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Original Investigation
January 9, 2019

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

Author Affiliations
  • 1Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland
  • 2Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland
  • 3Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland
  • 4Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland
  • 5Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
  • 6Kennedy Krieger Institute, Baltimore, Maryland
JAMA Psychiatry. Published online January 9, 2019. doi:10.1001/jamapsychiatry.2018.3637
Key Points

Question  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?

Findings  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.

Meaning  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.


Importance  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.

Objective  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.

Design, Setting, and Participants  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.

Main Outcomes and Measures  Brain metabolite levels including glutamate, glutamine, γ-aminobutyric acid (GABA), N-acetylaspartate, N-acetylaspartyl glutamate, and glutathione, as well as performance on neuropsychological tests.

Results  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 (F1,162= 8.63, P = .02), N-acetylaspartate (F1,161= 5.93, P = .03), GABA (F1,163= 6.38, P = .03), and glutathione (F1,162= 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 (F1,136= 7.23, P = .05) and thalamus (F1,133= 6.78, P = .03); and lower levels of glutathione in the thalamus (F1,135= 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).

Conclusions and Relevance  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.