Cognition before and after psychosis onset: A naturalistic study of change, heterogeneity, and prognosis.

Aims: Cognitive dysfunction is a core feature of psychotic disorders. The degree of impairment varies greatly between individuals, which may reflect different levels of decline from pre-morbid functioning. Diverse trajectories of cognitive change prior to or during development of psychosis have been hypothesized to reflect distinct 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 associations between cognitive change, clinical outcomes and select biological markers. Methods: Our sample consisted of 72 individuals with FEP and 53 controls. School grades from nationwide population registers were used as a proxy for pre-morbid cognitive ability. All participants underwent formal cognitive testing at psychosis onset, with a subset returning for testing at 1,5 year follow up. Cognitive change was modelled using linear mixed-effects models, and resulting change scores were correlated to polygenic risk scores, cerebrospinal fluid levels of complement protein C4A and clinical outcomes. Results: Groups did not differ in school performance prior to psychosis. Psychosis onset was associated with marked cognitive decline in FEP individuals, who subsequently performed significantly worse than controls. However, cognitive change over time varied widely between FEP individuals. Degree of cognitive change was not associated with the selected biological variables but did predict worse clinical outcomes. Conclusions: Individual cognitive trajectories may be a clinically relevant topic for further study, and larger studies are needed to further explore their potential role in stratified models of care.