Association of default-mode network neurotransmitters and inter-network functional connectivity in first episode psychosis.

Abstract

Multiple psychiatric disorders are characterized by a failure to suppress default-mode network (DMN) activity during tasks and by weaker anti-correlations between DMN and other brain networks at rest. However, the cellular and molecular mechanisms underlying this phenomenon are poorly understood. At the cellular level, neuronal activity is regulated by multiple neurochemical processes including cycling of glutamate and GABA, the major excitatory and inhibitory neurotransmitters in brain. By combining functional MRI and magnetic resonance spectroscopy techniques, it has been shown that the neurotransmitter concentrations in DMN modulate not only functional activity during cognitive tasks, but also the functional connectivity between DMN and other brain networks such as frontoparietal executive control network (CN) at rest in the healthy brain. In the current study, we extend previous research to first episode psychosis (FEP) patients and their relatives. We detected higher glutamate (Glu) levels in the medial prefrontal cortex (MPFC) in FEP compared to healthy controls without a significant difference in GABA. We also observed a significantly lower functional anti-correlated connectivity between critical nodes within the DMN (MPFC) and CN (DLPFC) in FEP. Furthermore, the relationship between MPFC Glu and GABA concentrations and the functional anti-correlation that is seen in healthy people was absent in FEP patients. These findings imply that both the DMN Glu level and the interaction between DMN and CN are affected by the illness, as is the association between neurochemistry and functional connectivity. A better understanding of this observation could provide opportunities for developing novel treatment strategies for psychosis.