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

EU-GEI High Risk Study, Eva Velthorst*, Josephine Mollon, 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, Maria Paz Garcia-Portilla, Jose Luis Santos, Estela Jimenez-LopezJulio Sanjuan, Eduardo J. Aguilar, Manuel Arrojo, Angel Carracedo, Gonzalo Lopez, Javier Gonzalez-Penas, Mara Parellada, Cem Atbasoglu, Meram Can Saka, Alp Ucok, Koksal Alptekin, Berna Akdede, Tolga Binbay, Vesile Altinyazar, Halis Ulas, Berna Yalincetin, Guvem Gumus-Akay, Burcin Cihan Beyaz, Haldun Soygur, Eylem Sahin Cankurtaran, Semra Ulusoy Kaymak, Nadja P. Maric, Marina M. Mihaljevic, Sanja Andric Petrovic, Tijana Mirjanic, Cristina Marta Del-Ben, Hannah E. Jongsma, Mark van der Gaag, Behrooz Z. Alizadeh, Agna A. Bartels-Velthuis, Richard Bruggeman

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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
Publication statusPublished - 7-Jan-2021



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