Orbitofrontal Thickness and Network Associations as Transdiagnostic Signature of Amotivation Along the Bipolar-Schizophrenia Spectrum.
Overview
13 affiliations
- Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital University of Zurich, 8032 Zurich, Switzerland
- McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, 3801 Montreal, Quebec, Canada
- Division of Adult Psychiatry, Department of Psychiatry, Geneva University Hospitals, 1226 Thônex, Switzerland
- Neuroscience Center Zurich, University of Zurich and Swiss Federal Institute of Technology Zurich, Switzerland
- Department of Psychology, University of Bath, BA2 7AY Bath, United Kingdom
- Clinical Translational Neuroscience Laboratory, Department of Psychiatry and Human Behavior, University of California Irvine, 92697 Irvine, CA, United States
- Center for the Neurobiology of Learning and Memory, University of California Irvine, 92697 Irvine, CA, United States
- Department of Psychiatry and Behavioral Health, The Ohio State University, Columbus, OH 43210, United States
- Institute for Neuroscience and Medicine (INM-7), Forschungszentrum Jülich, 52425 Jülich, Germany
- Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany
- Max Planck School of Cognition, 04103 Leipzig, Germany
- Institute of Systems Neuroscience, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany
- Centre for Sleep & Cognition, Centre for Translational MR Research, Department of Electrical & Computer Engineering, Department of Medicine, National University of Singapore, 117549 Singapore, Singapore
Abstract
Background and Hypothesis: Negative symptoms of schizophrenia (SCZ), particularly amotivation, are prominent across both SCZ and bipolar disorder (BD). While orbitofrontal cortex (OFC) alterations have been implicated in the development of negative symptoms, their contributions across disorders remain to be established. Here, we examined how OFC thickness and network associations relate to amotivation compared to diminished expression across the BD-SCZ spectrum.
Study Design: We included 50 individuals with SCZ, 49 with BD, and 122 controls. We assessed amotivation and diminished expression and estimated thickness in the medial and lateral OFC as regions of interest as well as 64 other cortical regions.
Study Results: Across BD and SCZ, reduced right lateral and bilateral medial OFC thickness were specifically associated with amotivation, but not diminished expression or other clinical factors. We then generated intra-individual OFC structural covariance networks to evaluate how the system-level embedding of the OFC would link to brain-wide cortical maps of negative symptoms. We found that medial OFC covariance networks spatially correlated with the brain-wide cortical alterations of both negative symptom dimensions. Further analyses in independent SCZ data from the ENIGMA consortium (n = 4474) revealed associations with lateral OFC covariance networks. Finally, the brain-wide cortical alterations of amotivation were significantly correlated with normative functional and structural white-matter connectivity profiles of the right medial and left lateral OFC as well as adjacent prefrontal and limbic regions.
Conclusions: Our work identifies OFC alterations as a possible transdiagnostic signature of amotivation and provides insights into network associations underlying the system-wide cortical alterations of negative symptoms across SCZ and BD.
Reproduced under the paper's license (CC BY), from the paper cited above.
Code
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Data
Datasets cited
- openfmri.org/
dataset/ , at openfmri.org; found in “Data availability”ds000030
Data availability
All data used in this study were derived from the UCLA CNP cohort. Data can be downloaded from the publicly available database OpenfMRI (https://
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.
Version 1, 30 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 18 authors, 9 keywords, 12 MeSH terms, 12 funders, 111 references.
Cite
This paper
Franz, M., Kebets, V., Berg, X., Georgiadis, F., Milano, B. A., Burrer, A., Brakowski, J., Kaiser, S., Seifritz, E., Homan, P., Walton, E., van Erp, T. G. M., Turner, J. A., Misic, B., Valk, S. L., Yeo, B. T. T., Bernhardt, B. C., & Kirschner, M. (2026). Orbitofrontal Thickness and Network Associations as Transdiagnostic Signature of Amotivation Along the Bipolar-Schizophrenia Spectrum. Schizophrenia bulletin, 52(2), sbaf078. https://
BibTeX
@article{franz2026orbito
author = {Franz, Marlene and Kebets, Valeria and Berg, Xaver and Georgiadis, Foivos and Milano, Beatrice A and Burrer, Achim and Brakowski, Janis and Kaiser, Stefan and Seifritz, Erich and Homan, Philipp and Walton, Esther and van Erp, Theo G M and Turner, Jessica A and Misic, Bratislav and Valk, Sofie L and Yeo, B T Thomas and Bernhardt, Boris C and Kirschner, Matthias},
title = {{Orbitofrontal Thickness and Network Associations as Transdiagnostic Signature of Amotivation Along the Bipolar-Schizophrenia Spectrum}},
journal = {Schizophrenia bulletin},
year = {2026},
month = mar,
volume = {52},
number = {2},
pages = {sbaf078},
publisher = {Oxford University Press},
issn = {1787-9965},
doi = {10.1093/
url = {https://
pmid = {40579371},
pmcid = {PMC12996912}
}
RIS
TY - JOUR
AU - Franz, Marlene
AU - Kebets, Valeria
AU - Berg, Xaver
AU - Georgiadis, Foivos
AU - Milano, Beatrice A
AU - Burrer, Achim
AU - Brakowski, Janis
AU - Kaiser, Stefan
AU - Seifritz, Erich
AU - Homan, Philipp
AU - Walton, Esther
AU - van Erp, Theo G M
AU - Turner, Jessica A
AU - Misic, Bratislav
AU - Valk, Sofie L
AU - Yeo, B T Thomas
AU - Bernhardt, Boris C
AU - Kirschner, Matthias
TI - Orbitofrontal Thickness and Network Associations as Transdiagnostic Signature of Amotivation Along the Bipolar-Schizophrenia Spectrum
T2 - Schizophrenia bulletin
J2 - Schizophr Bull
PY - 2026
DA - 2026/
VL - 52
IS - 2
SP - sbaf078
SN - 1787-9965
PB - Oxford University Press
DO - 10.1093/
UR - https://
LA - en
ER -
CSL-JSON
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