Trajectories of Cognitive Function in First-Episode Psychosis: Associations to Clinical Outcomes and Biomarkers

Abstract

Aims: Cognitive dysfunction in psychotic disorders is common. At disorder onset, this impairment varies greatly between individuals, which may reflect different levels of decline compared to pre-morbid levels. Diverse trajectories in cognitive change prior to psychosis onset have been hypothesized to represent different underlying pathological processes. Our primary aim was to model cognitive change over time in a sample of individuals with first-episode psychosis (FEP) and controls. The secondary aim was to explore whether cognitive change was associated with clinical outcomes, and biological markers that have shown associations with disease progression. Methods: Our sample consisted of 73 individuals with FEP who had undergone cognitive assessment at psychosis onset and 53 controls. Using school grades from registry data as a proxy for pre-morbid cognitive ability, we modelled change in cognition using linear mixed-effects models. The resulting change scores were correlated to polygenic risk scores, cerebrospinal fluid levels of complement protein C4A and clinical outcomes. Results and Conclusions: Groups did not differ in school performance prior to psychosis. Psychosis onset was associated with a large cognitive decline in FEP and thereafter they performed significantly worse than controls. Among FEP individuals, there was a large degree of variability in cognitive change leading up to psychosis onset. Degree of cognitive change was not associated to the selected biological variables but did predict worse clinical outcomes. The results indicate that individual cognitive trajectories may be a clinically relevant topic for further study, but given the exploratory nature of the analysis, replication in an independent sample is required.