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.
Name: Lipopolysaccharide
Description: 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.
Measure: Baseline TSPO Availability Time: Before LPS administration (baseline)Description: 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.
Measure: Post-LPS TSPO Availability Time: 3-hours after LPS administration (1.0 ng/kg; IV)Description: Visual attention: response latency to identify card color (log10(ms); higher ~ worse attention). Visual learning: % of correctly identified repeat cards (arcsine(% correct); higher values ~ better learning). 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). Executive function: number of errors navigating a 'hidden' maze (5 trials; higher ~ worse executive function). Visual-motor processing speed: response latency to detect a card flipped over (log10(ms); higher ~ worse processing speed). Working memory: % of correctly identified cards that matched the card presented either one- or two-cards previously (arcsine(% correct); higher ~ better working memory). Social cognition: response latency to identify the mismatched facial expression based on its emotional content (ms; log10; higher ~ worse social cognition).
Measure: Baseline Cogstate Cognitive Battery performance Time: Before LPS administrationDescription: Visual attention: response latency to identify card color (log10(ms); higher ~ worse attention). Visual learning: % of correctly identified repeat cards (arcsine(% correct); higher values ~ better learning). 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). Executive function: number of errors navigating a 'hidden' maze (5 trials; higher ~ worse executive function). Visual-motor processing speed: response latency to detect a card flipped over (log10(ms); higher ~ worse processing speed). Working memory: % of correctly identified cards that matched the card presented either one- or two-cards previously (arcsine(% correct); higher ~ better working memory). Social cognition: response latency to identify the mismatched facial expression based on its emotional content (ms; log10; higher ~ worse social cognition).
Measure: Post-LPS Cogstate Cognitive Battery performance Time: Approximately 1-hour after LPS administrationAllocation: Non-Randomized
Parallel Assignment
There is one SNP
Individuals who are classified as "low binders" for the rs6971 polymorphism (<10% of the population) Inclusion Criteria: 1. Men and women, aged 18-55 years 2. Subjects with PTSD will have a primary, current diagnosis of PTSD according to DSM-V criteria (i.e., CAPS-5 ascertained diagnosis) 3. Able to read and write English and to provide voluntary, written informed consent Exclusion Criteria: 1.
Individuals who are classified as "low binders" for the rs6971 polymorphism (<10% of the population) Post Traumatic Stress Disorder Stress Disorders, Traumatic Stress Disorders, Post-Traumatic null