Altered functional dynamics gradient in schizophrenia with cigarette smoking

Schizophrenia is associated with a high prevalence of cigarette smoking. Neural dynamics are spatially structured and shaped by both microscale molecular and macroscale functional architectures, which are disturbed in the diseased brain. The neural mechanism underlying the schizophrenia-nicotine dependence comorbidity remains unknown. In this study, we aimed to test whether there is an interaction between schizophrenia and smoking in brain neural dynamics, and how the main effect of the 2 factors related to the molecular architecture. Functional magnetic resonance imaging data were obtained from 4 groups: schizophrenia and healthy controls with/without smoking. We identified 2 dynamics gradients combined with over 5,000 statistical features of the brain region's time series. The interaction effect was found in the high-order functional network, and the main effect of schizophrenia was in the bilateral orbitofrontal cortices. Moreover, the disease- and smoking-related alteration in brain pattern was associated with spatial distribution of serotonin, cannabinoid, and glutamate. Collectively, these findings supported the self-medication hypothesis in schizophrenia-nicotine dependence with a neural intrinsic dynamics perspective.