Group Differences of Multiregion Glutamate Concentration in Clinical High Risk and Schizophrenia

Glutamatergic changes are one of the characteristic features of psychotic disorders, with changes reported in their clinical high-risk states (CHR), first episode psychosis (FEP), and schizophrenia. Despite the abundance of literature using proton magnetic resonance (¹H-MRS) to quantify glutamate, the general pattern of changes across different brain regions is not well studied. We investigated the presence of diagnosis group effects on glutamate concentrations in 99 participants in the left dorsal lateral prefrontal cortex, anterior cingulate cortex, associative striatum, and hippocampus using ¹H-MRS in individuals with CHR (n = 31), schizophrenia spectrum psychotic disorder individuals (SCZ) with minimal antipsychotic exposure (n = 30), and healthy controls (n = 38). ¹H-MRS data were normalized against white matter, gray matter, and cerebrospinal fluid fractions within regions of interest (ROI) to quantify local glutamate concentration. Our results showed no significant group differences in glutamate concentration across the four ROIs. Exploratory analyses showed a significant relationship between region and positive symptom severity on glutamate concentration. Post hoc regression analyses revealed that higher positive symptom severity was significantly associated with higher hippocampal glutamate concentrations. We conclude that glutamate concentrations may be related to positive symptoms.