Elevated levels of pro-inflammatory cytokines are implicated in the pathogenesis of major depression. Human 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, social withdrawal and sleep disturbance. When likened to clinical depression, these symptoms appear to be strikingly similar. Moreover, subsets of depressed patients have raised inflammatory markers, 30-50% of patients receiving cytokine treatment in the form of interferon-α (IFN-α) therapy develop depressive symptoms, and significantly higher rates of depression are associated with chronic inflammatory conditions, such as rheumatoid arthritis (RA). Converging evidence has led to the hypothesis that chronic, low-grade inflammation could lead to more persistent alterations in neuropsychological function that might be instrumental in the pathophysiology of depression. However, the mechanisms for this potential modulation of mood and cognitive function are unclear. The current thesis therefore aimed to enhance understanding of the neuropsychological underpinnings of the link between inflammation and depression. Negative emotional processing biases are well-recognised in the aetiology of depression; however potential inflammation-induced alterations in emotional processing remain unexplored. Thus, a series of studies were conducted using human models of immune system activation to examine neuropsychological function. The first study demonstrated that IFN-α treatment in patients with hepatitis C produced negative biases in emotional categorisation, attentional vigilance and a specific effect of enhanced recognition of disgust. The subsequent study found a specific effect of false discrimination of disgusted faces in a healthy volunteer model of inflammatory challenge with typhoid vaccination, however further effects on emotional processing were limited. Typhoid vaccination was also shown to disrupt sleep continuity in ways that may be relevant to depression in the third study. Negative biases were not evident, however, in patients with RA. The final study found that neuropsychological effects of the atypical antidepressant tianeptine were similar to effects following IFN-α, which may be of interest considering tianeptine's purported serotonergic re-uptake enhancing properties and the effects of cytokines on serotonin metabolism. This thesis provides intriguing, yet preliminary, evidence that inflammatory pathways may modulate emotional processing - a mechanism which, if supported, may have future implications for improved identification and treatment of subgroups of depressed patients.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:730343 |
| Date | January 2016 |
| Creators | Cooper, Charlotte |
| Contributors | Harmer, Catherine |
| Publisher | University of Oxford |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | https://ora.ox.ac.uk/objects/uuid:f5e956e4-fa87-450b-b382-571f589e39b3 |
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