Transdiagnostic subgroups of cognitive impairment in early affective and psychotic illness
Julian Wenzel, Luzie Badde, Shalaila S. Haas, Carolina Bonivento, Tamsyn E. Van Rheenen, Linda A. Antonucci, Anne Ruef, Nora Penzel, Marlene Rosen, Theresa Lichtenstein, Paris Alexandros Lalousis, Marco Paolini, Alexandra Stainton, Udo Dannlowski, Georg Romer, Paolo Brambilla, Stephen J. Wood, Rachel Upthegrove, Stefan Borgwardt, Eva Meisenzahl, Raimo K. R. Salokangas, Christos Pantelis, Rebekka Lencer, Alessandro Bertolino, Joseph Kambeitz, Nikolaos Koutsouleris, Dominic Dwyer, Lana Kambeitz‐Ilankovic, Mark Sen Dong, Anne Erkens, Eva Gussmann, Shalaila S. Haas, Alkomiet Hasan, Claudius Hoff, Ifrah Khanyaree, Aylin Melo, Susanna Muckenhuber-Sternbauer, Janis Köhler, Ömer Öztürk, David Popovic, Adrian Rangnick, Sebastian von Saldern, Rachele Sanfelici, Moritz Spangemacher, Ana Tupac, María Fernanda Urquijo, Johanna Weiske, Antonia Wosgien, Stephan Ruhrmann, Linda T. Betz, Karsten Blume, Mauro Seves, Nathalie Kaiser, Tanja Pilgram, Thorsten Lichtenstein, Christiane Woopen, André Schmidt, Anita Riecher‐Rössler, Christina Andreou, Laura Egloff, Fabienne Harrisberger, Claudia Lenz, Letizia Leanza, Amatya Mackintosh, Renata Smieskova, Erich Studerus, Anna Walter, Sonja Widmayer, Katharine Chisholm, Chris Day, Siân Lowri Griffiths, Mariam Iqbal, Mirabel Pelton, Pavan Mallikarjun, Ashleigh Lin, Alexander Denissoff, Anu Ellilä, Tiina From, Markus Heinimaa, Tuula Ilonen, Päivi Jalo, Heikki Laurikainen, Maarit Lehtinen, Antti Luutonen, Akseli Mäkela, Janina Paju, Henri Pesonen, Reetta-Liina Armio, Elina Sormunen, Anna Toivonen, Otto Turtonen, Jarmo Hietala, Mirka Kolkka, Sinikka Luutonen, Maija Walta, Lauri Tuominen, Ana Beatriz Solana, Manuela Abraham, Nicolas Hehn, Timo Schirmer
Abstract
Abstract 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 ( N ROP = 79, N ROD = 30, N CHR = 37) showing cognitive impairment in executive functioning, working memory, processing speed and verbal learning (all p < 0.001). A spared subgroup ( N ROP = 61, N ROD = 100, N CHR = 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 (BAC impaired = 58.5%; BAC spared = 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.