Cognitive subtypes in recent onset psychosis: distinct neurobiological fingerprints?

Research output: Contribution to journalArticlepeer-review


  • the PRONIA consortium

Colleges, School and Institutes

External organisations

  • University of Cologne
  • Icahn School of Medicine at Mount Sinai
  • Ludwig-Maximilians Universität Munchen
  • Max Planck Society
  • Universita degli Studi di Bari
  • IRCCS Eugenio Medea
  • Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico
  • Università degli Studi di Milano and oINFN-Milan
  • Institute for Radiology and Nuclear Medicine St. Anna
  • University of Lübeck
  • Heinrich-Heine-Universität
  • Turku University
  • Birmingham Childrens and Womens Hospital
  • The National Centre of Excellence in Youth Mental Health
  • Centre for Youth Mental Health
  • Max-Planck Institute of Psychiatry
  • King’s College London
  • University of Augsburg
  • Max Planck Institute for Human Cognitive and Brain Sciences


In schizophrenia, neurocognitive subtypes can be distinguished based on cognitive performance and they are associated with neuroanatomical alterations. We investigated the existence of cognitive subtypes in shortly medicated recent onset psychosis patients, their underlying gray matter volume patterns and clinical characteristics. We used a K-means algorithm to cluster 108 psychosis patients from the multi-site EU PRONIA (Prognostic tools for early psychosis management) study based on cognitive performance and validated the solution independently (N = 53). Cognitive subgroups and healthy controls (HC; n = 195) were classified based on gray matter volume (GMV) using Support Vector Machine classification. A cognitively spared (N = 67) and impaired (N = 41) subgroup were revealed and partially independently validated (Nspared = 40, Nimpaired = 13). Impaired patients showed significantly increased negative symptomatology (pfdr = 0.003), reduced cognitive performance (pfdr < 0.001) and general functioning (pfdr < 0.035) in comparison to spared patients. Neurocognitive deficits of the impaired subgroup persist in both discovery and validation sample across several domains, including verbal memory and processing speed. A GMV pattern (balanced accuracy = 60.1%, p = 0.01) separating impaired patients from HC revealed increases and decreases across several fronto-temporal-parietal brain areas, including basal ganglia and cerebellum. Cognitive and functional disturbances alongside brain morphological changes in the impaired subgroup are consistent with a neurodevelopmental origin of psychosis. Our findings emphasize the relevance of tailored intervention early in the course of psychosis for patients suffering from the likely stronger neurodevelopmental character of the disease.

Bibliographic note

Funding Information: This work was supported in analysis and writing of the manuscript by the European Union-FP7 project PRONIA (“Personalized Prognostic Tools for Early Psychosis Management”, grant number 602152). JW was partly supported by the NARSAD Young Investigator Award of LK through the Brain and Behavior Research Foundation (grant number 28474). NK, JK and RKRA are currently honorary speakers for Otsuka/Lundbeck. RU achieved grants from Medical Research Council, grants from the National Institute for Health Research, and personal fees from Sunovion. The remaining authors including members of the PRONIA consortium have nothing to disclose. All procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008. Publisher Copyright: © 2021, The Author(s).


Original languageEnglish
Pages (from-to)1475-1483
Number of pages9
Issue number8
Early online date15 Mar 2021
Publication statusPublished - Jul 2021

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