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
Franz et al. (Thu,) studied this question.