Inflammation and Threat Sensitivity in PTSD
Condition: Posttraumatic Stress Disorder
MeSH terms: Inflammation; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
Study type: Interventional
Phase: Early Phase 1

Summary: 
      The overall goals of this study are to examine the relationship between chronic inflammation
      and threat and reward sensitivity, and to determine the effects of acute inflammation on
      threat sensitivity, in individuals with and without moderate to severe PTSD symptoms. The
      investigators will first conduct an observational study to examine the relationship between
      chronic inflammation and neural and behavioral measures of threat sensitivity. Then, the
      investigators will conduct a randomized, double-blind, placebo-controlled, between-subjects
      study to examine the effects of acute inflammation on neural and behavioral measures of
      threat sensitivity.
    

Detailed description: 
      Posttraumatic stress disorder (PTSD) is a disabling chronic psychiatric disorder that affects
      more than 8% of the population. New treatments for PTSD symptoms are desperately needed
      because current pharmacologic and behavioral treatments for PTSD are inadequate or they have
      low uptake. Accumulating evidence supports elevated inflammation as a new potential treatment
      target for PTSD. Inflammation is increased in PTSD, and can promote threat sensitivity, a
      core mechanism underlying several PTSD symptoms. Two major gaps in knowledge prevent progress
      towards effective anti- inflammatory treatments for PTSD symptoms. First, researchers know
      little about the relationship between chronic inflammation and exaggerated threat
      sensitivity. Second, no studies have directly examined the effects of acute inflammation on
      neural and behavioral measures of threat sensitivity in PTSD. The objective of this study is
      to uncover the effects of chronic and acute inflammation on neural mechanisms and behavioral
      measures of threat sensitivity in individuals with and without PTSD symptoms. The central
      hypothesis is that both chronic and acute inflammation will be associated with exaggerated
      threat sensitivity overall, with particularly strong relationships in PTSD. The scientific
      rationale is that establishing a link between elevated inflammation and threat sensitivity in
      both observational and experimental studies in individuals with and without PTSD symptoms
      will drive progress towards a targeted approach to identifying effective anti- inflammatory
      treatments for PTSD symptoms. In particular, this work has the potential to identify a target
      for clinical trials of anti-inflammatory interventions in PTSD. Guided by preliminary data,
      hypotheses will be tested by pursuing two specific aims: 1) Examine the association of
      chronic inflammation with threat sensitivity; and 2) Determine the effects of an acute
      inflammatory challenge on threat sensitivity. To achieve these aims, 40 participants with
      moderate to severe PTSD symptoms and 40 age- and body mass index-matched trauma-exposed
      participants with no history of PTSD will be recruited. The investigators will assess chronic
      resting levels of inflammation (Aim 1) and will randomize participants to placebo or
      inflammatory challenge using polysaccharide typhoid vaccine (i.e., endotoxin) (Aim 2) and
      will use validated functional MRI paradigms and behavioral tasks to assess threat
      sensitivity.
    

Intervention name(s): Typhoid Vi Polysaccharide Vaccine; Placebo
Intervention type(s): Biological; Biological
Intervention description(s): Salmonella typhi capsular polysaccharide vaccine (Typhoid Vi Polysaccharide Vaccine): Each dose of 0.5ml Salmonella typhi capsular polysaccharide vaccine (Sanofi Pasteur, SA) is formulated to contain 25μg of purified Vi polysaccharide in a colorless isotonic phosphate buffered saline (pH 7±0.3), 4.150mg of sodium chloride, 0.065mg of disodium phosphate, 0.023mg of monosodium phosphate and 0.5ml of sterile water for injection. It is indicated for use by humans aged 2 years and older for protection against typhoid fever.; The placebo injection will consist of 0.5mL of saline.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science