Imaging the Neuroimmune System in PTSD

Yale University34 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Post Traumatic Stress Disorder

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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. 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. \[We will not exclude individuals taking SSRIs and TRIs due to high prevalence of use within the PTSD population and due to evidence suggesting no effect of these drug classes on endotoxin response\]. 2. 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 3. Current or regular use of over-the-counter medication that may affect the immune system 4. 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 5. Contraindications to MRI such as claustrophobia or metal in their body 6. Individuals who are classified as "low binders" for the rs6971 polymorphism (\<10% of the population)

Outcomes

Primary Outcomes

Baseline TSPO Availability

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.

Time frame: Before LPS administration (baseline)

Post-LPS TSPO Availability

Time frame: 3-hours after LPS administration (1.0 ng/kg; IV)

Secondary Outcomes

Baseline Visual Attention

Visual attention: response latency to identify card color (log10(ms); higher \~ worse attention).

Time frame: Before LPS administration

Post-LPS Visual Attention

Visual attention: response latency to identify card color (log10(ms); higher \~ worse attention).