Cortisol Supression and Startle Responses in Posttraumatic Stress Disorder (PTSD) — CSS  

PTSD Clinical Trial

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

Status Completed

Clinical Trial Summary

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, we 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. We 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.

Clinical Trial Description

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. Our recent discovery that cortisol suppression reduces fear responses in PTSD coupled with the development of new fear conditioning paradigms, provides a unique opportunity to interrogate amygdala-HPA interactions to determine aspects of the neurobiological underpinnings of PTSD-related pathology.

AIM 1: Does HPA suppression decrease fear-potentiated startle in subjects with PTSD? Evidence from our preliminary studies suggests that subjects with PTSD have exaggerated expression of fear responses to danger and safety cues after fear acquisition, and that cortisol suppression reduces this pathological fear.

• 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.

HYPOTHESIS: We predict, based on our preliminary data, that the heightened physiological fear responses in PTSD patients relative to controls will be normalized with cortisol suppression, while cognitive awareness will not be altered. These data will provide new and important tools to further understand the role of dynamic regulation of the HPA axis and its modulation of the human fear response.

AIM 2: Does HPA suppression enhance extinction of fear-potentiated startle in subjects with PTSD? Evidence from our preliminary studies suggests that subjects with PTSD have exaggerated fear responses to the danger cue during fear extinction, and that cortisol suppression facilitates extinction.

• 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.

HYPOTHESIS: We predict, based on our preliminary data, that the heightened physiological fear responses in PTSD patients relative to controls during extinction will be reduced thereby facilitating extinction with cortisol suppression, while cognitive awareness will not be altered. These data will both extend our understanding of HPA regulation of extinction of fear, as well as provide a direct, testable new therapeutic approach to enhancing extinction (through exposure therapy) in a clinical PTSD population. ;

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• PTSD
• Stress Disorders, Post-Traumatic

• NCT number: NCT01477762
• Study type: Interventional
• Source: Emory University
• Status: Completed
• Phase: N/A
• Start date: November 2011
• Completion date: July 2015