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

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 Lastrina; Ingrid 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; STRATA Consortium

doi:10.1016/j.schres.2023.03.020

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

Schizophr Res. 2023 May:255:173-181. doi: 10.1016/j.schres.2023.03.020. Epub 2023 Mar 29.

Authors

Edward Millgate¹, Sophie E Smart², Antonio F Pardiñas², Eugenia Kravariti¹, Olesya Ajnakina³, Adrianna P Kępińska¹, Ole A Andreassen⁴, Thomas R E Barnes⁵, Domenico Berardi⁶, Benedicto Crespo-Facorro⁷, Giuseppe D'Andrea⁶, Arsime Demjaha¹, Marta Di Forti⁸, Gillian A Doody⁹, Laura Kassoumeri¹, Aziz Ferchiou¹⁰, Lorenzo Guidi¹¹, Eileen M Joyce¹², Ornella Lastrina¹¹, Ingrid Melle⁴, Baptiste Pignon¹⁰, Jean-Romain Richard¹³, Carmen Simonsen¹⁴, Andrei Szöke¹⁰, Ilaria Tarricone¹¹, Andrea Tortelli¹⁵, Javier Vázquez-Bourgon¹⁶, Robin M Murray¹, James T R Walters², James H MacCabe¹⁷; STRATA Consortium

Affiliations

¹ Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
² MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
³ Department of Biostatistics & Health Informatics, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; Department of Behavioural Science and Health, Institute of Epidemiology and Health Care, University College London, London, UK.
⁴ Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
⁵ Division of Psychiatry, Imperial College London, UK.
⁶ Department of Biomedical and Neuro-motor Sciences, Psychiatry Unit, Alma Mater Studiorum Università di Bologna, Bologna, Italy.
⁷ Department of Psychiatry, Hospital Universitario Virgen del Rocio, IBiS, Universidad de Sevilla, Spain; Centro de Investigacion en Red Salud Mental (CIBERSAM), Sevilla, Spain.
⁸ Social Genetics and Developmental Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; South London and Maudsley NHS Mental Health Foundation Trust, London, UK.
⁹ Department of Medical Education, University of Nottingham Faculty of Medicine and Health Sciences, Nottingham, UK.
¹⁰ Univ Paris Est Creteil, INSERM, IMRB, Translational Neuropsychiatry, Fondation FondaMental, Creteil, France; AP-HP, Hôpitaux Universitaires H. Mondor, DMU IMPACT, FHU ADAPT, Creteil, France.
¹¹ Department of Medical and Surgical Sciences, Bologna Transcultural Psychosomatic Team (BoTPT), Alma Mater Studiorum - University of Bologna, Bologna, Italy.
¹² Department of Clinical and Movement Neuroscience, UCL Queen Square Institute of Neurology, University College London, London, UK.
¹³ Univ Paris Est Creteil, INSERM, IMRB, Translational Neuropsychiatry, Fondation FondaMental, Creteil, France.
¹⁴ Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Early Intervention in Psychosis Advisory Unit for South East Norway (TIPS Sør-Øst), Division of Mental Health and Addiction, Oslo University Hospital, Norway.
¹⁵ Univ Paris Est Creteil, INSERM, IMRB, Translational Neuropsychiatry, Fondation FondaMental, Creteil, France; Groupe Hospitalier Universitaire Psychiatrie Neurosciences Paris, Pôle Psychiatrie Précarité, Paris, France.
¹⁶ Centro de Investigacion en Red Salud Mental (CIBERSAM), Sevilla, Spain; Department of Psychiatry, University Hospital Marques de Valdecilla - Instituto de Investigación Marques de Valdecilla (IDIVAL), Santander, Spain; Department of Medicine and Psychiatry, School of Medicine, University of Cantabria, Santander, Spain.
¹⁷ Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; South London and Maudsley NHS Mental Health Foundation Trust, London, UK. Electronic address: james.maccabe@kcl.ac.uk.

Abstract

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.

Keywords: Cognition; First episode psychosis; Prospective cohort; Psychosis; Schizophrenia; Treatment resistance.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antipsychotic Agents* / therapeutic use
Cognition
Humans
Prospective Studies
Psychotic Disorders* / complications
Psychotic Disorders* / drug therapy
Psychotic Disorders* / psychology
Schizophrenia* / complications
Schizophrenia* / drug therapy

Substances

Antipsychotic Agents

Abstract

Publication types

MeSH terms

Substances

Grants and funding