7T Proton Magnetic Resonance Spectroscopy of the Anterior Cingulate Cortex in First-Episode Schizophrenia

Abstract

Recent magnetic resonance spectroscopy (MRS) studies suggest that abnormalities of the glutamatergic system in schizophrenia may be dependent on illness stage, medication status, and symptomatology. Glutamatergic metabolites appear to be elevated in the prodromal and early stages of schizophrenia but unchanged or reduced below normal in chronic, medicated patients. However, few of these studies have measured metabolites with high-field 7T MR scanners, which offer higher signal-to-noise ratio and better spectral resolution than 3T scanners and facilitate separation of glutamate and glutamine into distinct signals. In this study, we examined glutamate and other metabolites in the dorsal anterior cingulate cortex (ACC) of first-episode schizophrenia patients. Glutamate and N-acetylaspartate (NAA) were significantly lower in schizophrenia patients vs controls. No differences were observed in levels of glutamine, GABA, or other metabolites. In schizophrenia patients but not controls, GABA was negatively correlated with the total score on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) as well as the immediate memory and language subscales. Our findings suggest that glutamate and NAA reductions in the ACC may be present early in the illness, but additional large-scale studies are needed to confirm these results as well as longitudinal studies to determine the effect of illness progression and treatment. The correlation between GABA and cognitive function suggests that MRS may be an important technique for investigating the neurobiology underlying cognitive deficits in schizophrenia.

Early treatment response in first episode psychosis: a 7-T magnetic resonance spectroscopic study of glutathione and glutamate

“…This is the first study to use ultrahigh-field 7T MRS to investigate the role of glutamate and GSH in early treatment response, and the first 7T MRS study on minimally medicated FEP subjects. A previous 7T MRS study included FEP subjects with an average of 55 weeks of antipsychotic exposure [54], compared with 6 days of median exposure in our sample. A more recent study [23] included FEP subjects with up to 2 years of illness duration, while we recruited all subjects during the acute first episode (mean SOFAS score of 38.1).…”

Dopamine and glutamate in schizophrenia: biology, symptoms and treatment

“…Higher field strength has greater sensitivity, enabling greater separation of glutamate and glutamine peaks, and allowing for more accurate quantification. Two studies in first‐episode patients have shown reduced glutamate concentrations in the anterior cingulate cortex, while another only found this in a subset of patients with predominantly negative symptoms. No difference has been observed in several other investigations.…”

Cognition and Related Neural Findings on Methamphetamine Use Disorder: Insights and Treatment Implications From Schizophrenia Research

“…Metabolic alteration of the ACC is also associated with impaired inhibitory control in both disorders, which is measured by levels of N-acetylaspartate, a marker of neuronal integrity (144). Reduced N-acetylaspartate levels in the ACC are observed in meth use disorder (145) and schizophrenia (146)(147)(148)(149). N-acetylaspartate levels correlate with poorer attention and inhibition in adult (68) and adolescent (37) meth users, and people with schizophrenia (150)(151)(152).…”

“…N-acetylaspartate levels correlate with poorer attention and inhibition in adult (68) and adolescent (37) meth users, and people with schizophrenia (150)(151)(152). Interestingly, reduced N-acetylaspartate in ACC is more dramatic with early onset of meth use (37), and reduced ACC levels of N-acetylaspartate are present at the early stages of schizophrenia (149), and in highrisk offspring of schizophrenia patients (152).…”