Failure to suppress default-mode network (DMN) activity during tasks and reduced anti-correlations between DMN and other brain networks at rest has been observed in various psychiatric disorders. However, the molecular mechanisms underlying this phenomenon are poorly understood. It has been shown that the neurotransmitter concentrations in DMN modulate the brain functional activities and connectivities in the healthy brain. In the current study, it was observed that the relationship between DMN neurotransmitter concentrations and the activities of brain functional network breaks down in first-episode psychosis patients. This finding provides opportunities for developing novel treatment strategies and earlier interventions for psychosis.