Typhoid Vaccine on Sleep Clinical Trial
Official title:
Investigating the Effects of Typhoid Vaccine on Sleep in Healthy Volunteers
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.
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.
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