TY - JOUR
T1 - Cognitive subtypes in recent onset psychosis
T2 - distinct neurobiological fingerprints?
AU - the PRONIA consortium
AU - Wenzel, Julian
AU - Haas, Shalaila
AU - Dwyer, Dominic B.
AU - Ruef, Anne
AU - Oeztuerk, Oemer Faruk
AU - Antonucci, Linda A.
AU - von Saldern, Sebastian
AU - Bonivento, Carolina
AU - Garzitto, Marco
AU - Ferro, Adele
AU - Paolini, Marco
AU - Blautzik, Janusch
AU - Borgwardt, Stefan
AU - Brambilla, Paolo
AU - Meisenzahl, Eva
AU - Salokangas, Raimo K.R.
AU - Upthegrove, Rachel
AU - Wood, Stephen J.
AU - Kambeitz, Joseph
AU - Koutsouleris, Nikolaos
AU - Kambeitz-Ilankovic, Lana
AU - Sen Dong, Mark
AU - Erkens, Anne
AU - Gussmann, Eva
AU - Haas, Shalaila
AU - Hasan, Alkomiet
AU - Hoff, Claudius
AU - Khanyaree, Ifrah
AU - Melo, Aylin
AU - Muckenhuber-Sternbauer, Susanna
AU - Kohler, Janis
AU - Oeztuerk, Oemer Faruk
AU - Popovic, David
AU - Penzel, Nora
AU - Rangnick, Adrian
AU - von Saldern, Sebastian
AU - Sanfelici, Rachele
AU - Spangemacher, Moritz
AU - Tupac, Ana
AU - Urquijo, Maria Fernanda
AU - Weiske, Johanna
AU - Wosgien, Antonia
AU - Chisholm, Katharine
AU - Griffiths, Sian Lowri
AU - Iqbal, Mariam
AU - Lalousis, Paris
AU - Pelton, Mirabel
AU - Mallikarjun, Pavan
AU - Stainton, Alexandra
AU - Lin, Ashleigh
N1 - Funding Information:
This work was supported in analysis and writing of the manuscript by the European Union-FP7 project PRONIA (“Personalized Prognostic Tools for Early Psychosis Management”, grant number 602152). JW was partly supported by the NARSAD Young Investigator Award of LK through the Brain and Behavior Research Foundation (grant number 28474). NK, JK and RKRA are currently honorary speakers for Otsuka/Lundbeck. RU achieved grants from Medical Research Council, grants from the National Institute for Health Research, and personal fees from Sunovion. The remaining authors including members of the PRONIA consortium have nothing to disclose. All procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/7
Y1 - 2021/7
N2 - In schizophrenia, neurocognitive subtypes can be distinguished based on cognitive performance and they are associated with neuroanatomical alterations. We investigated the existence of cognitive subtypes in shortly medicated recent onset psychosis patients, their underlying gray matter volume patterns and clinical characteristics. We used a K-means algorithm to cluster 108 psychosis patients from the multi-site EU PRONIA (Prognostic tools for early psychosis management) study based on cognitive performance and validated the solution independently (N = 53). Cognitive subgroups and healthy controls (HC; n = 195) were classified based on gray matter volume (GMV) using Support Vector Machine classification. A cognitively spared (N = 67) and impaired (N = 41) subgroup were revealed and partially independently validated (Nspared = 40, Nimpaired = 13). Impaired patients showed significantly increased negative symptomatology (pfdr = 0.003), reduced cognitive performance (pfdr < 0.001) and general functioning (pfdr < 0.035) in comparison to spared patients. Neurocognitive deficits of the impaired subgroup persist in both discovery and validation sample across several domains, including verbal memory and processing speed. A GMV pattern (balanced accuracy = 60.1%, p = 0.01) separating impaired patients from HC revealed increases and decreases across several fronto-temporal-parietal brain areas, including basal ganglia and cerebellum. Cognitive and functional disturbances alongside brain morphological changes in the impaired subgroup are consistent with a neurodevelopmental origin of psychosis. Our findings emphasize the relevance of tailored intervention early in the course of psychosis for patients suffering from the likely stronger neurodevelopmental character of the disease.
AB - In schizophrenia, neurocognitive subtypes can be distinguished based on cognitive performance and they are associated with neuroanatomical alterations. We investigated the existence of cognitive subtypes in shortly medicated recent onset psychosis patients, their underlying gray matter volume patterns and clinical characteristics. We used a K-means algorithm to cluster 108 psychosis patients from the multi-site EU PRONIA (Prognostic tools for early psychosis management) study based on cognitive performance and validated the solution independently (N = 53). Cognitive subgroups and healthy controls (HC; n = 195) were classified based on gray matter volume (GMV) using Support Vector Machine classification. A cognitively spared (N = 67) and impaired (N = 41) subgroup were revealed and partially independently validated (Nspared = 40, Nimpaired = 13). Impaired patients showed significantly increased negative symptomatology (pfdr = 0.003), reduced cognitive performance (pfdr < 0.001) and general functioning (pfdr < 0.035) in comparison to spared patients. Neurocognitive deficits of the impaired subgroup persist in both discovery and validation sample across several domains, including verbal memory and processing speed. A GMV pattern (balanced accuracy = 60.1%, p = 0.01) separating impaired patients from HC revealed increases and decreases across several fronto-temporal-parietal brain areas, including basal ganglia and cerebellum. Cognitive and functional disturbances alongside brain morphological changes in the impaired subgroup are consistent with a neurodevelopmental origin of psychosis. Our findings emphasize the relevance of tailored intervention early in the course of psychosis for patients suffering from the likely stronger neurodevelopmental character of the disease.
UR - http://www.scopus.com/inward/record.url?scp=85108386903&partnerID=8YFLogxK
U2 - 10.1038/s41386-021-00963-1
DO - 10.1038/s41386-021-00963-1
M3 - Article
C2 - 33723384
AN - SCOPUS:85108386903
SN - 0893-133X
VL - 46
SP - 1475
EP - 1483
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
IS - 8
ER -
