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

Abstract

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.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Schretlen reported receiving royalties on sales of a test used in the present study under an agreement with Psychological Assessment Resources, Inc, which has been reviewed and approved by Johns Hopkins University in accordance with its conflict of interest policies. No other disclosures were reported.

Figures

Figure 1.. Magnetic Resonance Spectroscopy (MRS) Voxel Localizations and Representative Spectra

A, Axial and sagittal T1-weighted images showing the locations of the 5 brain regions (red boxes) used for MRS in a healthy participant. B-D, Sample MRS spectra from a healthy participant with LCModel fitting output (heavy red lines) superimposed on the original data (black lines) are shown for the centrum semiovale (CSO) (B), dorsolateral prefrontal cortex (DLPFC) (C), and anterior cingulate cortex (ACC) (D). The residual signals following fitting are shown at the top of each panel. LCModel estimated baselines are shown by the gray lines. GABA indicates γ-aminobutyric acid; Gln, glutamine; Glu, glutamate, Glx, glutamate plus glutamine; GSH, glutathione; IU, institutional units; L, left; Lac, lactate; Lip, lipid; NAA, N-acetylaspartate; NAAG, N-acetylaspartyl glutamate; ml, myo-inositol; OFR, orbital frontal cortex; R, right; tCho, phosphocholine plus glycerophosphocholine; tCr, creatine plus phosphocreatine; and Thal, thalamus.

Figure 2.. Selected Metabolite Levels in 5 Brain Regions of Patients With First-Episode Psychosis (FEP) and Healthy Control (HC) Participants

Values represent means and SDs. Abbreviations are defined in the legend to Figure 1. aSignificant differences after correcting for the false-discovery rate.

Figure 3.. Magnetic Resonance Spectrographic Voxel Composition Expressed as Fractions of Gray Matter (GM), White Matter (WM), and Cerebrospinal Fluid (CSF) in the 5 Brain Regions Examined

Values represent means and SDs. No significant differences in voxel composition are found between participants with first-episode psychosis (FEP) and healthy control (HC) participants. ACC indicates anterior cingulate cortex; CSO, centrum semiovale, DLPFC, dorsolateral prefrontal cortex; OFR, orbital frontal cortex; and Thal, thalamus.