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

TY - JOUR

T1 - Cognitive performance at first episode of psychosis and the relationship with future treatment resistance

T2 - Evidence from an international prospective cohort study

AU - The STRATA Consortium

AU - Millgate, Edward

AU - Smart, Sophie E.

AU - Pardiñas, Antonio F.

AU - Kravariti, Eugenia

AU - Ajnakina, Olesya

AU - Kępińska, Adrianna P.

AU - Andreassen, Ole A.

AU - Barnes, Thomas R.E.

AU - Berardi, Domenico

AU - Crespo-Facorro, Benedicto

AU - D'Andrea, Giuseppe

AU - Demjaha, Arsime

AU - Di Forti, Marta

AU - Doody, Gillian A.

AU - Kassoumeri, Laura

AU - Ferchiou, Aziz

AU - Guidi, Lorenzo

AU - Joyce, Eileen M.

AU - Lastrina, Ornella

AU - Melle, Ingrid

AU - Pignon, Baptiste

AU - Richard, Jean Romain

AU - Simonsen, Carmen

AU - Szöke, Andrei

AU - Tarricone, Ilaria

AU - Tortelli, Andrea

AU - Vázquez-Bourgon, Javier

AU - Murray, Robin M.

AU - Walters, James T.R.

AU - MacCabe, James H.

N1 - Funding Information: The AESOP (London, UK) cohort was funded by the UK Medical Research Council (Ref: G0500817). The Bologna (Italy) cohort was funded by the European Community's Seventh Framework Program under grant agreement (agreement No. HEALTH-F2-2010–241909, Project EU-GEI). The GAP (London, UK) cohort was funded by the UK National Institute of Health Research (NIHR) Specialist Biomedical Research Centre for Mental Health, South London and Maudsley NHS Mental Health Foundation Trust (SLaM) and the Institute of Psychiatry, Psychology, and Neuroscience at King's College London; Psychiatry Research Trust; Maudsley Charity Research Fund; and the European Community's Seventh Framework Program grant (agreement No. HEALTH-F2-2009-241909, Project EU-GEI). The Oslo (Norway) cohort was funded by the Stiftelsen KG Jebsen, Research Council of Norway (#223273, under the Centers of Excellence funding scheme, and #300309, #283798) and the South-Eastern Norway Regional Health Authority (#2006233, #2006258, #2011085, #2014102, #2015088, #2017-112). The Paris (France) cohort was funded by European Community's Seventh Framework Program grant (agreement No. HEALTH-F2-2010–241909, Project EU-GEI). The Santander (Spain) cohort was funded by the following grants (to B.C.F): Instituto de Salud Carlos III, FIS 00/3095, PI020499, PI050427, PI060507, Plan Nacional de Drogas Research Grant 2005-Orden sco/3246/2004, and SENY Fundatio Research Grant CI 2005-0308007, Fundacion Marques de Valdecilla A/02/07 and API07/011. SAF2016-76046-R and SAF2013-46292-R (MINECO and FEDER). The West London (UK) cohort was funded The Wellcome Trust (Grant Numbers: 042025; 052247; 064607). Funding Information: This work was supported by a Stratified Medicine Programme grant to J.H.M from the Medical Research Council (grant number MR/L011794/1 which funded the research and supported S.E.S., A.F.P., R.M.M., J.T.R.W. & J.H.M.) E.M's PhD is funded by the MRC -doctoral training partnership studentship in Biomedical Sciences at King's College London. J.H.M, E.K, R.M.M are part funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London . A.P.K. is funded by the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. O.A. is further funded by an NIHR Post-Doctoral Fellowship ( PDF-2018-11-ST2-020 ). The views expressed are those of the authors and not necessarily those of the NHS, the MRC, the NIHR or the Department of Health. E.M.J. is supported by the UCL/UCLH Biomedical Research Centre. Publisher Copyright: © 2023

PY - 2023/5

Y1 - 2023/5

N2 - 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.

AB - 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.

KW - Cognition

KW - First episode psychosis

KW - Prospective cohort

KW - Psychosis

KW - Schizophrenia

KW - Treatment resistance

UR - http://www.scopus.com/inward/record.url?scp=85151299604&partnerID=8YFLogxK

U2 - 10.1016/j.schres.2023.03.020

DO - 10.1016/j.schres.2023.03.020

M3 - Article

C2 - 37001392

AN - SCOPUS:85151299604

SN - 0920-9964

VL - 255

SP - 173

EP - 181

JO - Schizophrenia Research

JF - Schizophrenia Research

ER -