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 B. Dwyer; Lana Kambeitz-Ilankovic; PRONIA Consortium

doi:10.1038/s41386-023-01729-7

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 MeisenzahlRaimo K. R. Salokangas, Christos Pantelis, Rebekka Lencer, Alessandro Bertolino, Joseph Kambeitz, Nikolaos Koutsouleris, Dominic B. Dwyer, Lana Kambeitz-Ilankovic, PRONIA Consortium

^*Corresponding author for this work

Psychology

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

15 Downloads (Pure)

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 (NROP = 79, NROD = 30, NCHR = 37) showing cognitive impairment in executive functioning, working memory, processing speed and verbal learning (all p < 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.

Original language	English
Pages (from-to)	573-583
Number of pages	11
Journal	Neuropsychopharmacology
Volume	49
Issue number	3
Early online date	22 Sept 2023
DOIs	https://doi.org/10.1038/s41386-023-01729-7
Publication status	Published - Feb 2024

Bibliographical note

Funding
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 & Behavior Research Foundation (grant number 28474). RU achieved grants from Medical Research Council, grants from the National Institute for Health Research, and personal fees from Sunovion. TL was supported by the Koeln Fortune Program/Faculty of Medicine, University of Cologne (No 370/2020). CP was supported by a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellowship (1105825), an NHMRC L3 Investigator Grant (1196508), and NHMRC-EU grant (1075379). SSH was supported by NIH National Institute of Mental Health, grant T32MH122394. TEVR was supported by an Al and Val Rosenstrauss Fellowship from the Rebecca L. Cooper Medical Research Foundation. This paper should be linked to a future Research Highlight to be written by Dr. Kathryn Lewandowski. Open Access funding enabled and organized by Projekt DEAL.

Access to Document

10.1038/s41386-023-01729-7Licence: Creative Commons: Attribution (CC BY)

WenzelJ2024Transdiagnostic.pdfFinal published version, 3.05 MBLicence: Creative Commons: Attribution (CC BY)

Cite this

Wenzel, J., Badde, L., Haas, S. 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., ... PRONIA Consortium (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{b35e6a8c3d2a439cafdde8bf0753640a,

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

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 (NROP = 79, NROD = 30, NCHR = 37) showing cognitive impairment in executive functioning, working memory, processing speed and verbal learning (all p < 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.",

author = "Julian Wenzel and Luzie Badde and Haas, {Shalaila S.} 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 {PRONIA Consortium}",

note = "Funding 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 & Behavior Research Foundation (grant number 28474). RU achieved grants from Medical Research Council, grants from the National Institute for Health Research, and personal fees from Sunovion. TL was supported by the Koeln Fortune Program/Faculty of Medicine, University of Cologne (No 370/2020). CP was supported by a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellowship (1105825), an NHMRC L3 Investigator Grant (1196508), and NHMRC-EU grant (1075379). SSH was supported by NIH National Institute of Mental Health, grant T32MH122394. TEVR was supported by an Al and Val Rosenstrauss Fellowship from the Rebecca L. Cooper Medical Research Foundation. This paper should be linked to a future Research Highlight to be written by Dr. Kathryn Lewandowski. Open Access funding enabled and organized by Projekt DEAL.",

year = "2024",

month = feb,

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

language = "English",

volume = "49",

pages = "573--583",

journal = "Neuropsychopharmacology",

issn = "0893-133X",

publisher = "Nature Publishing Group",

number = "3",

}

Wenzel, J, Badde, L, Haas, SS, 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 & PRONIA Consortium 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 S.

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 - PRONIA Consortium

N1 - Funding 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 & Behavior Research Foundation (grant number 28474). RU achieved grants from Medical Research Council, grants from the National Institute for Health Research, and personal fees from Sunovion. TL was supported by the Koeln Fortune Program/Faculty of Medicine, University of Cologne (No 370/2020). CP was supported by a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellowship (1105825), an NHMRC L3 Investigator Grant (1196508), and NHMRC-EU grant (1075379). SSH was supported by NIH National Institute of Mental Health, grant T32MH122394. TEVR was supported by an Al and Val Rosenstrauss Fellowship from the Rebecca L. Cooper Medical Research Foundation. This paper should be linked to a future Research Highlight to be written by Dr. Kathryn Lewandowski. Open Access funding enabled and organized by Projekt DEAL.

PY - 2024/2

Y1 - 2024/2

N2 - 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 (all p < 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.

AB - 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 (all p < 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.

U2 - 10.1038/s41386-023-01729-7

DO - 10.1038/s41386-023-01729-7

M3 - Article

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

Abstract

Bibliographical note

Access to Document

Fingerprint

Cite this