Transdiagnostic subgroups of cognitive impairment in early affective and psychotic illness

Julian Wenzel; Luzie Badde; Shalaila 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 B. Dwyer; Lana Kambeitz-Ilankovic; Mark Sen Dong; Anne Erkens; Eva Gussmann; Shalaila Haas; Alkomiet Hasan; Claudius Hoff; Ifrah Khanyaree; Aylin Melo; Susanna Muckenhuber-Sternbauer; Janis Kohler; Omer Faruk Ozturk; David Popovic; Adrian Rangnick; Sebastian von Saldern; Rachele Sanfelici; Moritz Spangemacher; Ana Tupac; Maria Fernanda Urquijo; Johanna Weiske; Antonia Wosgien; Stephan Ruhrmann; Linda 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; Sian Lowri Griffiths; Mariam Iqbal; Mirabel Pelton; Pavan Mallikarjun; Ashleigh Lin; Alexander Denissoff; Anu Ellila; Tiina From; Markus Heinimaa; Tuula Ilonen; Paivi Jalo; Heikki Laurikainen; Maarit Lehtinen; Antti Luutonen; Akseli Makela; Janina Paju; Henri Pesonen; Reetta Liina Armio (Säilä); 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; Carlo Altamura; Marika Belleri; Francesca Bottinelli; Adele Ferro; Marta Re; Emiliano Monzani; Mauro Percudani; Maurizio Sberna; Armando D’Agostino; Lorenzo Del Fabro; Giampaolo Perna; Maria Nobile; Alessandra Alciati; Matteo Balestrieri; Giuseppe Cabras; Franco Fabbro; Marco Garzitto; Sara Piccin; Giuseppe Blasi; Giulio Pergola; Grazia Caforio; Leonardo Facio; Tiziana Quarto; Barbara Gelao; Raffaella Romano; Ileana Andriola; Andrea Falsetti; Marina Barone; Roberta Passatiore; Marina Sangiuliano; Marian Surman; Olga Bienek; Frauke Schultze-Lutter; Christian Schmidt-Kraepelin; Susanne Neufang; Alexandra Korda; Henrik Rohner

doi:10.1038/s41386-023-01729-7

Transdiagnostic subgroups of cognitive impairment in early affective and psychotic illness

Julian Wenzel^*, Luzie Badde, Shalaila 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 MeisenzahlRaimo K.R. Salokangas, Christos Pantelis, Rebekka Lencer, Alessandro Bertolino, Joseph Kambeitz, Nikolaos Koutsouleris, Dominic B. Dwyer, Lana Kambeitz-Ilankovic, Mark Sen Dong, Anne Erkens, Eva Gussmann, Shalaila Haas, Alkomiet Hasan, Claudius Hoff, Ifrah Khanyaree, Aylin Melo, Susanna Muckenhuber-Sternbauer, Janis Kohler, Omer Faruk Ozturk, David Popovic, Adrian Rangnick, Sebastian von Saldern, Rachele Sanfelici, Moritz Spangemacher, Ana Tupac, Maria Fernanda Urquijo, Johanna Weiske, Antonia Wosgien, Stephan Ruhrmann, Linda 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, Sian Lowri Griffiths, Mariam Iqbal, Mirabel Pelton, Pavan Mallikarjun, Ashleigh Lin, Alexander Denissoff, Anu Ellila, Tiina From, Markus Heinimaa, Tuula Ilonen, Paivi Jalo, Heikki Laurikainen, Maarit Lehtinen, Antti Luutonen, Akseli Makela, Janina Paju, Henri Pesonen, Reetta Liina Armio (Säilä), 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, Carlo Altamura, Marika Belleri, Francesca Bottinelli, Adele Ferro, Marta Re, Emiliano Monzani, Mauro Percudani, Maurizio Sberna, Armando D’Agostino, Lorenzo Del Fabro, Giampaolo Perna, Maria Nobile, Alessandra Alciati, Matteo Balestrieri, Giuseppe Cabras, Franco Fabbro, Marco Garzitto, Sara Piccin, Giuseppe Blasi, Giulio Pergola, Grazia Caforio, Leonardo Facio, Tiziana Quarto, Barbara Gelao, Raffaella Romano, Ileana Andriola, Andrea Falsetti, Marina Barone, Roberta Passatiore, Marina Sangiuliano, Marian Surman, Olga Bienek, Frauke Schultze-Lutter, Christian Schmidt-Kraepelin, Susanne Neufang, Alexandra Korda, Henrik Rohner

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

5 Citations (Scopus)

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.

