Cortisol Suppression and Startle Responses in Posttraumatic Stress Disorder (PTSD)

Study Overview
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Brief Summary
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Posttraumatic stress disorder (PTSD) occurs in some people after exposure to events that cause extreme fear or helplessness. The incidence of war zones worldwide and the prevalence of violence in large cities in the U.S., increases the likelihood that people will experience a traumatizing event in their lifetime. About 1 in 10 people who survive such events will develop PTSD, while most people will get better over time. This suggests that some people may have biological vulnerabilities that make it harder for them to recover. One of these biological risk factors may be related to how stress hormones work in people who get sick. Another is how people react to things that make them afraid or nervous, investigators have found that PTSD patients have higher than normal fear reactions. The part of the brain that reacts to fearful stimulation is linked to stress hormones; the purpose of this study is to examine how these systems interact. The study will suppress stress hormones (cortisol) production in one group of participants, while another will get a placebo. When their cortisol is suppressed, the participants will undergo a startle study to see if their fear responses are decreased. Investigators expect that people PTSD will show a normal fear response when their cortisol levels are reduced, similar to people without PTSD. This research can help discover new medicines for people with PTSD.

Detailed Description
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The proposed study will provide innovative tools to tease apart the relationship between amygdala-dependent neurophysiology and HPA-axis sensitivity in a human clinical population. Investigators have discovered that cortisol suppression reduces fear responses in PTSD coupled with the development of new fear conditioning paradigms, providing a unique opportunity to interrogate amygdala-HPA interactions to determine aspects of the neurobiological underpinnings of PTSD-related pathology. Aim 1a will examine baseline and fear-potentiated startle (FPS) response, as well as cognitive awareness in PTSD patients and traumatized Non-PTSD controls during a fear conditioning experiment 10 hours after dexamethasone administration in a double-blind, placebo controlled crossover design. Aim 1b will examine the above outcome measures in PTSD patients and controls during a fear conditioning experiment 1 hour after dexamethasone administration in order to control for direct effects of dexamethasone. Aim 2a will examine fear-potentiated startle (FPS) response in PTSD patients and traumatized Non-PTSD controls during fear extinction, when the fear is acquired 10 hours after dexamethasone administration in a double-blind, placebo controlled crossover design. Aim 2b will examine the same outcome measures in PTSD patients and controls, when the fear is acquired 1 hour after dexamethasone administration in order to control for direct effects of dexamethasone.

Official Title
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Effects of Cortisol Suppression on Fear-Potentiated Startle in Traumatized Individuals With and Without PTSD

Conditions
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Post Traumatic Stress Disorder

Intervention / Treatment
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* Drug: Dexamethasone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to give informed consent Willing to participate in initial assessment and 2 full days of interviews and imaging visit Able to understand English and no obvious deficit in comprehension or following directions 18-65 years old Exclusion Criteria: Mental Retardation (per clinical judgment of study physician) Psychotic Disorder (per clinical judgment of study physician) Acute suicidal ideation Pregnancy Positive urine drug screen Active medical disorders contributing to psychiatric sx e.g. hypo or hyperthyroidism, SLE, advanced cirrhosis, etc. (per clinical judgment of study physician)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: PTSD Negative<br>Participants who do not have PTSD will receive placebo and dexamethasone in random order for the duration of two consecutive study visits separated by at least one month. | Drug: Dexamethasone<br>* One tablet of 0.5 mg dexamethasone will be taken ten hours prior to completing study assessments.<br>Drug: Placebo<br>* One placebo tablet will be taken ten hours prior to completing study assessments.<br>|
| Experimental: PTSD Positive<br>Participants with PTSD will receive placebo and dexamethasone in random order for the duration of two consecutive study visits separated by at least one month. | Drug: Dexamethasone<br>* One tablet of 0.5 mg dexamethasone will be taken ten hours prior to completing study assessments.<br>Drug: Placebo<br>* One placebo tablet will be taken ten hours prior to completing study assessments.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Baseline Startle Magnitude During Fear Conditioning | The study measured the acoustic startle response magnitude to a sudden noise using electromyography of the eyeblink muscle. This response magnitude was used as the individual's baseline to compare to the startle magnitude to the danger signal to see if fear conditioning had occurred. | 10 hours after drug administration | 
| Mean Startle Magnitude to Danger Signal During Fear Conditioning | The acoustic startle response magnitude was measured using electromyography recordings of the eyeblink muscle when a sudden tone was delivered through headphones in the presence of a stimulus that was paired with an aversive outcome (i.e. the danger signal). If an individual showed successful fear learning, then startle to the danger signal would be greater than baseline startle. | 10 hours after drug administration | 
| Mean Fear-potentiated Startle to Danger Signal During Early Extinction | Fear-potentiated startle was measured as a difference score between the startle to danger signal and the baseline. This difference score reflects the degree of fear response at the beginning of extinction. | 10 hours after drug administration | 
| Mean Fear-potentiated Startle to Danger Signal During Late Extinction | This measures the level of fear-potentiated startle (the difference between startle magnitude to the danger signal and baseline startle magnitude) at the end of extinction. Because the danger signal is no longer paired with the aversive stimulus like it was during the conditioning phase, the fear response should decrease from early to late extinction in individuals who show intact extinction learning. | 10 hours after drug administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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startle response, fear conditioning, PTSD