Associations between corticolimbic glutamatergic metabolites and functional connectivity in people at clinical high-risk for psychosis
Increased risk for psychosis is linked to altered relationships between corticolimbic connectivity and glutamatergic function, but the clinical implications remain uncertain due to the small sample size.
Where it sits
this study against the rest of the pnc-27 corpusSummary and findings
This study measured Glx (glutamate + glutamine) levels in the anterior cingulate cortex and hippocampus in antipsychotic-naïve participants at clinical high-risk for psychosis, comparing them to healthy controls and first-episode psychosis participants. The findings indicated significant interactions between group and ACC Glx for functional connectivity between specific brain regions. No significant Glx differences were found between the clinical high-risk group and healthy controls.
Abstract
Recent evidence suggests that psychosis involves glutamatergic dysfunction and altered activity/connectivity within corticolimbic circuitry. While altered relationships between corticolimbic glutamatergic metabolite levels and resting-state functional connectivity (FC) have been described in schizophrenia and first-episode psychosis (FEP), whether these disruptions are also present prior to psychosis onset remains unclear. We measured Glx (glutamate + glutamine) levels in the anterior cingulate cortex (ACC) and hippocampus with magnetic resonance spectroscopy (MRS), and resting-state FC between corticolimbic regions of interest (ACC, hippocampus, amygdala and nucleus accumbens (NAc)) in antipsychotic-naïve participants at clinical high-risk for psychosis (CHR-P, n=22), compared to healthy controls (HC, n=23) and FEP participants (n=10). Primary analyses compared corticolimbic Glx-FC interactions between CHR-P and HC groups. FEP individuals were included in secondary Glx comparisons but were excluded from FC analyses due to insufficient sample size after quality control. There was a significant interaction between group and ACC Glx for FC between the NAc and the bilateral amygdala and hippocampus (p-FDR=0.021), which was driven by a significant negative association in the CHR-P group (p-FDR=0.005). Complementary seed-to-whole-brain analyses revealed additional negative associations between ACC Glx and FC with the left middle temporal gyrus, and between hippocampal Glx and FC with the parahippocampal and temporal fusiform cortices in CHR-P individuals, which were absent in HC. FEP showed higher Glx than HC across both regions (p=0.015), but there were no significant Glx differences between CHR-P and HC. These data suggest that increased risk for psychosis is associated with altered relationships between corticolimbic connectivity and glutamatergic function.