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

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.

Frequency-selective alteration in the resting-state corticostriatal-thalamo-cortical circuit correlates with symptoms severity in first-episode drug-naive patients with schizophrenia.

Schizophrenia is a prototypical disorder of brain connectivity with altered neural activity in regions extending throughout the brain. Regions, including the subcortex and cortex, present activity mainly within a specific frequency band in resting-state. Whether these altered resting-state functional connections also present frequency specificity is unknown. In the present study, empirical mode decomposition, which is a pure data-driven method suitable for nonlinear and nonstationary signals, was used to decompose blood-oxygen-level-dependent (BOLD) signals into different intrinsic frequency bands. Our study included 42 first-episode drug-naive patients with schizophrenia and 38 controls. Significant aberration in functional connectivity was observed only at a higher frequency range (the peak spectral density power was 0.06Hz). In this frequency band, patients with schizophrenia showed significantly increased functional connections between the bilateral cuneus and right supplementary motor area, reduced connections within the basal ganglia, and reduced connections between the dorsal striatum and left supplementary motor area. The dysfunction of the frontal gyrus significantly correlated with the dysfunction of the basal ganglia. Notably, these altered connections were significantly correlated with symptom severity. Our results demonstrate that frequency-selective altered corticostriatal-thalamo-cortical circuits in patients with schizophrenia are associated with symptoms severity.