Cognitive functioning and age at onset in non-affective psychotic disorder

van der Werf M, Kohler S, Verkaaik M, Verhey F, van Os J, GROUP Investigators. Cognitive functioning and age at onset in non-affective psychotic disorder. Objective: Age at psychosis onset has been related to variability in cognitive functioning, but its effect may be mediated by demographic and clinical factors. The aim of the current study was to study the contribution of age at onset, as well as demographic and illness characteristics, to variation in cognitive functioning in patients with schizophrenia spectrum disorder. Method: Patients (n = 1053) and healthy controls (n = 631) underwent comprehensive neuropsychological and clinical assessments. The effect of age at onset on age-standardized cognitive test scores was assessed with multiple linear regression analyses. Mediation by illness and demographic factors was tested using a multiple mediation Sobel test. Results: A diagnosis of schizophrenia, higher antipsychotic dose, and more negative symptoms were associated with earlier onset of illness, while female sex and a more chronic course were associated with later illness onset. Furthermore, earlier onset was associated with worse performance on immediate recall and sustained attention. However, male sex, more negative symptoms, and higher antipsychotic dose mediated the effect of age at onset on memory, while negative symptoms explained its association with attention/vigilance. Conclusion: Greater impairment in memory and attention in early-onset psychosis may be explained by features indicative of underlying neurodevelopmental vulnerability.