Duration of untreated psychosis and neurocognition in first-episode psychosis: A meta-analysis

Neurocognitive impairment is a well-established feature of first-episode psychosis (FEP). Neurotoxicity hypothesis of psychosis suggests that untreated psychosis before the initiation of first effective treatment is associated with loss of acquired cognitive abilities. However, the outcome of the studies investigating the relationship between duration of untreated psychosis (DUP) and cognitive impairment in FEP remains inconclusive. No previous meta-analysis investigating the relationship between DUP and cognitive impairment in FEP has been published. Following the systematic review of FEP studies, a random-effects meta-analysis of the relationship between DUP and neurocognition in schizophrenia was conducted. Current meta-analysis included 27 studies including 3127 patients with first-episode psychosis. Overall, DUP and cognitive abilities were not significantly related, with the exception of evidence for a weak relationship with a single cognitive domain. There was a very small but significant association between longer DUP and reduced performance in planning/problem-solving ability (r = − 0.09, CI = − 0.14 to − 0.03). Current findings do not provide support for the neurotoxicity hypothesis of psychosis.