Brain glutamate concentration in men with early psychosis: a magnetic resonance spectroscopy case–control study at 7 T

Abstract

Abnormalities in glutamate neurotransmission are linked to psychotic symptoms and cognitive dysfunction in schizophrenia. magnetic resonance spectroscopy (MRS) provides an acceptable means of measuring glutamate in the human brain but findings from patient studies at conventional magnetic field strength show considerable heterogeneity. Ultra-high-field MRS offers greater precision in glutamate measurement, particularly in delineation of glutamate from its precursor and metabolite, glutamine. This study aimed to use high-field (7 T) MRS to measure concentrations of glutamate and glutamine in three brain regions, anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC) and putamen (PUT), in young men with early psychosis. MRS was performed in 17 male participants with early psychosis and 18 healthy age-matched controls. Neurometabolite levels were calculated with unsuppressed water signal as the reference and corrected for individual grey matter, white matter and cerebrospinal fluid concentration. Cognitive function was measured with the Brief Assessment of Cognition in Schizophrenia (BACS). Compared to controls, patients with early psychosis had lower concentrations of glutamate and glutamine in ACC. No differences were apparent in the DLPFC and PUT. In patients with early psychosis, there was a highly significant correlation between glutamate concentration in ACC and performance on the BACS, though the numbers available for this analysis were small. Our finding of lower glutamate levels in ACC in patients with schizophrenia is consistent with a recent meta-analysis of 7 T studies and suggests that this abnormality is present in both patients with early psychosis and those with longer-established illness. The possible link between ACC glutamate and cognitive performance requires replication in larger studies.

Basal glutamate in the hippocampus and the dorsolateral prefrontal cortex in schizophrenia: Relationships to cognitive proficiency investigated with structural equation modeling

“…Consistent with several (including recent 7 Tesla) ¹H MRS studies [25,[48][49][50][51], basal Glu levels from the dlPFC were not significantly different between SCZ and HC. However, basal Glu and myo-Inositol levels from the hippocampus were significantly lower in SCZ.…”

Is There a Glutathione Centered Redox Dysregulation Subtype of Schizophrenia?

“…This small but significant GSH reduction in schizophrenia has been reported by 2 other meta-analyses, one restricted to ultra-high field 7T MRS studies (effect size = 0.21) [66] and the other including all central measures of GSH MRS, CSF and post-mortem samples (effect size = 0.26) [67]. Since 2018, several MRS studies on ACC GSH in schizophrenia have been published [68][69][70][71][72][73][74] (Table 1). While the largest study to date supports Das and colleagues' report of GSH reduction in early stages of schizophrenia, smaller studies find no differences in patients when compared to healthy controls.…”

Schizophrenia Increases Variability of the Central Antioxidant System: A Meta-Analysis of Variance From MRS Studies of Glutathione

“…A total of 17 studies were identified by literature search [one with two eligible contrasts (20) and one with three eligible contrasts (21), making a total of 20 datasets] in schizophrenia (6,15,(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34). All these studies were published between 2001 and 2021, and included a total of 589 patients and 601 controls.…”