Mapping the Effect of (neuro)inflammation on Stress Sensitivity in the Brain of Healthy Men

The goal of this interventional study is to determine the effects of inflammation on stress responses in the brain of healthy men. In order to achieve this goal, participants are injected with an inflammation-inducing agent, then observed inside a brain scanner.

This interventional study is a randomized, triple-blind, placebo-controlled, cross-over study aiming to elucidate the impact of acute laboratory-induced inflammation using lipopolysaccharide (LPS) on stress responses in the brain of healthy men. Acute stress responses to a psychological task, the Maastricht Imaging Stress Task (MIST), are observed via blood-oxygenation-level-dependent functional magnetic resonance imaging (BOLD fMRI) and simultaneous positron emission tomography (PET) imaging using the radiotracer 18 Fluor (18F)-N,N-diethyl-2-\[4-(2-fluoroethoxy)phenyl\]-5,7-dimethylpyrazole\[1,5-a\]pyrimidine-3-acetamide (DPA)-714, which targets the 18 kilodalton (kDA) translocator protein (TSPO) of activated microglia. Every participant will receive 0.4 ng/kg body weight of LPS and saline on separate treatment visits, separated by a 2-3 months wash-out period.

Eligibility Criteria:
Inclusion Criteria:

* Male
* Healthy
* Age 18-45 years
* BMI 18.5-25 kg/m2
* Proficient in English and/or Dutch

Exclusion Criteria:

* Have previous or current neuropsychiatric disorders or have history of major head trauma
* Have any disorder, which in the Investigator's opinion might jeopardise your safety or compliance with the study
* Have any prior or current treatment(s) that might jeopardise your safety or that would compromise the integrity of the study
* Have any prior and recent medication use (especially antibiotics, cardiovascular drugs, steroids, non-steroid anti-inflammatory drugs, centrally effective drugs)
* Are participating in an interventional Trial with an investigational medicinal product (IMP) or device
* Have current or previous infection or vaccination within the last 8 weeks
* Have pathological values of blood indices and certain genetic profiles that will affect brain imaging results (we will conduct a blood screening before starting the study)
* Had strong physical activity (e.g. swimming, football, running more than 8 km per hour, carrying heavy loads) 24h before the start of the experiment.
* Are a smoker
* Are a night-shift worker
* Have recent or previous use of psychotropics within the last year
* Have regular high alcohol use (\>4 drinks/week)
* Have any brain imaging contraindications:

  * Have claustrophobia or too much uneasiness in limited spaces (in order to tolerate confinement during the scanning procedures).
  * Have severe back problems that will interfere with lying on your back in the scanner with no movement for long durations.
  * Have any condition that would interfere with MRI studies (e.g., cochlear implant, metal fragments in eyes, cardiac pacemaker, neural stimulator, and metallic body inclusion or other metal implanted in the body). To check this, you will need to fill out a checklist before the procedure.
* You and/or your partner is planning to become pregnant during and up to one month of the completion of the study