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Disrupted hierarchical functional brain organization in affective and psychotic disorders: insights from functional brain gradients.

Overview

Authors: Hannah Hacker1, Linnea Hoheisel1,2, Madalina-Octavia Buciuman3, Annkathrin Böke1, Theresa Lichtenstein1, Marlene Rosen1, Shalaila S. Haas4, Anne Ruef3, Dominic B. Dwyer3,5, Paolo Brambilla6,7, Carolina Bonivento8, Rachel Upthegrove9,10, Stephen J. Wood10,11,12, Stefan Borgwardt13, Eva Meisenzahl14, Stephan Ruhrmann1, Raimo K. R. Salokangas15, Alessandro Bertolino16, Rebekka Lencer13,17, Udo Dannlowski17,18,19,20, Nikolaos Koutsouleris3,21,22, Lana Kambeitz-Ilankovic1,23, Joseph Kambeitz1
ORCID iDs: Hannah Hacker, Shalaila S. Haas, Dominic B. Dwyer, Paolo Brambilla, Carolina Bonivento, Stephen J. Wood, Stefan Borgwardt, Stephan Ruhrmann, Rebekka Lencer, Udo Dannlowski, Nikolaos Koutsouleris, Lana Kambeitz-Ilankovic, Joseph Kambeitz
23 affiliations
  1. Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital of Cologne, University of Cologne,Cologne, Germany
  2. Institute of Neuroscience and Medicine (INM-3), Forschungszentrum Jülich,Jülich, Germany
  3. Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University,München, Germany
  4. Department of Psychiatry, Icahn School of Medicine at Mount Sinai,New York, NY USA
  5. Orygen,Melbourne, Australia
  6. Department of Neurosciences and Mental Health, IRCCS Ca’ Granda Ospedale Maggiore Policlinico,Milan, Italy
  7. Department of Pathophysiology and Transplantation, University of Milan,Milano, Italy
  8. Scientific Institute, IRCCS E. Medea, Pasian di Prato,Udine, Italy
  9. Department of Psychiatry, University of Oxford,Oxford, UK
  10. Institute for Mental Health, University of Birmingham,Birmingham, UK
  11. Centre for Mental Health and Brain Sciences, Swinburne University of Technology,Hawthorn, VIC Australia
  12. Centre for Youth Mental Health, University of Melbourne,Parkville, Australia
  13. Department of Psychiatry and Psychotherapy, University of Luebeck,Lübeck, Germany
  14. Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine-University,Düsseldorf, Germany
  15. Department of Psychiatry, University of Turku,Turku, Finland
  16. Department of Translational Biomedicine and Neuroscience University of Bari Aldo Moro,Bari, Italy
  17. Institute for Translational Psychiatry, University of Münster,Münster, Germany
  18. Department of Psychiatry, Medical School and University Medical Center OWL, Protestant Hospital of the Bethel Foundation, Bielefeld University,Bielefeld, Germany
  19. German Center for Mental Health (DZPG), Site Jena Magdeburg Halle,Jena, Germany
  20. Center for Intervention and Research on Adaptive and Maladaptive Brain Circuits Underlying Mental Health (C-I-R-C), Site Jena Magdeburg Halle, Jena, Germany
  21. Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King´s College London,London, UK
  22. Max Planck Institute for Psychiatry,München, Germany
  23. Faculty of Psychology and Educational Sciences, Department of Psychology, Ludwig-Maximilian University,München, Germany
Institutions: University of Cologne (Germany); Forschungszentrum Jülich (Germany); Ludwig-Maximilians-Universität München (Germany); Icahn School of Medicine at Mount Sinai (United States); Orygen (Australia); Department of Neurosciences and Mental Health, IRCCS Ca’ Granda Ospedale Maggiore Policlinico,Milan, Italy; University of Milan (Italy); IRCCS Eugenio Medea (Italy); University of Oxford (United Kingdom); University of Birmingham (United Kingdom); Swinburne University of Technology (Australia); The University of Melbourne (Australia); University of Lübeck (Germany); Heinrich Heine University Düsseldorf (Germany); University of Turku (Finland); University of Bari Aldo Moro (Italy); University of Münster (Germany); Bielefeld University (Germany); Deutsches Zentrum für Psychische Gesundheit (Germany); King's College London (United Kingdom); Max Planck Institute of Psychiatry (Germany)
Journal: Translational psychiatry, volume 16, issue 1, article 384
Dates: received 1 December 2025; accepted 16 June 2026; published online 29 July 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s41398-026-04206-z · PMID 42527394 · PMCID PMC13421452 · OpenAlex W7171713798
Open access: gold, a free copy (OpenAlex)
Status: code on request
Categories: human (organism), depression (population), schizophrenia / psychosis (population), clinical / translational (subfield)
Methods: Statistics, Preprocessing, Connectivity, fMRI & imaging
Keywords: Depression, Schizophrenia
MeSH: Brain*, Connectome*, Mood Disorders*, Nerve Net*, Psychotic Disorders*, Adult, Case-Control Studies, Female, Humans, Magnetic Resonance Imaging, Male, Young Adult (* major topic)
Topic: Functional Brain Connectivity Studies (Cognitive Neuroscience, Neuroscience), according to OpenAlex
Funding: European Union (602152); Universität zu Köln (University of Cologne) (370/2020); National Institute of Mental Health (T32MH122394); DH | NIHR | Health Services Research Programme (NIHR Health Services Research Programme); Deutsche Forschungsgemeinschaft (DFG) (FOR2107 DA1151/5-1, DA1151/5-2, DA1151/9-1, DA1151/10-1, DA1151/11-1, 521379614); Interdisziplinäres Zentrum für Klinische Forschung, Universitätsklinikum Würzburg; Interdisciplinary Center for Clinical Research (IZKF) of the medical faculty of Münster grant Dan3/016/26
Citations: not cited yet (Europe PMC); 70 references in the paper

