Meta-analysis of cognitive deficits in ultra-high risk to psychosis and first-episode psychosis: do the cognitive deficits progress over, or after, the onset of psychosis?

Cognitive dysfunction is a well-established feature of schizophrenia, and there is evidence suggesting that cognitive deficits are secondary to abnormal neurodevelopment leading to problems in acquiring such abilities. However, it is not clear whether there is also a decline in cognitive performance over, or after, the onset of psychosis. Our objective was to quantitatively examine the longitudinal changes in cognitive function in patients who presented with first-episode psychosis (FEP), ultra-high risk (UHR) for psychosis, and controls. Electronic databases were searched for the studies published between January 1987 and February 2013. All studies reporting longitudinal cognitive data in FEP and UHR subjects were retrieved. We conducted meta-analyses of 25 studies including 905 patients with FEP, 560 patients at UHR, and 405 healthy controls. The cognitive performances of FEP, UHR, and healthy controls all significantly improved over time. There was no publication bias, and distributions of effect sizes were very homogenous. In FEP, the degree of improvement in verbal working memory and executive functions was significantly associated with reduction in negative symptoms. There was no evidence of cognitive decline in patients with UHR and FEP. In contrast, the cognitive performances of both groups improved at follow-up. These findings suggest that cognitive deficits are already established before the prodromal phases of psychosis. These data support the neurodevelopmental model rather than neurodegenerative and related staging models of schizophrenia.