Cortisol Supression and Startle Responses in Posttraumatic Stress Disorder (PTSD)
| Status: | Completed |
|---|---|
| Conditions: | Psychiatric |
| Therapuetic Areas: | Psychiatry / Psychology |
| Healthy: | No |
| Age Range: | 18 - 65 |
| Updated: | 4/21/2016 |
| Start Date: | November 2011 |
| End Date: | July 2015 |
Effects of Cortisol Suppression on Fear-Potentiated Startle in Traumatized Individuals With and Without PTSD
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.
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.
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.
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.
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)
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