TY - JOUR
T1 - Cognitive functioning throughout adulthood and illness stages in individuals with psychotic disorders and their unaffected siblings
AU - Velthorst, Eva
AU - Mollon, Josephine
AU - Murray, Robin M.
AU - de Haan, Lieuwe
AU - Germeys, Inez Myin
AU - Glahn, David C.
AU - van der Ven, Els
AU - Arango, Celso
AU - Bernardo, Miguel
AU - Guloksuz, Sinan
AU - Delespaul, Philippe
AU - Mezquida, Gisela
AU - Amoretti, Silvia
AU - Bobes, Julio
AU - Saiz, Pilar A.
AU - García-Portilla, María Paz
AU - Sanjuan, Julio
AU - Aguilar, Eduardo J.
AU - Santos, José Luis
AU - Jiménez-López, Estela
AU - Arrojo, Manuel
AU - Carracedo, Angel
AU - López, Gonzalo
AU - González-Peñas, Javier
AU - Parellada, Mara
AU - Atbaşoğlu, Cem
AU - Saka, Meram Can
AU - Üçok, Alp
AU - Alptekin, Köksal
AU - Akdede, Berna
AU - Binbay, Tolga
AU - Altınyazar, Vesile
AU - Ulaş, Halis
AU - Yalınçetin, Berna
AU - Gümüş-Akay, Güvem
AU - Beyaz, Burçin Cihan
AU - Soygür, Haldun
AU - Cankurtaran, Eylem Şahin
AU - Kaymak, Semra Ulusoy
AU - Maric, Nadja P.
AU - Mihaljevic, Marina M.
AU - Petrovic, Sanja Andric
AU - Mirjanic, Tijana
AU - Del-Ben, Cristina Marta
AU - Di Forti, Marta
AU - Gayer-Anderson, Charlotte
AU - Jones, Peter B.
AU - Jongsma, Hannah E.
AU - Kirkbride, James B.
AU - La Cascia, Caterina
AU - Lasalvia, Antonio
AU - Tosato, Sarah
AU - Llorca, Pierre Michel
AU - Menezes, Paulo Rossi
AU - Morgan, Craig
AU - Quattrone, Diego
AU - Santos, José Luis
AU - Sanjuán, Julio
AU - Selten, Jean Paul
AU - Szoke, Anita
AU - Tarricone, Ilaria
AU - Tortelli, Andrea
AU - McGuire, Philip
AU - Valmaggia, Lucia R.
AU - Kempton, Matthew J.
AU - van der Gaag, Mark
AU - Riecher-Rössler, Anita
AU - Bressan, Rodrigo
AU - Barrantes-Vidal, Neus
AU - Nelson, Barnaby
AU - McGorry, Patrick D.
AU - Pantelis, Christos
AU - Krebs, Marie Odile
AU - Ruhrmann, Stephan
AU - Sachs, Gabriele
AU - Rutten, Bart P.F.
AU - Os, Jim van
AU - Monsonet Bardaji, Manel
N1 - 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.
Funding Information:
Conflict of interest Dr. Arango. has been a consultant to or has received honoraria or grants from Acadia, Angelini, Gedeon Richter, Janssen Cilag, Lundbeck, Minerva, Otsuka, Roche, Sage, Servier, Shire, Schering Plough, Sumitomo Dainippon Pharma, Sunovion and Takeda. Dr. Pantelis has received honoraria for talks at educational meetings and has served on an advisory board for Lundbeck, Australia Pty Ltd. Dr. Bernardo has been a consultant for, received grant/ research support and honoraria from, and been on the speakers/advisory board of ABBiotics, Adamed, Angelini, Casen Recordati, Eli Lilly, Ferrer, Forum Pharmaceuticals, Janssen-Cilag, Lundbeck, Menarini, Otsuka, Takeda and Somatics. MO Krebs received financial support from Janssen, Otsuka Lundbeck alliance, EIsai for educational activities. All other authors report no financial relationships with commercial interests.
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Limited.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/1/7
Y1 - 2021/1/7
N2 - 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.
AB - 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.
KW - SCHIZOPHRENIA-PATIENTS
KW - GENETIC RISK
KW - RELIABILITY
KW - VALIDITY
KW - DEFICITS
KW - IMPAIRMENT
KW - CHILDHOOD
KW - EPISODE
KW - DECLINE
KW - ABILITY
UR - http://www.scopus.com/inward/record.url?scp=85099043499&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/29af395e-4acd-3cc8-b642-8f16d407b6f0/
U2 - 10.1038/s41380-020-00969-z
DO - 10.1038/s41380-020-00969-z
M3 - Artículo
C2 - 33414498
AN - SCOPUS:85099043499
SN - 1359-4184
JO - Molecular Psychiatry (Print)
JF - Molecular Psychiatry (Print)
ER -
