Impact of Immune Challenge on Triple Network Connectivity in Humans

Study Overview
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Brief Summary
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Acquiring, processing and utilising information is crucial to any mental function -including seemingly simple daily functions. Collectively called 'cognitive functions', these processes are a result of different regions of the brain acting together. Disruption of these cognitive functions increases the risk of development of mental health problem. Recently it has been proposed that inflammatory pathways may contribute to disorders of cognition and behaviour like depression. This is largely due to research showing that those with inflammatory conditions like arthritis are more likely to develop mental health problems like depression. Conversely, those who suffer from mental health problems (even in the absence of inflammatory conditions) have large amounts of inflammatory molecules in the blood. Studies in animals suggest that inflammation outside the brain can reach and affect the brain in a number of ways. So, does inflammation play a role in the development of cognitive and behavioural symptoms? What are the pathways involved? The current project tries to address this question. Specifically, the investigators intend to use modern scanning techniques to examine the effect of inducing a low grade inflammation (using a commonly used typhoid vaccine) to see how the inflammation affects how different regions of the act together to perform cognitive functions.

Official Title
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Exploring the Impact of Peripheral Immune Challenge on the Triple Network and Dorsal Nexus Functional Connectivity in Humans

Conditions
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Major Depression

Intervention / Treatment
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* Biological: Salmonella typhi vaccination
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent Aged 18 - 50 years old Male Exclusion Criteria: Female History/family history of medical or/and Axis I DSM IV condition Received typhoid vaccination within the last 3 years Taken oral antibiotics/antiinflammatory agents within the previous 2 weeks Current Smokers Contraindication for MRI scans Contraindication for Salmonella typhi vaccination Known hypersensitivity to a Vi antigen containing vaccine.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Typhoid vaccination<br>Salmonella typhi vaccination | Biological: Salmonella typhi vaccination<br> <br> |
| Placebo Comparator: Placebo<br>0.9% sodium chloride | Biological: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional connectivity measured using resting state functional MRI BOLD time series cross correlations between the network nodes. |  | 6 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation of functional connectivity measures with circulating serum cytokines and POMS/ BDI scores using multivariate general linear models |  | 6 hours |