Short-term Medication Effects on Brain Functional Activity and Network Architecture in First-Episode psychosis: a longitudinal fMRI study

The effect of antipsychotic medications is critical for the long-term outcome of symptoms and functions during first-episode psychosis (FEP). However, how brain functions respond to the antipsychotic treatment in the early stage of psychosis and its underlying neural mechanisms remain unclear. In this study, we explored the cross-sectional and longitudinal changes of regional homogeneity (ReHo), whole-brain functional connectivity, and network topological properties via resting-state functional magnetic resonance images. Thirty-two drug-naïve FEP patients and 30 matched healthy volunteers (HV) were included, where 23 patients were re-visited with effective responses after two months of antipsychotic treatment. Compared to HV, drug-naive patients demonstrated significantly different patterns of functional connectivity involving the right thalamus. These functional alterations mainly involved decreased ReHo, increased nodal efficiency in the right thalamus, and increased thalamic-sensorimotor-frontoparietal connectivity. In the follow-up analysis, patients after treatment showed reduced ReHo and nodal clustering in visual networks, as well as disturbances of visual-somatomotor and hippocampus-superior frontal gyrus connectivity. The longitudinal changes of ReHo in the visual cortex were associated with an improvement in general psychotic symptoms. This study provides new evidence regarding alterations in brain function linked to schizophrenia onset and affected by antipsychotic medications. Moreover, our results demonstrated that the functional alterations at baseline were not fully modulated by antipsychotic medications, suggesting that antipsychotic medications may reduce psychotic symptoms but limit the effects in regions involved in disease pathophysiology.