Original language	English
Pages (from-to)	573-583
Number of pages	11
Journal	Neuropsychopharmacology
Volume	49
Issue number	3
DOIs	https://doi.org/10.1038/s41386-023-01729-7
Publication status	Published - Feb 2024

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10.1038/s41386-023-01729-7

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Wenzel, J., Badde, L., Haas, S., Bonivento, C., Van Rheenen, T. E., Antonucci, L. A., Ruef, A., Penzel, N., Rosen, M., Lichtenstein, T., Lalousis, P. A., Paolini, M., Stainton, A., Dannlowski, U., Romer, G., Brambilla, P., Wood, S. J., Upthegrove, R., Borgwardt, S., ... Rohner, H. (2024). Transdiagnostic subgroups of cognitive impairment in early affective and psychotic illness. Neuropsychopharmacology, 49(3), 573-583. https://doi.org/10.1038/s41386-023-01729-7

@article{2b9ed012761446988fffdbfc52410667,

title = "Transdiagnostic subgroups of cognitive impairment in early affective and psychotic illness",

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 (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.",

author = "Julian Wenzel and Luzie Badde and Shalaila Haas and Carolina Bonivento and {Van Rheenen}, {Tamsyn E.} and Antonucci, {Linda A.} and Anne Ruef and Nora Penzel and Marlene Rosen and Theresa Lichtenstein and Lalousis, {Paris Alexandros} and Marco Paolini and Alexandra Stainton and Udo Dannlowski and Georg Romer and Paolo Brambilla and Wood, {Stephen J.} and Rachel Upthegrove and Stefan Borgwardt and Eva Meisenzahl and Salokangas, {Raimo K.R.} and Christos Pantelis and Rebekka Lencer and Alessandro Bertolino and Joseph Kambeitz and Nikolaos Koutsouleris and Dwyer, {Dominic B.} and Lana Kambeitz-Ilankovic and Dong, {Mark Sen} and Anne Erkens and Eva Gussmann and Shalaila Haas and Alkomiet Hasan and Claudius Hoff and Ifrah Khanyaree and Aylin Melo and Susanna Muckenhuber-Sternbauer and Janis Kohler and Ozturk, {Omer Faruk} and David Popovic and Adrian Rangnick and {von Saldern}, Sebastian and Rachele Sanfelici and Moritz Spangemacher and Ana Tupac and Urquijo, {Maria Fernanda} and Johanna Weiske and Antonia Wosgien and Stephan Ruhrmann and Linda Betz and Karsten Blume and Mauro Seves and Nathalie Kaiser and Tanja Pilgram and Thorsten Lichtenstein and Christiane Woopen and Andr{\'e} Schmidt and Anita Riecher-R{\"o}ssler and Christina Andreou and Laura Egloff and Fabienne Harrisberger and Claudia Lenz and Letizia Leanza and Amatya Mackintosh and Renata Smieskova and Erich Studerus and Anna Walter and Sonja Widmayer and Katharine Chisholm and Chris Day and Griffiths, {Sian Lowri} and Mariam Iqbal and Mirabel Pelton and Pavan Mallikarjun and Ashleigh Lin and Alexander Denissoff and Anu Ellila and Tiina From and Markus Heinimaa and Tuula Ilonen and Paivi Jalo and Heikki Laurikainen and Maarit Lehtinen and Antti Luutonen and Akseli Makela and Janina Paju and Henri Pesonen and {Armio (S{\"a}il{\"a})}, {Reetta Liina} and Elina Sormunen and Anna Toivonen and Otto Turtonen and Jarmo Hietala and Mirka Kolkka and Sinikka Luutonen and Maija Walta and Lauri Tuominen and Solana, {Ana Beatriz} and Manuela Abraham and Nicolas Hehn and Timo Schirmer and Carlo Altamura and Marika Belleri and Francesca Bottinelli and Adele Ferro and Marta Re and Emiliano Monzani and Mauro Percudani and Maurizio Sberna and Armando D{\textquoteright}Agostino and {Del Fabro}, Lorenzo and Giampaolo Perna and Maria Nobile and Alessandra Alciati and Matteo Balestrieri and Giuseppe Cabras and Franco Fabbro and Marco Garzitto and Sara Piccin and Giuseppe Blasi and Giulio Pergola and Grazia Caforio and Leonardo Facio and Tiziana Quarto and Barbara Gelao and Raffaella Romano and Ileana Andriola and Andrea Falsetti and Marina Barone and Roberta Passatiore and Marina Sangiuliano and Marian Surman and Olga Bienek and Frauke Schultze-Lutter and Christian Schmidt-Kraepelin and Susanne Neufang and Alexandra Korda and Henrik Rohner",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2024",

