Transdiagnostic subgroups of cognitive impairment in early affective and psychotic illness
Authors: Wenzel Julian , Badde Luzie , Haas Shalaila S. , Bonivento Carolina , Van Rheenen Tamsyn E. , Antonucci Linda A. , Ruef Anne , Penzel Nora , Rosen Marlene , Lichtenstein Theresa , Lalousis Paris Alexandros , Paolini Marco , Stainton Alexandra , Dannlowski Udo , Romer Georg , Brambilla Paolo , Wood Stephen J. , Upthegrove Rachel , Borgwardt Stefan , Meisenzahl Eva , Salokangas Raimo K. R. , Pantelis Christos , Lencer Rebekka , Bertolino Alessandro , Kambeitz Joseph , Koutsouleris Nikolaos , Dwyer Dominic B. , Kambeitz-Ilankovic Lana ,   the PRONIA consortium, Dong Mark Sen , Erkens Anne , Gussmann Eva , Haas Shalaila , Hasan Alkomiet , Hoff Claudius , Khanyaree Ifrah , Melo Aylin , Muckenhuber-Sternbauer Susanna , Kohler Janis , Ozturk Omer Faruk , Popovic David , Rangnick Adrian , von Saldern Sebastian , Sanfelici Rachele , Spangemacher Moritz , Tupac Ana , Urquijo Maria Fernanda , Weiske Johanna , Wosgien Antonia , Ruhrmann Stephan , Betz Linda , Blume Karsten , Seves Mauro , Kaiser Nathalie , Pilgram Tanja , Lichtenstein Thorsten , Woopen Christiane , Schmidt André , Riecher-Rössler Anita , 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 , Pelton Mirabel , Mallikarjun Pavan , Lin Ashleigh , Denissoff Alexander , Ellila Anu , From Tiina , Heinimaa Markus , Ilonen Tuula , Jalo Paivi , Laurikainen Heikki , Lehtinen Maarit , Luutonen Antti , Makela Akseli , Paju Janina , Pesonen Henri , Armio Reetta-Liina , Sormunen Elina , Toivonen Anna , Turtonen Otto , Hietala Jarmo , Kolkka Mirka , Luutonen Sinikka , Walta Maija , Tuominen Lauri , Solana Ana Beatriz , Abraham Manuela , Hehn Nicolas , Schirmer Timo , Altamura Carlo , Belleri Marika , Bottinelli Francesca , Ferro Adele , Re Marta , Monzani Emiliano , Percudani Mauro , Sberna Maurizio , D’Agostino Armando , Del Fabro Lorenzo , Perna Giampaolo , Nobile Maria , Alciati Alessandra , Balestrieri Matteo , Cabras Giuseppe , Fabbro Franco , Garzitto Marco , Piccin Sara , Blasi Giuseppe , Pergola Giulio , Caforio Grazia , Facio Leonardo , Quarto Tiziana , Gelao Barbara , Romano Raffaella , Andriola Ileana , Falsetti Andrea , Barone Marina , Passatiore Roberta , Sangiuliano Marina , Surman Marian , Bienek Olga , Schultze-Lutter Frauke , Schmidt-Kraepelin Christian , Neufang Susanne , Korda Alexandra , Rohner Henrik 
Published: September 2023

Cognitively impaired and spared patient subgroups were identified in psychosis and depression, and in clinical high-risk for psychosis (CHR). Studies suggest differences in underlying brain structural and functional characteristics. It is unclear whether cognitive subgroups are transdiagnostic phenomena in early stages of psychotic and affective disorder which can be validated on the neural level. Patients with recent-onset psychosis (ROP;N = 140; female = 54), recent-onset depression (ROD;N = 130; female = 73), CHR (N = 128; female = 61) and healthy controls (HC;N = 270; female = 165) were recruited through the multi-site study PRONIA. The transdiagnostic sample and individual study groups were clustered into subgroups based on their performance in eight cognitive domains and characterized by gray matter volume (sMRI) and resting-state functional connectivity (rsFC) using support vector machine (SVM) classification. We identified an impaired subgroup (NROP = 79,NROD = 30,NCHR = 37) showing cognitive impairment in executive functioning, working memory, processing speed and verbal learning (allp < 0.001). A spared subgroup (NROP = 61,NROD = 100,NCHR = 91) performed comparable to HC. Single-disease subgroups indicated that cognitive impairment is stronger pronounced in impaired ROP compared to impaired ROD and CHR. Subgroups in ROP and ROD showed specific symptom- and functioning-patterns. rsFC showed superior accuracy compared to sMRI in differentiating transdiagnostic subgroups from HC (BACimpaired = 58.5%; BACspared = 61.7%, both:p < 0.01). Cognitive findings were validated in the PRONIA replication sample (N = 409). Individual cognitive subgroups in ROP, ROD and CHR are more informative than transdiagnostic subgroups as they map onto individual cognitive impairment and specific functioning- and symptom-patterns which show limited overlap in sMRI and rsFC.

Clinical trial registry name

German Clinical Trials Register (DRKS). Clinical trial registry URL:https://www.drks.de/drks_web/. Clinical trial registry number: DRKS00005042.