
5. Patients with PTSD must score greater than or equal to 50 on Clinician-Administered
PTSD Scale as a measure of PTSD symptom severity to be included in the study.
6. Patients who are not currently on medications for PTSD. (Patients will not be
discontinued from effective medication for purposes of the study).
7. Patients who are nonresponders to other psychotropic drugs must have discontinued
them for at least 2 weeks prior to the first PET scan. Medications will be
discontinued under the supervision of the treating physician or a research
psychiatrist listed in the protocol. (Nonresponders will be defined as subjects who
continue to meet criteria for PTSD despite treatment with 30 mg equivalent of
paroxetine for a minimum duration of six weeks).
7. All eligible subjects must be in good physical health as confirmed by a complete
physical exam (including normal vital signs), electrocardiogram, neurological exam, and
routine laboratory tests of blood and urine. [However, if patients have participated in
other research studies or have had blood work through their primary MD within the last 6
months, these results will be used instead of repeating blood draws for inclusion into the
1. Subjects with a clinically significant cardiovascular, pulmonary, endocrine,
neurological, gastrointestinal illness or unstable medical disorder.
2. Patients who would be unable to comply with study procedures or assessments.
3. Subjects with primary trauma related to motor vehicle accidents.
4. Patients who meet DSM-IV criteria for alcohol and/or substance abuse or substance
dependence within 6 months prior to screening.
5. Patients who are currently on fluoxetine (Justification: Washout from fluoxetine
could take up to six weeks).
6. Patients who are currently at high risk for homicide or suicide.
7. Subjects with a current or past history of other axis I disorders like schizophrenia,
schizoaffective disorder, bipolar disorder or dementia will be excluded from the
study. However, those with a comorbid history of other Axis 1 disorder like major
depression, dysthymia or panic disorder will be included in the study. Justification:
Approximately 70% of subjects with PTSD have comorbid depression and or alcohol
abuse; reviewed in 134. Restricting the sample to PTSD patients without depression
will not accurately reflect the biology of this disorder].
8. Subjects with a history of peptic ulcer disease will be excluded. (Justification:
Those with a history of acid peptic disease requiring antacids in the past will be
excluded, although it is unlikely that a single dose of intravenous hydrocortisone
could precipitate bleeding due to gastritis or peptic ulcer disease).
9. Women of childbearing potential who are not practicing a clinically accepted method
of contraception or who have a positive pregnancy test or who are lactating.
10. Subjects who donated a Red Cross unit of blood within 60 days prior to participation
in the study.