Investigating the Effects of Typhoid Vaccine on Sleep in Healthy Volunteers
Condition: Typhoid Vaccine on Sleep
MeSH terms: Typhoid Fever
Study type: Interventional

Summary: 
      Research studies have found a relationship between the immune system (how the body reacts to
      an infection) and the development of depression. As it is still unclear how they might be
      linked the investigators will use a typhoid vaccination to activate the body's immune system
      and will measure the response by looking at changes in sleep patterns.
    

Detailed description: 
      Elevated levels of pro-inflammatory cytokines are implicated in the pathogenesis of major
      depression. Both clinical and animal studies have shown that pro-inflammatory cytokines can
      induce a behavioural repertoire of symptoms collectively referred to as 'sickness
      behaviours,' which include cognitive and mood symptoms, such as depression, anxiety, memory
      impairment, fatigue, anhedonia and sleep disturbance.

      Raised circulating pro-inflammatory cytokines exhibited during chronic medical illness, such
      as rheumatoid arthritis, are frequently associated with higher rates of co-morbid depression
      compared to the general population. Medically healthy individuals with major depression have
      also been shown to have raised pro-inflammatory cytokine levels. Moreover, administration of
      interferon-α (IFN-α), a recombinant form of inflammatory cytokine that is commonly used as a
      therapy for hepatitis C virus (HCV) and certain cancers, is well documented to precipitate
      depression and cognitive impairment in 30-50% of patients. In a previous study in this
      Department the investigators showed, using magnetic resonance spectroscopy (MRS), that IFN- α
      increased markers of glutamate activity. This is of particular interest because of the
      postulated role of glutamate in mood regulation and cognition.

      Converging evidence of the link between inflammation and depression has therefore led to the
      hypothesis that chronic low-grade inflammation could lead to more persistent alterations in
      neuropsychological function that might be instrumental in the pathogenesis of major
      depression. However, the mechanisms for this potential modulation of mood and cognitive
      function remain unclear.

      In order to examine the relationship between inflammation and depression, experimental models
      of inflammation have been developed that involve exogenous administration of cytokines or
      cytokine-inducers, for example salmonella typhi (typhoid) vaccination. This study will
      utilise typhoid vaccination as a model of acute inflammatory challenge in healthy volunteers,
      which has previously been shown to stimulate a mild, non-sickness inducing inflammatory
      response that significantly increases levels of the pro-inflammatory cytokine, interleukin
      (IL)-6, in a safe manner without increasing symptoms of illness, body temperature and blood
      pressure. This model has been shown to elicit a transient depression-like syndrome in healthy
      volunteers, including a range of behavioural changes such as cognitive dysfunction, fatigue
      and modulation of subjective ratings of mood. The investigators believe this will serve as a
      good model to investigate effects of immune activation on sleep.

      Sleep electroencephalogram (EEG) recordings will explore the effects of immune activation on
      sleep, as sleep changes are observed in clinical depression. Healthy volunteers will be
      recruited for this study, so that the investigators can investigate the effects of
      inflammatory challenge in participants that do not currently have an inflammatory condition.

      The present exploratory study therefore aims to enhance the investigators understanding of
      the intriguing link between inflammation and emotional dysfunction by examining the effects
      of inflammatory challenge using typhoid vaccine on sleep using a detailed psychiatric
      assessment and sleep EEG recordings.
    

Intervention name(s): Typhoid Vaccine; Placebo
Intervention type(s): Biological; Biological
Intervention description(s): Typhoid Vaccine injection given 7 days apart; Saline injection given 7 days apart
Other intervention name(s): Typhim Vi®; 0.9% sodium chloride saline solution
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: PSG; Typhoid Vaccine; Depression; Inflammation