Distinct multimodal biological and functional profiles of symptom-based subgroups in recent-onset psychosis.

Autor:	Koutsouleris N; Ludwig-Maximilians-University., Buciuman MO; Ludwig-Maximilians-University., Vetter CS; Ludwig-Maximilians-University., Weyer CFC; Ludwig-Maximilians-University., Zhutovsky P; Amstedam Medical Center., Perdomo ST; Ludwig-Maximilians-University., Khuntia A; Amsterdam UMC, Vrije Universiteit/GGZ inGeest., Milaneschi Y; Amsterdam UMC, Vrije Universiteit/GGZ inGeest., Popovic D; Ludwig-Maximilians-University., Ruef A; LMU., Dwyer D; Aston University., Chisholm K; Aston University., Kambeitz L; University of Cologne, Faculty of Medicine and University Hospital., Antonucci L; Faculty of Medicine and University Hospital, University of Cologne, Cologne., Ruhrmann S; Faculty of Medicine and University Hospital, University of Cologne, Cologne., Kambeitz J; Faculty of Medicine and University Hospital, University of Cologne, Cologne., Riecher-Rössler A; University of Basel., Upthegrove R; University of Birmingham., Salokangas R; University of Turku., Hietala J; University of Turku., Pantelis C; University of Melbourne., Lencer R; University of Melbourne., Meisenzahl E; University of Melbourne., Wood S; University of Melbourne., Brambilla P; University of Milan., Borgwardt S; University of Lübeck., Bertolino A; Group of Psychiatric Neuroscience, Department of Basic Medical Science, Neuroscience and Sense Organs, Aldo Moro University, Bari., Falkai P; University Hospital LMU.
Jazyk:	angličtina
Zdroj:	Research square [Res Sq] 2024 Mar 13. Date of Electronic Publication: 2024 Mar 13.
DOI:	10.21203/rs.3.rs-3949072/v1
Abstrakt:	Symptom heterogeneity characterizes psychotic disorders and hinders the delineation of underlying biomarkers. Here, we identify symptom-based subtypes of recent-onset psychosis (ROP) patients from the multi-center PRONIA (Personalized Prognostic Tools for Early Psychosis Management) database and explore their multimodal biological and functional signatures. We clustered N = 328 ROP patients based on their maximum factor scores in an exploratory factor analysis on the Positive and Negative Syndrome Scale items. We assessed inter-subgroup differences and compared to N = 464 healthy control (HC) individuals regarding gray matter volume (GMV), neurocognition, polygenic risk scores, and longitudinal functioning trajectories. Finally, we evaluated factor stability at 9- and 18-month follow-ups. A 4-factor solution optimally explained symptom heterogeneity, showing moderate longitudinal stability. The ROP-MOTCOG ( Motor/Cognition ) subgroup was characterized by GMV reductions within salience, control and default mode networks, predominantly throughout cingulate regions, relative to HC individuals, had the most impaired neurocognition and the highest genetic liability for schizophrenia. ROP-SOCWD ( Social Withdrawal ) patients showed GMV reductions within medial fronto-temporal regions of the control, default mode, and salience networks, and had the lowest social functioning across time points. ROP-POS ( Positive ) evidenced GMV decreases in salience, limbic and frontal regions of the control and default mode networks. The ROP-AFF ( Affective ) subgroup showed GMV reductions in the salience, limbic, and posterior default-mode and control networks, thalamus and cerebellum. GMV reductions in fronto-temporal regions of the salience and control networks were shared across subgroups. Our results highlight the existence of behavioral subgroups with distinct neurobiological and functional profiles in early psychosis, emphasizing the need for refined symptom-based diagnosis and prognosis frameworks. Competing Interests: Conflict of Interest/Financial disclosure Dr Bertolino reports speaker fees from Otsuka, Lundbeck, Angelini and Rovi outside of the submitted work. Dr Hietala reports personal fees from Orion ltd, personal fees from Lundbeck, personal fees from Otsuka and other from Takeda during the conduct of the study. Dr Koutsouleris, Dr Ruhrmann, Dr Riecher-Rossler report grants from European Union over the duration of the study. Dr Meisenzahl and Dr Koutsouleris hold patent US20160192889A1 (‘Adaptive pattern recognition for psychosis risk modelling’). Dr Koutsouleris reports speaker fees from Otsuka, Roche and Angelini outside of the submitted work. Dr Pantelis reports grants from Australian NHMRC during the study, and personal fees from Lundbeck, Australia Pty Ltd outside the submitted work. Dr Upthegrove reports speaker fees from Sunovion, Otsuka and Vitaris outside the submitted work as well as unpaid officership with the British Association for Pharmacology - Honorary General Secretary 2021–2024. She serves as Deputy Editor for The British Journal of Psychiatry. Dr Falkai reports he has received research support/honoraria for lectures or advisory activities from Boehringer-Ingelheim, Janssen, Lundbeck, Otsuka, Recordati and Richter outside the submitted work. Dr Pantelis was supported by an Australian National Health and Medical Research Council (NHMRC) L3 Investigator Grant (1196508) outside the submitted work. Dr Lana Kambeitz-Ilankovic reports receiving a NARSAD Young Investigator Award of the Brain & Behavior Research Foundation No° 28474 (PI: LK-I) outside the submitted work. Dr Milaneschi reports consulting fees from Noema Pharma outside the submitted work. Dr Upthegrove reports support from the UK NIHR Oxford Health Biomedical Research Centre. The views expressed are those of the author and not necessarily those of the NIHR or the Department of Health and Social Care. All other co-authors did not report any other financial disclosures or other conflicts of interests within or outside of the scope of the submitted work.
Databáze:	MEDLINE
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