Journal Article

FZJ-2026-04875

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Disrupted hierarchical functional brain organization in affective and psychotic disorders: insights from functional brain gradients

Hacker, H. ; Hoheisel, L. ; Buciuman, M.-O. ; Böke, A. ; Lichtenstein, T. ; Rosen, M. ; Haas, S. S. ; Ruef, A. ; Dwyer, D. B. ; Brambilla, P. ; Bonivento, C. ; Upthegrove, R. ; Wood, S. J. ; Borgwardt, S. ; Meisenzahl, E. ; Ruhrmann, S. ; Salokangas, R. K. R. ; Bertolino, A. ; Lencer, R. ; Dannlowski, U. ; Koutsouleris, N. ; Kambeitz-Ilankovic, L. ; Kambeitz, J. (Corresponding author)

2026
Nature Publishing Group London

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Please use a persistent id in citations: doi:10.1038/s41398-026-04206-z  doi:10.34734/FZJ-2026-04875

Abstract: Individuals with psychosis and depression show widespread alterations in brain resting-state functional connectivity (rs-FC), affecting both sensory and higher-order brain regions. In this study, we investigate disruptions in the hierarchical organization of brain functional networks in individuals with psychotic and affective disorders. We derived functional brain gradients, low dimensional representations of rs-FC that capture cortical hierarchy, in a sample of 1071 (56.3% female) participants, including clinical high-risk for psychosis (CHR-P) individuals, recent-onset psychosis (ROP) patients, recent-onset depression (ROD) patients, and healthy controls (HC). We examined regional alterations, network-level alterations and functional differentiation and their relationship to clinical symptoms. In addition, we linked case-control differences to receptor expression maps to explore underlying neurobiological mechanisms. All clinical groups exhibited alterations in the visual-to-sensorimotor gradient, while only ROP patients showed alterations in the sensory-to-association gradient. CHR-P and ROP individuals exhibited lower values in the ventral attention network. Clinical groups combined showed higher values in the somatomotor network, a reduced gradient range and altered between-network dispersion. ROD patients showed reduced within-network dispersion in the attentional networks and a reduced range. Correlational analysis revealed weak associations of gradient measures with functioning, visual dysfunctions and cognition. Case-control differences showed associations to receptor expression maps, suggesting the involvement of neurotransmitter systems in these disruptions. Our findings reveal transdiagnostic and disease-specific alterations of hierarchical brain organization. These alterations indicate deficits in functional integration across psychiatric diseases, highlighting the role of attentional and sensory networks in disease processes.Subject terms: Depression, Schizophrenia

Note: Wer ist denn der interne Autor??PRONIA is a Collaboration Project funded by the European Union under the 7th Framework Programme under grant agreement n° 602152. RU is supported by the NIHR Oxford Health Biomedical Research Centre, achieved grants from Medical Research Council and grants from the National Institute for Health Research. TL is supported by the Advanced Cologne Clinician Scientist Program (adCCSP) / Faculty of Medicine / University of Cologne and was supported by the Koeln Fortune Program/ Faculty of Medicine, University of Cologne (No 370/2020). CB was funded by the Italian Ministry of Health (Ricerca Corrente 2026). SH was supported by the NIH National Institute of Mental Health grant T32MH122394. UD was funded by the German Research Foundation (DFG, grant FOR2107 DA1151/5-1, DA1151/5-2, DA1151/9-1, DA1151/10-1, DA1151/11-1 to UD; SFB/TRR 393, project grant no 521379614) and the Interdisciplinary Center for Clinical Research (IZKF) of the medical faculty of Münster (grant Dan3/016/26 to UD). Open Access funding enabledand organized by Projekt DEAL.

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Contributing Institute(s):

1. Kognitive Neurowissenschaften (INM-3)

Research Program(s):

1. 5252 - Brain Dysfunction and Plasticity (POF4-525) (POF4-525)

Appears in the scientific report 2026

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