Journal Article FZJ-2026-01140

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Orbitofrontal Thickness and Network Associations as Transdiagnostic Signature of Amotivation Along the Bipolar-Schizophrenia Spectrum

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2025
Oxford Univ. Press Oxford

Schizophrenia bulletin -, sbaf078 () [10.1093/schbul/sbaf078]

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Abstract: Background and Hypothesis: Negative symptoms of schiz-ophrenia (SCZ), particularly amotivation, are prominentacross both SCZ and bipolar disorder (BD). While orbit-ofrontal cortex (OFC) alterations have been implicated inthe development of negative symptoms, their contributionsacross disorders remain to be established. Here, we exam-ined how OFC thickness and network associations relate toamotivation compared to diminished expression across theBD-SCZ spectrum.Study Design: We included 50 individuals with SCZ, 49with BD, and 122 controls. We assessed amotivation anddiminished expression and estimated thickness in the me-dial and lateral OFC as regions of interest as well as 64other cortical regions.Study Results: Across BD and SCZ, reduced right lateraland bilateral medial OFC thickness were specifically asso-ciated with amotivation, but not diminished expression orother clinical factors. We then generated intra-individualOFC structural covariance networks to evaluate how thesystem-level embedding of the OFC would link to brain-wide cortical maps of negative symptoms. We found thatmedial OFC covariance networks spatially correlatedwith the brain-wide cortical alterations of both negativesymptom dimensions. Further analyses in independentSCZ data from the ENIGMA consortium (n = 4474) re-vealed associations with lateral OFC covariance networks.Finally, the brain-wide cortical alterations of amotivationwere significantly correlated with normative functional andstructural white-matter connectivity profiles of the rightmedial and left lateral OFC as well as adjacent prefrontaland limbic regions.Conclusions: Our work identifies OFC alterations as a pos-sible transdiagnostic signature of amotivation and providesinsights into network associations underlying the system-wide cortical alterations of negative symptoms across SCZand BD

Classification:

Contributing Institute(s):
  1. Gehirn & Verhalten (INM-7)
Research Program(s):
  1. 5251 - Multilevel Brain Organization and Variability (POF4-525) (POF4-525)
  2. 5252 - Brain Dysfunction and Plasticity (POF4-525) (POF4-525)

Database coverage:
Medline ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Current Contents - Social and Behavioral Sciences ; Essential Science Indicators ; IF >= 5 ; JCR ; NationallizenzNationallizenz ; SCOPUS ; Science Citation Index Expanded ; Social Sciences Citation Index ; Web of Science Core Collection
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 Record created 2026-01-27, last modified 2026-01-27



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