S172. GLUTAMATE RELATED CONNECTIVITY DISTURBANCES OF THE SALIENCE AND DEFAULT MODE NETWORKS IN PSYCHOSIS

BACKGROUND: Cortical dysconnectivity and dysfunctional glutamatergic signalling are both implicated in the pathophysiology of psychotic illness. The relationship between these two systems, and the relevance to psychotic disorders remains unknown. METHODS: 50 individuals with a psychotic disorder and 54 healthy controls received baseline imaging using 1H-MRS to measure anterior cingulate glutamate concentrations, and resting state MRI to characterise functional brain networks. These measures were subsequently repeated following 3 days treatment with either the glutamatergic regulator riluzole (N=36), or a dopamine antagonist (N=14). The network-based statistic was used to examine relationships between glutamate concentrations and connectivity of the salience and default mode networks in patients and controls, and to investigate how this changed following pharmacological manipulation. RESULTS: In healthy controls higher baseline anterior cingulate glutamate concentrations were associated with reduced salience network connectivity, particularly for interhemispheric connections. This pattern was not seen in patients, and the greater the divergence from the relationship observed in controls, the greater the severity of negative symptoms. Default mode-salience internetwork connectivity was greater in patients compared to controls, and inversely correlated with baseline glutamate concentrations. Furthermore, riluzole associated changes in glutamate concentrations were associated with an inverse change in internetwork connectivity suggesting a causal relationship. DISCUSSION: Individuals with a psychotic disorder showed marked alterations in the relationship between anterior cingulate cortex glutamate concentration and connectivity of the salience and default mode networks. A pharmacological challenge with a glutamate regulating agent modulated this association, highlighting that the relationship is potentially malleable.