Cognitive function in people with psychiatric and neurological disorders in UK Biobank

Cognitive impairment is a major cause of disability for a large number of working-age adults living with chronic psychiatric and neurological conditions. Although well recognised in schizophrenia spectrum disorders and in neurological diseases such as multiple sclerosis (MS), cognitive impairment has historically received less attention in mood disorders. The relative prevalence of cognitive impairment in bipolar disorder (BD) and major depression compared with other conditions has not been clearly established, and the risk factors that drive cognitive variation within and across conditions are not well understood. The primary focus of this thesis was on BD, and the objectives were: (1) to investigate the prevalence of cognitive impairment in BD, compared with major depression, schizophrenia, MS and Parkinson’s disease (PD); and (2) to develop causal models to quantify and explain variation in cognitive function in BD and in other conditions. The methods encompassed a systematic literature review, a prevalence study using cross-sectional data from the UK Biobank cohort, and a series of multivariable analyses of UK Biobank data using graphical methods, regression- and matching-based estimation, and mediation models. The systematic review indicated that between 5% and 58% of adults with euthymic BD showed cognitive impairment. Prevalence was lower in the mania/BD group identified within the UK Biobank cohort, at around 7-10%, which was similar to rates seen in the MS and PD groups within the cohort. When causal models of cognitive performance in the mania/BD group took account of multiple potential confounders, performance on a short-term visuospatial memory test showed a small but reliable decrement. Mediation models provided evidence of indirect negative effects on cognitive performance via psychotropic medication, but not via cardiometabolic disease. A similar pattern of results was seen in the major depression group, though with smaller effect sizes. This thesis emphasises the importance of cognitive function as a fundamental phenotype in psychiatric and epidemiological research. There is scope to build on this work in future follow-up waves in UK Biobank, as well as in other UK and international cohort studies and through linkage with routine healthcare data.