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.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

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Reproduced under the paper's license (CC BY), from the paper cited above.

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Versions

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Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 23 authors, 2 keywords, 12 MeSH terms, 7 funders, 69 references.

Cite

This paper

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., . . . Kambeitz, J. (2026). Disrupted hierarchical functional brain organization in affective and psychotic disorders: insights from functional brain gradients. Translational psychiatry, 16(1), 384. https://doi.org/10.1038/s41398-026-04206-z

BibTeX

@article{hacker2026disrupted,
author = {Hacker, Hannah and Hoheisel, Linnea and Buciuman, Madalina-Octavia and Böke, Annkathrin and Lichtenstein, Theresa and Rosen, Marlene and Haas, Shalaila S. and Ruef, Anne and Dwyer, Dominic B. and Brambilla, Paolo and Bonivento, Carolina and Upthegrove, Rachel and Wood, Stephen J. and Borgwardt, Stefan and Meisenzahl, Eva and Ruhrmann, Stephan and Salokangas, Raimo K. R. and Bertolino, Alessandro and Lencer, Rebekka and Dannlowski, Udo and Koutsouleris, Nikolaos and Kambeitz-Ilankovic, Lana and Kambeitz, Joseph},
title = {{Disrupted hierarchical functional brain organization in affective and psychotic disorders: insights from functional brain gradients}},
journal = {Translational psychiatry},
year = {2026},
month = jul,
volume = {16},
number = {1},
pages = {384},
publisher = {Nature Publishing Group},
issn = {2158-3188},
doi = {10.1038/s41398-026-04206-z},
url = {https://doi.org/10.1038/s41398-026-04206-z},
pmid = {42527394},
pmcid = {PMC13421452}
}

RIS

TY - JOUR
AU - Hacker, Hannah
AU - Hoheisel, Linnea
AU - Buciuman, Madalina-Octavia
AU - Böke, Annkathrin
AU - Lichtenstein, Theresa
AU - Rosen, Marlene
AU - Haas, Shalaila S.
AU - Ruef, Anne
AU - Dwyer, Dominic B.
AU - Brambilla, Paolo
AU - Bonivento, Carolina
AU - Upthegrove, Rachel
AU - Wood, Stephen J.
AU - Borgwardt, Stefan
AU - Meisenzahl, Eva
AU - Ruhrmann, Stephan
AU - Salokangas, Raimo K. R.
AU - Bertolino, Alessandro
AU - Lencer, Rebekka
AU - Dannlowski, Udo
AU - Koutsouleris, Nikolaos
AU - Kambeitz-Ilankovic, Lana
AU - Kambeitz, Joseph
TI - Disrupted hierarchical functional brain organization in affective and psychotic disorders: insights from functional brain gradients
T2 - Translational psychiatry
J2 - Transl Psychiatry
PY - 2026
DA - 2026/07/29
VL - 16
IS - 1
SP - 384
SN - 2158-3188
PB - Nature Publishing Group
DO - 10.1038/s41398-026-04206-z
UR - https://doi.org/10.1038/s41398-026-04206-z
LA - en
ER -

CSL-JSON

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