The Associations between History of Psychosis, Neuropsychological Performance and Functioning in Remitted Later-life Major Depression

Observational studies report that psychotic major depressive disorder (PMD) has poorer functional outcome than non-psychotic major depression (NPMD), but this finding could be explained by less robust recovery and residual symptoms in PMD. In addition, neuropsychological performance is worse in PMD than NPMD, both acutely and in remission. The overarching goal of this research is to examine the relative contributions of a history of psychosis and neuropsychological performance to impaired everyday function in remitted major depressive disorder (MDD). This thesis examined this question via three projects. The first investigated the optimal method to assess functioning in later-life depression through a systematic review of existing assessment instruments. Two instruments, the Performance Assessment of Self-Care Skills and the Late-Life Function and Disability Instrument, were best suited to our measurement needs. In our second and main project, we examined whether history of psychosis is associated with poorer everyday functioning in remitted later-life MDD and, if so, whether this relationship is explained by neuropsychological performance. As hypothesized, history of psychotic features and poorer neuropsychological performance each independently predicted worse functioning, but the association was much stronger for neuropsychological performance, especially processing speed. In comparison to an age and gender-matched group with no history of psychiatric disorder, the effect size of functional impairment in patients with remitted PMD was large, whereas the impairment was small to moderate in NPMD. In our third project, we explored a potential mechanism for vulnerability to psychosis and neuropsychological and functional deficits in depression: sustained hypercortisolemia, measured using hair cortisol concentration and analysed with correlation coefficients. We found no clinically significant relationship between cortisol and history of psychosis, cognition or functioning. To further investigate the mechanism of impaired neuropsychological performance and function in remitted PMD, we propose a line of research examining the microstructure and function of brain white matter.Ph.D.2020-10-30 00:00:0