Neuroimmune Response to Lipopolysaccharide

Yale University27 enrolled

Overview

In this study, healthy adult volunteers will undergo two positron emission tomography (PET) scans using the radiotracer \[11C\]PBR28 which binds to the 18kDa translocator protein (TSPO). 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 cytokine levels will be assayed periodically throughout the experimental session. Specific aims: Quantify the magnitude of neuroimmune response after a classical immune stimulus. Secondary aims: Quantify changes in cognitive function after a classical immune stimulus. Hypothesis: Individuals will exhibit a robust whole-brain neuroimmune response and impaired cognitive function after LPS.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Healthy

Interventions

Eligibility

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

Medical Language ↔ Plain English

Inclusion Criteria: 1\) Medically-healthy male and female subjects able to read/write English Exclusion Criteria: 1. Subjects cannot meet DSM criteria for substance use disorder 2. Any psychiatric symptoms that could put the subject at risk by participating in the study including but not limited to suicidal or homicidal ideation, or suicide attempt within the last year 3. Pregnancy or breastfeeding; 4. Any current medical illness that could put the subjects at risk during the PET scan, or interfere with the PET or immunologic measures 5. Significant hepatocellular injury (as evidenced by AST or ALT levels greater than 5 times normal or a history of cirrhosis) will be exclusionary in order to reduce the risks associated with alcohol consumption 6. Subjects taking corticosteroids or other immunosuppressant drugs 7. Subjects with disorders affecting the brain, including but not limited to multiple sclerosis, history of stroke, brain tumors, intracranial bleeding, infection, or abscess.

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)

Secondary Outcomes

Alcohol Dependence Scale (ADS) - questionnaire

self-report questionnaire to determine severity of alcohol symptoms, 25 question multiple choice scale, range of 0-47 for a total score, with higher numbers indicating worse severity

Time frame: baseline