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

Velthorst, E.; Mollon, J.; Murray, R. M.; de Haan, L.; Germeys, I. M.; Glahn, D. C.; Arango, C.; van der Ven, E.; Di Forti, M.; Bernardo, M.; Guloksuz, S.; Delespaul, P.; Mezquida, G.; Amoretti, S.; Bobes, J.; Saiz, P. A.; Garcia-Portilla, M. P.; Santos, J. L.; Jimenez-Lopez, E.; Sanjuan, J.; Aguilar, E. J.; Arrojo, M.; Carracedo, A.; Lopez, G.; Gonzalez-Penas, J.; Parellada, M.; Atbasoglu, C.; Saka, M. C.; Ucok, A.; Alptekin, K.; Akdede, B.; Binbay, T.; Altinyazar, V.; Ulas, H.; Yalincetin, B.; Gumus-Akay, G.; Beyaz, B. C.; Soygur, H.; Cankurtaran, E. S.; Kaymak, S. U.; Maric, N. P.; Mihaljevic, M. M.; Petrovic, S. A.; Mirjanic, T.; Del-Ben, C. M.; Ferraro, L.; Gayer-Anderson, C.; Jones, P. B.; Jongsma, H. E.; Kirkbride, J. B.; La Cascia, C.; Lasalvia, A.; Tosato, S.; Llorca, P. -M.; Menezes, P. R.; Morgan, C.; Quattrone, D.; Menchetti, M.; Selten, J. -P.; Szoke, A.; Tarricone, I.; Tortelli, A.; Mcguire, P.; Valmaggia, L.; Kempton, M. J.; van der Gaag, M.; Riecher-Rossler, A.; Bressan, R. A.; Barrantes-Vidal, N.; Nelson, B.; Mcgorry, P.; Pantelis, C.; Krebs, M. -O.; Ruhrmann, S.; Sachs, G.; Rutten, B. P. F.; van Os, J.; Alizadeh, B. Z.; van Amelsvoort, T.; Bartels-Velthuis, A. A.; Bruggeman, R.; van Beveren, N. J.; Luykx, J. J.; Cahn, W.; Simons, C. J. P.; Kahn, R. S.; Schirmbeck, F.; van Winkel, R.; Calem, M.; Tognin, S.; Modinos, G.; Pisani, S.; Kraan, T. C.; van Dam, D. S.; Burger, N.; Amminger, G. P.; Politis, A.; Goodall, J.; Borgwardt, S.; Studerus, E.; Gadelha, A.; Brietzke, E.; Asevedo, G.; Asevedo, E.; Zugman, A.; Dominguez-Martinez, T.; Monsonet, M.; Cristobal-Narvaez, P.; Racioppi, A.; Kwapil, T. R.; Kazes, M.; Daban, C.; Bourgin, J.; Gay, O.; Mam-Lam-Fook, C.; Nordholm, D.; Rander, L.; Krakauer, K.; Glenthoj, L. B.; Glenthoj, B.; Gebhard, D.; Arnhold, J.; Klosterkotter, J.; Lasser, I.; Winklbaur, B.; Reichenberg, A.

doi:10.1038/s41380-020-00969-z

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.