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

Eva Velthorst*, Josephine Mollon, Robin M. Murray, Lieuwe de Haan, Inez Myin Germeys, David C. Glahn, Els van der Ven, Celso Arango, Miguel Bernardo, Sinan Guloksuz, Philippe Delespaul, Gisela Mezquida, Silvia Amoretti, Julio Bobes, Pilar A. Saiz, María Paz García-Portilla, Julio Sanjuan, Eduardo J. Aguilar, José Luis Santos, Estela Jiménez-LópezManuel 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, Marta Di Forti, Charlotte Gayer-Anderson, Peter B. Jones, Hannah E. Jongsma, James B. Kirkbride, Caterina La Cascia, Antonio Lasalvia, Sarah Tosato, Pierre Michel Llorca, Paulo Rossi Menezes, Craig Morgan, Diego Quattrone, José Luis Santos, Julio Sanjuán, Jean Paul Selten, Anita Szoke, Ilaria Tarricone, Andrea Tortelli, Philip McGuire, Lucia R. Valmaggia, Matthew J. Kempton, Mark van der Gaag, Anita Riecher-Rössler, Rodrigo Bressan, Neus Barrantes-Vidal, Barnaby Nelson, Patrick D. McGorry, Christos Pantelis, Marie Odile Krebs, Stephan Ruhrmann, Gabriele Sachs, Bart P.F. Rutten, Jim van Os*, , Manel Monsonet Bardaji

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

2 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 languageAmerican English
Number of pages15
JournalMolecular Psychiatry
Early online date7 Jan 2021
Publication statusPublished - 7 Jan 2021




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