Imaging the Neuroimmune System in PTSD
Study Details
Study Description
Brief Summary
In this study, individuals with and without post-traumatic stress disorder (PTSD) will undergo one positron emission tomography (PET) scan using the radiotracer [11C]PBR28, which binds to the 18kDa translocator protein (TSPO). A subset of individuals who complete the first PET [11C]PBR28 scan will be invited to complete an inflammatory challenge and second PET [11C]PBR28 scan. Approximately 3 hours prior to the second [11C]PBR28 PET scan, lipopolysaccharide (LPS; endotoxin) will be administered to evoke a robust neuroimmune response. Subjects will also undergo behavioral and cognitive testing. Vital signs, subjective response, and peripheral biomarker levels will be assayed periodically throughout the experimental session.
Specific aims: 1) Determine if individuals with PTSD exhibit neuroimmune system disruption relative to well-matched comparators at baseline. 2) Determine if individuals with PTSD exhibit a disrupted neuroimmune response after a classical immune stimulus relative to well-matched comparators. 3) Determine if LPS differentially alters cognitive function, subjective response, or physiological markers in individuals with PTSD compared to well-matched comparators.
Hypothesis: Individuals with PTSD will exhibit a suppressed neuroimmune system at baseline and an attenuated neuroimmune response following LPS challenge, relative to matched trauma controls.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| No Intervention: Baseline [11C]PBR28 PET Scan Subjects will complete a 120-minute baseline [11C]PBR28 PET scan. |
|
| Experimental: Post-LPS [11C]PBR28 PET Scan Subjects will complete a second120-minute [11C]PBR28 PET scan 3-hours after LPS administration (1.0ng/kg; IV) |
Drug: Lipopolysaccharide
LPS will be administered intravenously (1.0ng/kg; IV)
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Baseline TSPO Availability [Before LPS administration (baseline)]
Time-activity curves will be extracted from brain regions of interest and analyzed using multilinear analysis-1 (t*=30) incorporating the metabolite-corrected arterial input function to yield [11C]PBR28 total volumes of distribution (VT) across brain regions.
- Post-LPS TSPO Availability [3-hours after LPS administration (1.0 ng/kg; IV)]
Time-activity curves will be extracted from brain regions of interest and analyzed using multilinear analysis-1 (t*=30) incorporating the metabolite-corrected arterial input function to yield [11C]PBR28 total volumes of distribution (VT) across brain regions.
Secondary Outcome Measures
- Baseline Visual Attention [Before LPS administration]
Visual attention: response latency to identify card color (log10(ms); higher ~ worse attention).
- Post-LPS Visual Attention [Approximately ~1-hour after LPS administration]
Visual attention: response latency to identify card color (log10(ms); higher ~ worse attention).
- Baseline Visual Learning [Before LPS administration]
Visual learning: % of correctly identified repeat cards (arcsine(% correct); higher values ~ better learning).
- Post-LPS Visual Learning [Approximately ~1-hour after LPS administration]
Visual learning: % of correctly identified repeat cards (arcsine(% correct); higher values ~ better learning).
- Baseline Verbal Memory [Before LPS administration]
Verbal memory: # of correctly recalled items from a grocery list (3 trials). Verbal recall: # of correctly recalled items from a grocery list after a delay (1 trial; higher ~ better memory/recall).
- Post-LPS Verbal Memory [Approximately ~1-hour after LPS administration]
Verbal memory: # of correctly recalled items from a grocery list (3 trials). Verbal recall: # of correctly recalled items from a grocery list after a delay (1 trial; higher ~ better memory/recall).
- Baseline Executive Function [Before LPS administration]
Executive function: number of errors navigating a 'hidden' maze (5 trials; higher ~ worse executive function).
- Post-LPS Executive Function [Approximately ~1-hour after LPS administration]
Executive function: number of errors navigating a 'hidden' maze (5 trials; higher ~ worse executive function).
- Baseline Visual-Motor Processing Speed [Before LPS administration]
Visual-motor processing speed: response latency to detect a card flipped over (log10(ms); higher ~ worse processing speed).
- Post-LPS Visual-Motor Processing Speed [Approximately ~1-hour after LPS administration]
Visual-motor processing speed: response latency to detect a card flipped over (log10(ms); higher ~ worse processing speed).
- Baseline Working Memory [Before LPS administration]
Working memory: % of correctly identified cards that matched the card presented either one- or two-cards previously (arcsine(% correct); higher ~ better working memory).
- Post-LPS Working Memory [Approximately ~1-hour after LPS administration]
Working memory: % of correctly identified cards that matched the card presented either one- or two-cards previously (arcsine(% correct); higher ~ better working memory).
- Baseline Social Cognition [Before LPS administration]
Social cognition: response latency to identify the mismatched facial expression based on its emotional content (ms; log10; higher ~ worse social cognition).
- Post-LPS Social Cognition [Approximately ~1-hour after LPS administration]
Social cognition: response latency to identify the mismatched facial expression based on its emotional content (ms; log10; higher ~ worse social cognition).
- Baseline Reward Responsiveness [Before LPS administration]
Reward responsiveness will be quantified via computerized Probabilistic Reward Task
- Post-LPS Reward Responsiveness [Approximately ~2-hour after LPS administration]
Reward responsiveness will be quantified via computerized Probabilistic Reward Task
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Men and women, aged 18-55 years
-
Subjects with PTSD will have a primary, current diagnosis of PTSD according to DSM-V criteria (i.e., CAPS-5 ascertained diagnosis)
-
Able to read and write English and to provide voluntary, written informed consent
Exclusion Criteria:
-
Current medical condition such as neurological, cardiovascular, endocrine, renal, liver, or thyroid pathology including COPD, anemia, uncontrolled daily asthma or asthma requiring the use of an inhaler more than 1x/week with an ACT score below 20. [We will not exclude individuals taking SSRIs and TRIs due to high prevalence of use within the PTSD population and due to evidence suggesting no effect of these drug classes on endotoxin response].
-
Past or current neurological disorder or disorders affecting the brain including but not limited to multiple sclerosis, history of stroke, brain tumors, traumatic brain injury with loss of consciousness, seizure disorder
-
Current or regular use of over-the-counter medication that may affect the immune system
-
Women who are pregnant or nursing, or fail to use one of the following methods of birth control unless she or partner is surgically sterile or she is postmenopausal (hormone contraceptives [oral, implant, injection, patch, or ring], contraceptive sponge, double barrier [diaphragm or condom plus spermicide], or IUD
-
Contraindications to MRI such as claustrophobia or metal in their body
-
Individuals who are classified as "low binders" for the rs6971 polymorphism (<10% of the population)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Yale University | New Haven | Connecticut | United States | 06519 |
Sponsors and Collaborators
- Yale University
Investigators
- Principal Investigator: Kelly Cosgrove, PhD, Yale University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2000020347