Disconnectivity between the raphe nucleus and subcortical dopamine-related regions contributes altered salience...

Numerous studies strongly have suggested the significant role of serotonin in the pathomechanism of schizophrenia. However, few studies have directly explored the altered serotonin function in schizophrenia. In the current study, we explored the altered serotonin function in first-episode treatment-naive patients with schizophrenia with resting-state functional magnetic resonance imaging. A total 42 first-episode treatment-naive patients with schizophrenia and carefully matched healthy controls are included in the study. Considering that the raphe nucleus providing a substantial proportion of the serotonin innervation to the forebrain, the raphe nucleus was chosen as the seed to construct voxel-based functional connectivity (FC) maps. In the results, subcortical dopamine-related regions presented decreased FC with the raphe nucleus, such as the bilateral striatum, pallidum, and thalamus, in patients with schizophrenia. Decreased FC in these regions was significantly correlated with the total negative scores in PANSS. Furthermore, these regions presented with decreased FC connection to salience network. Our results presented that the raphe nucleus played an important role in the dysfunction of subcortical DA-related regions, and contributed to the altered salience network in schizophrenia. Our study emphasized the importance of the raphe nucleus in the pathophysiology of schizophrenia.