CB1 Receptor PET Imaging Reveals Gender Differences in PTSD

Study Overview
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Brief Summary
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The objective of the proposed translational study is to test a model, based upon basic science studies, exploring multisystem impairments in PTSD including endocannabinoid (eCB) and glucocorticoids in the modulation of fear memories by examining the cannabinoid type 1 (CB1) receptor in a PTSD fear circuit as well as glucocorticoid function. The investigators propose that impaired eCB signaling in PTSD resulting in the maladaptive neurobehavioral response to the stressor is associated with an upregulation of the CB1 receptors and insufficient glucocorticoid signaling.

Detailed Description
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The eCB - anandamide and 2-arachidonoylglycerol (2-AG) - and their attending cannabinoid (CB) receptors which are found in high densities in a fear circuitry involving the amygdala, hippocampus, the anterior cingulate cortex and prefrontal cortex serve important functions in the regulation of stress-coping behaviors. Besides eCB regulation there is strong evidence from ongoing research of the investigators group and others suggesting an important role for glucocorticoid signaling as an endpoint of the biochemical sequelae initiated by stressful or aversive stimuli. One of the long-term research goals of our lab is to understand such functions and determine their relevance to the pathogenesis of PTSD and to provide a more integrative view on neurobiological mechanisms that are involved in the regulation of the neuroadaptive response to stress. The objective of the proposed translational study is to test a model, based upon basic science studies, exploring multisystem impairments in PTSD including eCB and glucocorticoids in the modulation of fear memories by examining the CB1 receptor in a PTSD fear circuit as well as glucocorticoid function. The investigators propose that impaired eCB signaling in PTSD resulting in the maladaptive neurobehavioral response to the stressor is associated with an upregulation of the CB1 receptors and insufficient glucocorticoid signaling.

Official Title
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Cannabinoid-1 (CB1) Receptor Positron Emission Tomography (PET) Imaging Reveals Gender Differences in Posttraumatic Stress Disorder (PTSD)

Conditions
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Post-traumatic Stress Disorder (PTSD)

Intervention / Treatment
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* Other: Positron emission tomography (PET) imaging


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for Patients with PTSD: age 18-55 years old currently diagnosed with PTSD and symptomatic with a Clinician-Administered PTSD Scale (CAPS) score > 50. Inclusion Criteria for healthy subjects: age 18-55 years old no personal or first-degree family history of any Axis I diagnosis. Exclusion criteria for Patients with PTSD: any primary Axis I disorder other than PTSD (e.g. psychosis); medical or neurological illnesses likely to affect physiology or anatomy, i.e. uncontrolled hypertension, cardiovascular disorders; a history of drug (including benzodiazepines (BZD)) dependence (DSM IV criteria) within 1 year of the study and lasting longer than 2 years, except for alcohol dependence current pregnancy (as documented by pregnancy testing at screening or on the day of PET imaging study) current breast feeding nicotine dependence suicidal ideation or behavior general MRI exclusion criteria, i.e. pacemakers, metals in the body Human immunodeficiency virus (HIV) (due to possible neuropsychiatric effects); use of opioid medications within 2 weeks of the PET study having an abnormality in the 12-lead ECG that, in the opinion of the investigator, increases the risks associated with participation in the study seriously claustrophobic blood donation within 8 weeks prior to the study. Exclusion criteria for healthy subjects: any history or current primary Axis I disorder medical or neurological illnesses likely to affect physiology or anatomy, i.e. uncontrolled hypertension, cardiovascular disorders a history of drug (including benzodiazepines [BZD]) dependence (DSM IV criteria) within 1 year of the study and lasting longer than 2 years, except for alcohol dependence current pregnancy (as documented by pregnancy testing at screening or on the day of PET imaging study) current breast feeding nicotine dependence suicidal ideation or behavior general MRI exclusion criteria, i.e. pacemakers, metals in the body HIV (due to possible neuropsychiatric effects) use of opioid medications within 2 weeks of the PET study having an abnormality in the 12-lead ECG that, in the opinion of the investigator, increases the risks associated with participation in the study seriously claustrophobic blood donation within 8 weeks prior to the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Post-traumatic stress disorder (PTSD)<br>Post-traumatic stress disorder (PTSD) | Other: Positron emission tomography (PET) imaging<br>* Positron emission tomography (PET) imaging<br>|
| Healthy Controls (HC)<br>Healthy Controls (HC) | Other: Positron emission tomography (PET) imaging<br>* Positron emission tomography (PET) imaging<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Volume of distribution (VT) of cerebral CB1 receptor expression in PTSD and controls within a fear circuit of brain regions that regulate stress-related behaviors using the CB1 radioligand carbon - 11 (11C) [11C]OMAR and PET. | To examine group differences in cerebral CB1 receptor expression in PTSD and controls within a fear circuit of cortical and subcortical brain regions that regulate stress-related behaviors using the CB1 radioligand [11C]OMAR and PET. Hypothesis: PTSD patients will show greater [11C]OMAR VT (i.e. CB1 binding) values than both control groups, trauma-exposed and non-trauma exposed control subjects who will not be different. | Two months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Trauma, Neuroimaging, Positron emission tomography (PET), [11C]OMAR, Endocannabinoid, Post-traumatic stress disorder (PTSD)