Maddock, JM;
(2014)
Vitamin D, common mental disorders and cognition: insights from genetic and observational epidemiology.
Doctoral thesis , UCL (University College London).
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Abstract
The potential relationship between hypovitaminosis D and non-skeletal health outcomes is a growing public health concern. There is suggestion of a relationship between 25-hydroxyvitamin D (25(OH)D) and brain function, with equivocal epidemiological evidence for an association with common mental disorders (CMD) and cognitive function. The aim of the thesis was to investigate the association of 25(OH)D with CMDs and cognitive function in mid-adulthood. Observational and genetic studies were used to gain better insight into the causal nature of the relationship between 25(OH)D and cognitive function. During observational studies, the association of 25(OH)D with CMDs and cognitive function was assessed in the 1958 British birth cohort (1958BC). A genetic study investigated the potential for a gene-environment interaction (GxE) by APOE ε4 on cognitive function using participants from the 1958BC. This GxE study was replicated in an older European cohort. The causal relationship between 25(OH)D and cognitive function was assessed using a Mendelian randomisation (MR) approach in a meta-analyses using participants from nine European cohorts. Using observational data from 1958BC, there was evidence that both low and high 25(OH)D concentrations were associated with increased risk of CMDs and lower memory function. There was also evidence of a GxE interaction for memory function; where increasing 25(OH)D concentrations may be particularly beneficial for those with APOE ε4 genotype. However, results from a MR study provided no evidence for 25(OH)D concentrations acting as a causal factor for cognitive performance in mid- to later-life. Since there was evidence of a non-linear observational association, the MR study may have been underpowered to detect small causal effects at the extremes of the 25(OH)D distribution. Overall, there is some evidence of a potential non-linear association of 25(OH)D with CMDs and cognitive function. However the causal nature of this relationship requires confirmation from large long-term randomised controlled trials.
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