month = feb,

doi = "10.1038/s41386-023-01729-7",

language = "English",

volume = "49",

pages = "573--583",

journal = "Neuropsychopharmacology",

issn = "0893-133X",

publisher = "Springer Nature [academic journals on nature.com]",

number = "3",

}

Wenzel, J, Badde, L, Haas, S, Bonivento, C, Van Rheenen, TE, Antonucci, LA, Ruef, A, Penzel, N, Rosen, M, Lichtenstein, T, Lalousis, PA, Paolini, M, Stainton, A, Dannlowski, U, Romer, G, Brambilla, P, Wood, SJ, Upthegrove, R, Borgwardt, S, Meisenzahl, E, Salokangas, RKR, Pantelis, C, Lencer, R, Bertolino, A, Kambeitz, J, Koutsouleris, N, Dwyer, DB, Kambeitz-Ilankovic, L, Dong, MS, Erkens, A, Gussmann, E, Haas, S, Hasan, A, Hoff, C, Khanyaree, I, Melo, A, Muckenhuber-Sternbauer, S, Kohler, J, Ozturk, OF, Popovic, D, Rangnick, A, von Saldern, S, Sanfelici, R, Spangemacher, M, Tupac, A, Urquijo, MF, Weiske, J, Wosgien, A, Ruhrmann, S, Betz, L, Blume, K, Seves, M, Kaiser, N, Pilgram, T, Lichtenstein, T, Woopen, C, Schmidt, A, Riecher-Rössler, A, Andreou, C, Egloff, L, Harrisberger, F, Lenz, C, Leanza, L, Mackintosh, A, Smieskova, R, Studerus, E, Walter, A, Widmayer, S, Chisholm, K, Day, C, Griffiths, SL, Iqbal, M, Pelton, M, Mallikarjun, P, Lin, A, Denissoff, A, Ellila, A, From, T, Heinimaa, M, Ilonen, T, Jalo, P, Laurikainen, H, Lehtinen, M, Luutonen, A, Makela, A, Paju, J, Pesonen, H, Armio (Säilä), RL, Sormunen, E, Toivonen, A, Turtonen, O, Hietala, J, Kolkka, M, Luutonen, S, Walta, M, Tuominen, L, Solana, AB, Abraham, M, Hehn, N, Schirmer, T, Altamura, C, Belleri, M, Bottinelli, F, Ferro, A, Re, M, Monzani, E, Percudani, M, Sberna, M, D’Agostino, A, Del Fabro, L, Perna, G, Nobile, M, Alciati, A, Balestrieri, M, Cabras, G, Fabbro, F, Garzitto, M, Piccin, S, Blasi, G, Pergola, G, Caforio, G, Facio, L, Quarto, T, Gelao, B, Romano, R, Andriola, I, Falsetti, A, Barone, M, Passatiore, R, Sangiuliano, M, Surman, M, Bienek, O, Schultze-Lutter, F, Schmidt-Kraepelin, C, Neufang, S, Korda, A & Rohner, H 2024, 'Transdiagnostic subgroups of cognitive impairment in early affective and psychotic illness', Neuropsychopharmacology, vol. 49, no. 3, pp. 573-583. https://doi.org/10.1038/s41386-023-01729-7

TY - JOUR

T1 - Transdiagnostic subgroups of cognitive impairment in early affective and psychotic illness

AU - Wenzel, Julian

AU - Badde, Luzie

AU - Haas, Shalaila

AU - Bonivento, Carolina

AU - Van Rheenen, Tamsyn E.

AU - Antonucci, Linda A.

AU - Ruef, Anne

AU - Penzel, Nora

AU - Rosen, Marlene

AU - Lichtenstein, Theresa

AU - Lalousis, Paris Alexandros

AU - Paolini, Marco

AU - Stainton, Alexandra

AU - Dannlowski, Udo

AU - Romer, Georg

AU - Brambilla, Paolo

AU - Wood, Stephen J.

