Assessing Brain Metabolism With 7-T Proton Magnetic Resonance Spectroscopy in Patients With First-Episode Psychosis

Abstract

Can localized magnetic resonance spectroscopy performed at 7 T detect metabolic changes early in the course of a first-episode psychosis, and are these associated with neuropsychological performance? Eighty-one patients with first-episode psychosis were compared to 91 age-matched control participants; decreased levels of N -acetylaspartate were found in several brain regions, as well as selective regional decreases in glutamate, glutathione and γ-aminobutyric acid. Multiple metabolic abnormalities can be detected by 7-T magnetic resonance spectroscopy in patients with first-episode psychosis, which correlated with performance on neuropsychological tests. The use of high-field magnetic resonance spectroscopy (MRS) in multiple brain regions of a large population of human participants facilitates in vivo study of localized or diffusely altered brain metabolites in patients with first-episode psychosis (FEP) compared to healthy participants. To compare metabolite levels in 5 brain regions between patients with FEP (evaluated within 2 years of onset) and healthy controls, and to explore possible associations between targeted metabolite levels and neuropsychological test performance. Cross-sectional design used 7-T MRS at a research MR imaging facility in participants recruited from clinics at the Johns Hopkins Schizophrenia Center and the local population. Eighty-one patients who had received a DSM-IV diagnosis of FEP within the last 2 years and 91 healthy age-matched (but not sex-matched) volunteers participated. Brain metabolite levels including glutamate, glutamine, γ-aminobutyric acid (GABA), N -acetylaspartate, N -acetylaspartyl glutamate, and glutathione, as well as performance on neuropsychological tests. The mean (SD) age of 81 patients with FEP was 22.3 (4.4) years and 57 were male, while the mean (SD) age of 91 healthy participants was 23.3 (3.9) years and 42 were male. Compared with healthy participants, patients with FEP had lower levels of glutamate ( F 1,162 =  8.63, P  = .02), N -acetylaspartate ( F 1,161 =  5.93, P  = .03), GABA ( F 1,163 =  6.38, P  = .03), and glutathione ( F 1,162 =  4.79, P  = .04) in the anterior cingulate (all P values are corrected for multiple comparisons); lower levels of N -acetylaspartate in the orbitofrontal region ( F 1,136 =  7.23, P  = .05) and thalamus ( F 1,133 =  6.78, P  = .03); and lower levels of glutathione in the thalamus ( F 1,135 =  7.57, P  = .03). Among patients with FEP, N -acetylaspartate levels in the centrum semiovale white matter were significantly correlated with performance on neuropsychological tests, including processing speed ( r  = 0.48; P  < .001), visual ( r  = 0.33; P  = .04) and working ( r  = 0.38; P  = .01) memory, and overall cognitive performance ( r  = 0.38; P  = .01). Seven-tesla MRS offers insights into biochemical changes associated with FEP and may be a useful tool for probing brain metabolism that ranges from neurotransmission to stress-associated pathways in participants with psychosis. This cross-sectional study evaluates whether 7-T magnetic resonance spectroscopy is a useful tool for assessing brain metabolite levels in regions salient to psychosis, and explores the association exists between regional metabolite levels and neuropsychological test performance among healthy participants and patients with first-episode psychosis.