Distinct multimodal biological and functional profiles of symptom-based subgroups in recent-onset psychosis
Author:
Koutsouleris Nikolaos1ORCID, Buciuman Madalina-Octavia1, Vetter Clara Sophie1, Weyer Clara Francesca Charlotte1, Zhutovsky Paul2, Perdomo Santiago Tovar1, Khuntia Adyasha, milaneschi yuri3ORCID, Popovic David1ORCID, Ruef Anne4, Dwyer Dominic, Chisholm Katharine5ORCID, Kambeitz Lana6, Antonucci Linda, Ruhrmann StephanORCID, Kambeitz Joseph7ORCID, Riecher-Rössler Anita8ORCID, Upthegrove Rachel9ORCID, Salokangas Raimo10, Hietala Jarmo10ORCID, Pantelis Christos11ORCID, Lencer Rebekka, Meisenzahl Eva, Wood Stephen11, Brambilla Paolo12ORCID, Borgwardt Stefan13ORCID, Bertolino Alessandro14, Falkai Peter15
Affiliation:
1. Ludwig-Maximilians-University 2. Amstedam Medical Center 3. Amsterdam UMC, Vrije Universiteit/GGZ inGeest 4. LMU 5. Aston University 6. University of Cologne, Faculty of Medicine and University Hospital 7. Faculty of Medicine and University Hospital, University of Cologne, Cologne 8. University of Basel 9. University of Birmingham 10. University of Turku 11. University of Melbourne 12. University of Milan 13. University of Lübeck 14. Group of Psychiatric Neuroscience, Department of Basic Medical Science, Neuroscience and Sense Organs, Aldo Moro University, Bari 15. University Hospital LMU
Abstract
Abstract
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.
Publisher
Research Square Platform LLC
Reference90 articles.
1. The new field of ‘precision psychiatry,’;Fernandes BS;BMC Med.,2017 2. K. J. Friston, “Precision psychiatry,” Biological psychiatry: cognitive neuroscience and neuroimaging, vol. 2, no. 8. Elsevier BV, pp. 640–643, Nov-2017. 3. American Psychiatric Association. Diagnostic and statistical manual of mental disoders.. 4. T. Insel et al., “Research domain criteria (RDoC): toward a new classification framework for research on mental disorders,” Am. J. Psychiatry, vol. 167, no. 7, pp. 748–751, Jul. 2010. 5. The Hierarchical Taxonomy of Psychopathology (HiTOP): A dimensional alternative to traditional nosologies;Kotov R;J. Abnorm. Psychol.,2017
|
|