Lawes, Samantha; (2020) Depression and inflammation: implications for cardiovascular disease. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

There is extensive evidence linking inflammation with depression, but the nature of this relationship remains unclear. This PhD consisted of two studies that aimed to investigate the interaction of immune and neuroendocrine function in major depressive disorder (MDD) and examine the effects of depressive symptoms and inflammation on mortality risk. Study 1 sought to garner more information about the relationship between immune activation and HPA-axis function using data from an observational, case-control study including people with MDD and healthy controls. In Study 1a differences in inflammatory cytokines and HPA-axis function, and associations between them were examined. Results indicated increased inflammation, a flattened cortisol awakening response under the curve (CAR AUC) and impaired corticosteroid function in depressed people. Furthermore there was evidence of a negative association between inflammation and diurnal cortisol rhythm. In Study 1b changes in depressive symptoms, inflammatory cytokines and HPA-axis function were investigated longitudinally in people with MDD. The results demonstrated an improvement in depressive symptoms and mineralocorticoid sensitivity. We also observed a trend towards an improvement in the CAR AUC and an apparent trend towards a negative pattern of association between change in inflammation and change in the CAR. In Study 1c differences in Treg frequency were assessed between people with MDD and healthy controls. The findings showed no difference between the groups and no association with either inflammation or HPA-axis function. Study 2 investigated the combined effects of depressive symptoms and inflammation on CVD and all-cause mortality risk in a longitudinal cohort study of older people. The results showed that the combination of both factors confers a considerable increase in CVD mortality risk for men. Together these studies indicate that there is a relationship between inflammation and HPA-axis dysfunction in MDD and that men with depressive symptoms and increased inflammation constitute a high-mortality risk phenotype.

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