AU - Upthegrove, Rachel

AU - Borgwardt, Stefan

AU - Meisenzahl, Eva

AU - Salokangas, Raimo K.R.

AU - Pantelis, Christos

AU - Lencer, Rebekka

AU - Bertolino, Alessandro

AU - Kambeitz, Joseph

AU - Koutsouleris, Nikolaos

AU - Dwyer, Dominic B.

AU - Kambeitz-Ilankovic, Lana

AU - Dong, Mark Sen

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 - Ozturk, Omer Faruk

AU - Popovic, David

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 - Ruhrmann, Stephan

AU - Betz, Linda

AU - Blume, Karsten

AU - Seves, Mauro

AU - Kaiser, Nathalie

AU - Pilgram, Tanja

AU - Lichtenstein, Thorsten

AU - Woopen, Christiane

AU - Schmidt, André

AU - Riecher-Rössler, Anita

AU - Andreou, Christina

AU - Egloff, Laura

AU - Harrisberger, Fabienne

AU - Lenz, Claudia

AU - Leanza, Letizia

AU - Mackintosh, Amatya

AU - Smieskova, Renata

AU - Studerus, Erich

AU - Walter, Anna

AU - Widmayer, Sonja

AU - Chisholm, Katharine

AU - Day, Chris

AU - Griffiths, Sian Lowri

AU - Iqbal, Mariam

AU - Pelton, Mirabel

AU - Mallikarjun, Pavan

AU - Lin, Ashleigh

AU - Denissoff, Alexander

AU - Ellila, Anu

AU - From, Tiina

AU - Heinimaa, Markus

AU - Ilonen, Tuula

AU - Jalo, Paivi

AU - Laurikainen, Heikki

AU - Lehtinen, Maarit

AU - Luutonen, Antti

AU - Makela, Akseli

AU - Paju, Janina

AU - Pesonen, Henri

AU - Armio (Säilä), Reetta Liina

AU - Sormunen, Elina

AU - Toivonen, Anna

AU - Turtonen, Otto

AU - Hietala, Jarmo

AU - Kolkka, Mirka

AU - Luutonen, Sinikka

AU - Walta, Maija

AU - Tuominen, Lauri

AU - Solana, Ana Beatriz

AU - Abraham, Manuela

AU - Hehn, Nicolas

AU - Schirmer, Timo

AU - Altamura, Carlo

AU - Belleri, Marika

AU - Bottinelli, Francesca

AU - Ferro, Adele

AU - Re, Marta

AU - Monzani, Emiliano

AU - Percudani, Mauro

AU - Sberna, Maurizio

AU - D’Agostino, Armando

AU - Del Fabro, Lorenzo

AU - Perna, Giampaolo

AU - Nobile, Maria

AU - Alciati, Alessandra

AU - Balestrieri, Matteo

AU - Cabras, Giuseppe

AU - Fabbro, Franco

AU - Garzitto, Marco

AU - Piccin, Sara

AU - Blasi, Giuseppe

AU - Pergola, Giulio

AU - Caforio, Grazia

AU - Facio, Leonardo

AU - Quarto, Tiziana

AU - Gelao, Barbara

AU - Romano, Raffaella

AU - Andriola, Ileana

AU - Falsetti, Andrea

AU - Barone, Marina

AU - Passatiore, Roberta

AU - Sangiuliano, Marina

AU - Surman, Marian

AU - Bienek, Olga

AU - Schultze-Lutter, Frauke

AU - Schmidt-Kraepelin, Christian

AU - Neufang, Susanne

AU - Korda, Alexandra

AU - Rohner, Henrik

PY - 2024/2

Y1 - 2024/2

N2 - 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 (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.

AB - 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 (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.

UR - http://www.scopus.com/inward/record.url?scp=85171837194&partnerID=8YFLogxK

U2 - 10.1038/s41386-023-01729-7

DO - 10.1038/s41386-023-01729-7

M3 - Article

C2 - 37737273

AN - SCOPUS:85171837194

SN - 0893-133X

VL - 49

SP - 573

EP - 583

JO - Neuropsychopharmacology

JF - Neuropsychopharmacology

IS - 3

ER -

Transdiagnostic subgroups of cognitive impairment in early affective and psychotic illness

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