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

E. Velthorst*, J. Mollon, R.M. Murray, L. de Haan, I.M. Germeys, D.C. Glahn, C. Arango, E. van der Ven, M. Di Forti, M. Bernardo, S. Guloksuz, P. Delespaul, G. Mezquida, S. Amoretti, J. Bobes, P.A. Saiz, M.P. Garcia-Portilla, J.L. Santos, E. Jimenez-Lopez, J. SanjuanE.J. Aguilar, M. Arrojo, A. Carracedo, G. Lopez, J. Gonzalez-Penas, M. Parellada, C. Atbasoglu, M.C. Saka, A. Ucok, K. Alptekin, B. Akdede, T. Binbay, V. Altinyazar, H. Ulas, B. Yalincetin, G. Gumus-AkaY, B.C. Beyaz, H. Soygur, E.S. Cankurtaran, S.U. Kaymak, N.P. Maric, M.M. Mihaljevic, S.A. Petrovic, T. Mirjanic, C.M. Del-Ben, L. Ferraro, C. Gayer-Anderson, P.B. Jones, H.E. Jongsma, J.B. Kirkbride, Claudia Simons, Ruud van Winkel, EU-GEI High Risk Study

*Corresponding author for this work

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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
Issue number8
Early online date7 Jan 2021
Publication statusPublished - Aug 2021


  • ability
  • childhood
  • decline
  • deficits
  • episode
  • genetic risk
  • impairment
  • reliability
  • schizophrenia-patients
  • validity

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