Cognitive performance at first episode of psychosis and the relationship with future treatment resistance: Evidence from an international prospective cohort study

The STRATA Consortium, Edward Millgate, Sophie E. Smart, Antonio F. Pardiñas, Eugenia Kravariti, Olesya Ajnakina, Adrianna P. Kępińska, Ole A. Andreassen, Thomas R.E. Barnes, Domenico Berardi, Benedicto Crespo-Facorro, Giuseppe D'Andrea, Arsime Demjaha, Marta Di Forti, Gillian A. Doody, Laura Kassoumeri, Aziz Ferchiou, Lorenzo Guidi, Eileen M. Joyce, Ornella LastrinaIngrid Melle, Baptiste Pignon, Jean Romain Richard, Carmen Simonsen, Andrei Szöke, Ilaria Tarricone, Andrea Tortelli, Javier Vázquez-Bourgon, Robin M. Murray, James T.R. Walters, James H. MacCabe*

*Corresponding author for this work

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Background: Antipsychotic treatment resistance affects up to a third of individuals with schizophrenia, with recent research finding systematic biological differences between antipsychotic resistant and responsive patients. Our aim was to determine whether cognitive impairment at first episode significantly differs between future antipsychotic responders and resistant cases. Methods: Analysis of data from seven international cohorts of first-episode psychosis (FEP) with cognitive data at baseline (N = 683) and follow-up data on antipsychotic treatment response: 605 treatment responsive and 78 treatment resistant cases. Cognitive measures were grouped into seven cognitive domains based on the pre-existing literature. We ran multiple imputation for missing data and used logistic regression to test for associations between cognitive performance at FEP and treatment resistant status at follow-up. Results: On average patients who were future classified as treatment resistant reported poorer performance across most cognitive domains at baseline. Univariate logistic regressions showed that antipsychotic treatment resistance cases had significantly poorer IQ/general cognitive functioning at FEP (OR = 0.70, p = .003). These findings remained significant after adjusting for additional variables in multivariable analyses (OR = 0.76, p = .049). Conclusions: Although replication in larger studies is required, it appears that deficits in IQ/general cognitive functioning at first episode are associated with future treatment resistance. Cognitive variables may be able to provide further insight into neurodevelopmental factors associated with treatment resistance or act as early predictors of treatment resistance, which could allow prompt identification of refractory illness and timely interventions.

Original languageEnglish
Pages (from-to)173-181
Number of pages9
JournalSchizophrenia Research
Early online date29 Mar 2023
Publication statusPublished - May 2023


  • Cognition
  • First episode psychosis
  • Prospective cohort
  • Psychosis
  • Schizophrenia
  • Treatment resistance


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