THE ASSOCIATIONS AMONG HISTORY OF PSYCHOSIS, NEUROPSYCHOLOGICAL PERFORMANCE, AND FUNCTIONING IN REMITTED LATER-LIFE MAJOR DEPRESSION

Abstract

Introduction Observational studies report that people with psychotic major depressive disorder (PMD) have poorer functional outcome than those with 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 those with PMD than NPMD, both acutely and in remission. The aim of this study was to examine the relative contributions of a history of psychosis and neuropsychological performance to impaired everyday function in patients with remitted later-life major depressive disorder (MDD). We hypothesized that, in later-life patients with MDD, a history of psychotic features and poorer neuropsychological function would be independently associated with poorer everyday functioning, but that poorer neuropsychological performance would be more strongly associated with poorer functioning compared to history of psychosis. In order to place the results in a broader context, we examined everyday functioning in an age- and gender-matched non-psychiatric comparison group. Methods This cross-sectional design study included 73 patients aged 50 years and older with a history of MDD (n = 51 with NPMD and n = 22 with PMD) in sustained remission and 42 non-psychiatric comparison subjects. Sociodemographic, clinical, neuropsychological, and functional data were collected by an investigator blind to the history of psychotic features. Everyday functioning, the dependent variable, was divided into general functioning (measured by participant-report) and IADL performance (measured by observer-rated assessment). The independent variables were i) history of psychosis and ii) neuropsychological performance in the domains of processing speed, memory, and executive function. Relationships between each independent variable and functioning were analyzed using multiple linear regression models. The relative contribution of history of psychosis and neuropsychological performance to functioning was analyzed using multiple regression models with history of psychosis entered in the first step and the neuropsychological variable in the second step. All models included covariates that were potential confounders. We also calculated effect sizes for the difference in functioning between MDD and non-psychiatric comparison participants. Results Patients with PMD exhibited substantial deficits in measures of processing speed and, to a lesser extent, executive function, compared to NPMD patients and to population norms. History of psychosis was independently related to poorer IADL performance (β = 0.262, t = 3.03, p = 0.004) and general functioning (β = -0.29, t = -2.46, p = 0.017). Poorer performance on measures of processing speed (β = -0.468, t = -4.99, p In comparison to non-psychiatric subjects, the effect size of functional impairment in patients with remitted PMD was large (Cohen's d for IADL function = 0.80; Cohen's d for general functioning = 0.97), whereas the impairment was small to moderate in remitted NPMD (Cohen's d for IADL function = 0.10; Cohen's d for general functioning = 0.64). Conclusions Later-life remitted PMD is associated with poorer everyday functioning compared to NPMD, with clinically-significant deficits. However, this relationship is no longer significant when neuropsychological function, especially processing speed, is accounted for. This study advances previous literature by including only patients with rigorously-defined sustained remission and measuring functioning comprehensively using both participant-report and performance-based measures. We will discuss future directions of these research findings, including examining neurobiological correlates of processing speed deficits in remitted PMD. This research was funded by This study was funded by the University Health Network Centre for Mental Health's research grant ($14,000)