Risk of depression and cardiovascular disease across the lifespan: the role of systemic inflammation.
University of Cambridge
Doctor of Philosophy (PhD)
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Chaplin, A. (2021). Risk of depression and cardiovascular disease across the lifespan: the role of systemic inflammation. (Doctoral thesis). https://doi.org/10.17863/CAM.78701
Both depression and cardiovascular disease (CVD) affect millions of people worldwide and account for considerable mortality. In adults, comorbidity between these conditions is common, suggesting that shared pathophysiological mechanisms, such as systemic inflammation, may be involved. However, the direction of association between depression and CVD risk in young people remains unclear. Gaps also remain in our understanding of the role of different immune components in these relationships across the lifespan. The purpose of this thesis was two-fold. First, to investigate the association between CVD risk (as defined by systolic blood pressure, total cholesterol, low-density lipoprotein, high-density lipoprotein, high body mass index, and smoking status) and depressive symptoms in young people. Second, to test the convergence of evidence for systemic inflammation as a shared mechanism for depression and CVD across the lifespan. I conducted a systematic review and meta-analysis of longitudinal studies of CVD risk factors and subsequent depressive symptoms in young people. Then I used data from two contrasting observational studies: the Avon Longitudinal Study of Parents and Children (ALSPAC) and the United Kingdom (UK) Biobank to study associations between inflammation, depression, and CVD risk in different age groups. ALSPAC is a prospective birth cohort of 15,000 individuals born in and around Bristol in 1990/91. In contrast, UK Biobank is a long-term UK-based study of over 500,000 individuals aged 40 years old and over. I used several measures of systemic inflammation including interleukin-6 (IL-6), C-reactive protein (CRP), white blood cell count (WCC), and number of childhood infections. Through the systematic review and meta-analysis, I highlighted that obesity and cigarette smoking are strongly associated with depressive symptoms in individuals up to age 24 years. Few longitudinal studies of young people have considered the effect of other CVD risk factors such as systolic blood pressure, total cholesterol, low-density lipoprotein, or high-density lipoprotein. I followed PRISMA guidelines when reporting these findings. Using ALSPAC data, I revealed that CVD risk is associated with subsequent depressive symptoms but not the other way around. Obesity and cigarette smoking in particular appear to drive this association. These findings suggest that targeting smoking and obesity in young people may be important for the prevention of both depression and CVD in adults. I also used ALSPAC to study the effects of inflammatory markers on health outcomes in young people. Specifically, I investigated the associations of childhood infections, IL-6, and CRP with depressive symptoms and psychotic experiences. I showed that a higher burden of common childhood infections is associated with depressive symptoms and psychotic experiences in early and mid-adolescence. In contrast, I discovered that childhood IL-6 and CRP were more strongly associated with subsequent CVD risk than depressive symptoms. CVD risk in adolescence appeared to mediate the relationship between childhood IL-6 or CRP and depressive symptoms in late-adolescence. These results suggest that markers of systemic inflammation in early life have differing associations with depression and CVD risk in young people. I used the UK Biobank to investigate the potential effects of inflammatory markers on comorbid and monomorbid depression and CVD outcomes in middle-aged and older adults. I used both CRP concentration and WCC as exposures. I discovered that CRP and WCC are both associated with depression and ischaemic heart disease (IHD), as well as comorbid depression and IHD. I also showed evidence of specific association between WCC and IHD. These findings suggest that systemic inflammation is likely to be a shared mechanism for depression and IHD, but the risk of each outcome may be underpinned by distinct inflammatory pathways. Taken together, these results indicate that the bidirectional association between CVD and depression is not present until adulthood. While the association between systemic inflammation and depression/CVD appears to be robust, pathophysiological mechanisms for depression and CVD may differ across the lifespan.
Epidemiology, Risk factors, Immunology, Inflammation, Psychiatry, Depression, Cardiovascular disease
Is supplemented by: UK BiobankALSPAC
This record's DOI: https://doi.org/10.17863/CAM.78701
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