Cognitive functioning throughout adulthood and illness stages in individuals with psychotic disorders and their unaffected siblings

Eva Velthorst*, Josephine Mollon, EU-GEI High Risk Study, Robin M. Murray, Lieuwe de Haan, Inez Myin Germeys, David C. Glahn, Celso Arango, Els van der Ven, Marta Di Forti, Miguel Bernardo, Sinan Guloksuz, Philippe Delespaul, Gisela Mezquida, Silvia Amoretti, Julio Bobes, Pilar A. Saiz, María Paz García-Portilla, José Luis Santos, Estela Jiménez-LópezJulio Sanjuan, Eduardo J. Aguilar, Manuel Arrojo, Angel Carracedo, Gonzalo López, Javier González-Peñas, Mara Parellada, Cem Atbaşoğlu, Meram Can Saka, Alp Üçok, Köksal Alptekin, Berna Akdede, Tolga Binbay, Vesile Altınyazar, Halis Ulaş, Berna Yalınçetin, Güvem Gümüş-Akay, Burçin Cihan Beyaz, Haldun Soygür, Eylem Şahin Cankurtaran, Semra Ulusoy Kaymak, Nadja P. Maric, Marina M. Mihaljevic, Sanja Andric Petrovic, Tijana Mirjanic, Cristina Marta Del-Ben, Laura Ferraro, Charlotte Gayer-Anderson, Peter B. Jones, Hannah E. Jongsma, James B. Kirkbride, Nico Van Beveren, Ruud van Winkel, A Reichenberg

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

13 Citations (Scopus)


Important questions remain about the profile of cognitive impairment in psychotic disorders across adulthood and illness stages. The age-associated profile of familial impairments also remains unclear, as well as the effect of factors, such as symptoms, functioning, and medication. Using cross-sectional data from the EU-GEI and GROUP studies, comprising 8455 participants aged 18 to 65, we examined cognitive functioning across adulthood in patients with psychotic disorders (n = 2883), and their unaffected siblings (n = 2271), compared to controls (n = 3301). An abbreviated WAIS-III measured verbal knowledge, working memory, visuospatial processing, processing speed, and IQ. Patients showed medium to large deficits across all functions (ES range = –0.45 to –0.73, p < 0.001), while siblings showed small deficits on IQ, verbal knowledge, and working memory (ES = –0.14 to –0.33, p < 0.001). Magnitude of impairment was not associated with participant age, such that the size of impairment in older and younger patients did not significantly differ. However, first-episode patients performed worse than prodromal patients (ES range = –0.88 to –0.60, p < 0.001). Adjusting for cannabis use, symptom severity, and global functioning attenuated impairments in siblings, while deficits in patients remained statistically significant, albeit reduced by half (ES range = –0.13 to –0.38, p < 0.01). Antipsychotic medication also accounted for around half of the impairment in patients (ES range = –0.21 to –0.43, p < 0.01). Deficits in verbal knowledge, and working memory may specifically index familial, i.e., shared genetic and/or shared environmental, liability for psychotic disorders. Nevertheless, potentially modifiable illness-related factors account for a significant portion of the cognitive impairment in psychotic disorders.

Original languageEnglish
Pages (from-to)4529-4543
Number of pages15
JournalMolecular Psychiatry
Issue number8
Early online date7 Jan 2021
Publication statusPublished - Aug 2021

Bibliographical note

Funding Information:
Acknowledgements The European Community’s Seventh Framework Programme under grant agreement No. HEALTH-F2-2010-241909 (EU-GEI). The Geestkracht programme of the Dutch Health Research Council (Zon-Mw)(GROUP). Dr. Velthorst is supported by The Seaver Foundation. Dr. Pantelis was supported by a NHMRC Senior Principal Research Fellowship (ID: 1105825), a NHMRC Program Grant (ID: 1150083). The Melbourne arm of the study was supported by a grant from the Australian National Health & Medical Research Council (NHMRC-EU grant ID: 567215). The French cohort was supported by the French Ministry grant (PHRC ICAAR - AOM07-118). The Spanish sample was supported by the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (SAM16PE07CP1, PI16/02012, PI19/024), Madrid Regional Government (B2017/BMD-3740 AGES-CM-2), Fundación Familia Alonso and Fundación Alicia Koplowitz. The Brazilian sample was supported by FAPESP-Brazil (grant 2012/05178-0). Additional support was provided by a Medical Research Council Fellowship to Dr. Kempton (grant MR/ J008915/1). Dr. Kirkbride was supported by the National Institute for Health Research University College London Hospital Biomedical Research Centre. Dr. Nelson was supported by an NHMRC Senior Research Fellowship (1137687). We would like to thank the EU-GEI WP2 Group not mentioned in main author list: Kathryn Hubbard, Stephanie Beards, Simona A. Stilo, Pedro Cuadrado, José Juan Rodríguez Solano, David Fraguas, Álvaro Andreu-Bernabeu, Gonzalo López, Bibi-ana Cabrera, Juan Nacher, Javier Costas, Mario Matteis [8], Marta Rapado-Castro, Emiliano González, Covadonga M. Díaz-Caneja [8], Emilio Sánchez, Manuel Durán-Cutilla, Nathalie Franke, Fabian Ter-morshuizen, Daniella van Dam, Elles Messchaart, Marion Leboyer [4], Franck Schurḧ off, Stéphane Jamain, Grégoire Baudin, Aziz Ferchiou, Baptiste Pignon, Jean-Romain Richard, Thomas Charpeaud, Anne-Marie Tronche, Flora Frijda, Giovanna Marrazzo, Crocettarachele Sartorio, Fabio Seminerio, Camila Marcelino Loureiro, Rosana Shuhama, Mirella Ruggeri, Chiara Bonetto, Doriana Cristofalo, Domenico Berardi, Marco Seri, Elena Bonora, Anastasios Nougus, Giuseppe D’Andrea, Laura Ferraro, Giada Tripoli, Ulrich Reininghaus, Enrique García Bernardo, Laura Roldán, Esther Lorente-Rovira, Ma Soledad Olmeda, Daniele La Barbera, Cristina M. Del-Ben, Lucia Sideli. Study funders contributed to the salaries of the research workers employed, but did not participate in the study design, data analyses, data interpretation, or writing of the manuscript. All authors had full access to the study data and had final responsibility for the decision to submit for publication.

Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Limited.


Dive into the research topics of 'Cognitive functioning throughout adulthood and illness stages in individuals with psychotic disorders and their unaffected siblings'. Together they form a unique fingerprint.

Cite this