Cognitive subtypes in recent onset psychosis: distinct neurobiological fingerprints?
Authors: Wenzel Julian , Haas Shalaila S. , Dwyer Dominic B. , Ruef Anne , Oeztuerk Oemer Faruk , Antonucci Linda A. , von Saldern Sebastian , Bonivento Carolina , Garzitto Marco , Ferro Adele , Paolini Marco , Blautzik Janusch , Borgwardt Stefan , Brambilla Paolo , Meisenzahl Eva , Salokangas Raimo K. R. , Upthegrove Rachel , Wood Stephen J. , Kambeitz Joseph , Koutsouleris Nikolaos , Kambeitz-Ilankovic Lana ,   the PRONIA consortium, Sen Dong Mark , Erkens Anne , Gussmann Eva , Haas Shalaila , Hasan Alkomiet , Hoff Claudius , Khanyaree Ifrah , Melo Aylin , Muckenhuber-Sternbauer Susanna , Kohler Janis , Oeztuerk Oemer Faruk , Popovic David , Penzel Nora , Rangnick Adrian , von Saldern Sebastian , Sanfelici Rachele , Spangemacher Moritz , Tupac Ana , Urquijo Maria Fernanda , Weiske Johanna , Wosgien Antonia , Ruhrmann Stephan , Rosen Marlene , Betz Linda , Haidl Theresa , Blume Karsten , Seves Mauro , Kaiser Nathalie , Pilgram Tanja , Lichtenstein Thorsten , Woopen Christiane , Borgwardt Stefan , Andreou Christina , Egloff Laura , Harrisberger Fabienne , Lenz Claudia , Leanza Letizia , Mackintosh Amatya , Smieskova Renata , Studerus Erich , Walter Anna , Widmayer Sonja , Chisholm Katharine , Day Chris , Griffiths Sian Lowri , Iqbal Mariam , Lalousis Paris , Pelton Mirabel , Mallikarjun Pavan , Stainton Alexandra , Lin Ashleigh , Denissoff Alexander , Ellila Anu , Tiina From R. N. , Heinimaa Markus , Ilonen Tuula , Jalo Paivi , Heikki Laurikainen R. N. , Lehtinen Maarit , Antti Luutonen R. N. , Makela Akseli , Paju Janina , Pesonen Henri , Armio Reetta-Liina , Sormunen Elina , Toivonen Anna , Turtonen Otto , Solana Ana Beatriz , Abraham Manuela , Hehn Nicolas , Schirmer Timo , Altamura Carlo , Belleri Marika , Bottinelli Francesca , Re Marta , Monzani Emiliano , Percudani Mauro , Sberna Maurizio , D’Agostino Armando , Del Fabro Lorenzo , Menni Villa San Benedetto , Perna Giampaolo , Nobile Maria , Alciati Alessandra , Balestrieri Matteo , Cabras Giuseppe , Fabbro Franco , Piccin Sara , Bertolino Alessandro , Blasi Giuseppe , Antonucci Linda A. , Pergola Giulio , Caforio Grazia , Faio Leonardo , Quarto Tiziana , Gelao Barbara , Romano Raffaella , Andriola Ileana , Falsetti Andrea , Barone Marina , Passatiore Roberta , Sangiuliano Marina , Lencer Rebekka , Surman Marian , Bienek Olga , Romer Georg , Dannlowski Udo , Schultze-Lutter Frauke , Schmidt-Kraepelin Christian , Neufang Susanne , Korda Alexandra , Rohner Henrik 
Published: March 2021

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.